PharmaCoNets

PharmaCoNets of Loperamide (S_PCN: 106.31 )

Loperamide regulated-network (S_DN: 21.65)

Drug Name

Pathway ID

Pathway name

P-value

No. of gene members

UniProt AC

Gene name

Detail of Coexpression

Loperamide

hsa00052

Galactose metabolism

1.03E-02

P06280, O43451

GLA, MGAM

Loperamide

hsa00053

Ascorbate and aldarate metabolism

4.93E-02

P14550

AKR1A1

Loperamide

hsa00071

Fatty acid degradation

4.66E-02

O75521, P11766, P33121

ECI2, ADH5, ACSL1

Loperamide

hsa00190

Oxidative phosphorylation

2.29E-02

Q16718, O14521

NDUFA5, SDHD

Loperamide

hsa00230

Purine metabolism

4.60E-02

Q13370, P36959, Q13956, P27707

PDE3B, GMPR, PDE6H, DCK

Loperamide

hsa00240

Pyrimidine metabolism

4.50E-02

P32320, P27707

CDA, DCK

Loperamide

hsa00500

Starch and sucrose metabolism

9.77E-06

O43451, P46976, P35573, P06737

MGAM, GYG1, AGL, PYGL

Loperamide

hsa00520

Amino sugar and nucleotide sugar metabolism

2.24E-02

Q16222, Q9Y223, P06865

UAP1, GNE, HEXA

Loperamide

hsa00533

Glycosaminoglycan biosynthesis - keratan sulfate

3.43E-02

Q9NY97

B3GNT2

Loperamide

hsa00534

Glycosaminoglycan biosynthesis - heparan sulfate / heparin

4.77E-02

Q7LGA3

HS2ST1

Loperamide

hsa00565

Ether lipid metabolism

4.93E-02

Q8N661

TMEM86B

Loperamide

hsa00590

Arachidonic acid metabolism

3.85E-02

P11712, P09960

CYP2C9, LTA4H

Loperamide

hsa00591

Linoleic acid metabolism

4.07E-02

P11712

CYP2C9

Loperamide

hsa00670

One carbon pool by folate

3.99E-02

O95954, Q99707

FTCD, MTR

Loperamide

hsa00730

Thiamine metabolism

7.19E-04

P05186, P24666

ALPL, ACP1

Loperamide

hsa00770

Pantothenate and CoA biosynthesis

2.26E-04

O95498, O95497, Q9NRN7

VNN2, VNN1, AASDHPPT

Loperamide

hsa00920

Sulfur metabolism

3.01E-02

O95571

ETHE1

Loperamide

hsa00970

Aminoacyl-tRNA biosynthesis

1.58E-04

O95363, P54136, P14868, Q15046

FARS2, RARS1, DARS, KARS

Loperamide

hsa00980

Metabolism of xenobiotics by cytochrome P450

9.14E-03

P78417, P11712

GSTO1, CYP2C9

Loperamide

hsa00982

Drug metabolism - cytochrome P450

9.14E-03

P11712, P78417

CYP2C9, GSTO1

Loperamide

hsa00983

Drug metabolism - other enzymes

8.82E-04

P20839, P32320, P05164, Q16772

IMPDH1, CDA, MPO, GSTA3

Loperamide

hsa01100

Metabolic pathways

3.95E-02

Q9Y234, Q99707, P29218, P11310, P27707, Q13370, P36959, Q13956, P30043, Q02252, O60701, O14772, O95954, Q02318, P04406, O15466, P09960, Q9P2R7, Q9UHY7, P35573, Q13488, Q16718, Q02809

LIPT1, MTR, IMPA1, ACADM, DCK, PDE3B, GMPR, PDE6H, BLVRB, ALDH6A1, UGDH, FPGT, FTCD, CYP27A1, GAPDH, ST8SIA5, LTA4H, SUCLA2, ENOPH1, AGL, TCIRG1, NDUFA5, PLOD1

Loperamide

hsa01524

Platinum drug resistance

1.97E-04

P10415, Q13489, O15392, P78417, P23025, P11388, P43246

BCL2, BIRC3, BIRC5, GSTO1, XPA, TOP2A, MSH2

Loperamide

hsa02010

ABC transporters

1.99E-04

P45844, P08183, Q8IZY2, Q99758

ABCG1, ABCB1, ABCA7, ABCA3

Loperamide

hsa03008

Ribosome biogenesis in eukaryotes

2.60E-03

Q9NYH9, P78345, Q9BVP2, O15381, Q9GZY0

UTP6, RPP38, GNL3, NVL, NXF2; NXF2B

Loperamide

hsa03013

RNA transport

1.14E-05

P62826, O14980, P52298, Q09161, O14893, P61326, Q7Z3B4, P35658, P63279, Q14152, O75822, P78345, Q14240, Q9Y6A5, P51114

RAN, XPO1, NCBP2, NCBP1, GEMIN2, MAGOH, NUP54, NUP214, UBE2I, EIF3A, EIF3J, RPP38, EIF4A2, TACC3, FXR1

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P05976	MYL1	Myosin light chain 1/3, skeletal muscle isoform	P62826	RAN	GTP-binding nuclear protein Ran	0.715
P21462	FPR1	fMet-Leu-Phe receptor	O14980	XPO1	Exportin-1	-0.742
P22748	CA4	Carbonic anhydrase 4	P52298	NCBP2	Nuclear cap-binding protein subunit 2	-0.879
P21462	FPR1	fMet-Leu-Phe receptor	P52298	NCBP2	Nuclear cap-binding protein subunit 2	-0.874
P51684	CCR6	C-C chemokine receptor type 6	P52298	NCBP2	Nuclear cap-binding protein subunit 2	0.924
P21462	FPR1	fMet-Leu-Phe receptor	Q09161	NCBP1	Nuclear cap-binding protein subunit 1	-0.78
P22748	CA4	Carbonic anhydrase 4	O14893	GEMIN2	Gem-associated protein 2	-0.709
P21462	FPR1	fMet-Leu-Phe receptor	O14893	GEMIN2	Gem-associated protein 2	-0.87
P51684	CCR6	C-C chemokine receptor type 6	O14893	GEMIN2	Gem-associated protein 2	0.771
P22748	CA4	Carbonic anhydrase 4	P61326	MAGOH	Protein mago nashi homolog	-0.822
P21462	FPR1	fMet-Leu-Phe receptor	P61326	MAGOH	Protein mago nashi homolog	-0.835
P51684	CCR6	C-C chemokine receptor type 6	P61326	MAGOH	Protein mago nashi homolog	0.704
P22748	CA4	Carbonic anhydrase 4	Q7Z3B4	NUP54	Nucleoporin p54	-0.776
P21462	FPR1	fMet-Leu-Phe receptor	Q7Z3B4	NUP54	Nucleoporin p54	-0.903
P51684	CCR6	C-C chemokine receptor type 6	Q7Z3B4	NUP54	Nucleoporin p54	0.811
P22748	CA4	Carbonic anhydrase 4	P35658	NUP214	Nuclear pore complex protein Nup214	0.827
P21462	FPR1	fMet-Leu-Phe receptor	P35658	NUP214	Nuclear pore complex protein Nup214	0.971
P05976	MYL1	Myosin light chain 1/3, skeletal muscle isoform	P63279	UBE2I	SUMO-conjugating enzyme UBC9	0.742
P22748	CA4	Carbonic anhydrase 4	Q14152	EIF3A	Eukaryotic translation initiation factor 3 subunit A	-0.786
P21462	FPR1	fMet-Leu-Phe receptor	Q14152	EIF3A	Eukaryotic translation initiation factor 3 subunit A	-0.89
P51684	CCR6	C-C chemokine receptor type 6	Q14152	EIF3A	Eukaryotic translation initiation factor 3 subunit A	0.701
P22748	CA4	Carbonic anhydrase 4	O75822	EIF3J	Eukaryotic translation initiation factor 3 subunit J	-0.869
P21462	FPR1	fMet-Leu-Phe receptor	O75822	EIF3J	Eukaryotic translation initiation factor 3 subunit J	-0.953
P51684	CCR6	C-C chemokine receptor type 6	O75822	EIF3J	Eukaryotic translation initiation factor 3 subunit J	0.711
P22748	CA4	Carbonic anhydrase 4	P78345	RPP38	Ribonuclease P protein subunit p38	-0.731
P51684	CCR6	C-C chemokine receptor type 6	P78345	RPP38	Ribonuclease P protein subunit p38	0.861
P21462	FPR1	fMet-Leu-Phe receptor	Q14240	EIF4A2	Eukaryotic initiation factor 4A-II	-0.721
P22748	CA4	Carbonic anhydrase 4	Q9Y6A5	TACC3	Transforming acidic coiled-coil-containing protein 3	0.912
P21462	FPR1	fMet-Leu-Phe receptor	Q9Y6A5	TACC3	Transforming acidic coiled-coil-containing protein 3	0.904
P51684	CCR6	C-C chemokine receptor type 6	Q9Y6A5	TACC3	Transforming acidic coiled-coil-containing protein 3	-0.732
P21462	FPR1	fMet-Leu-Phe receptor	P51114	FXR1	Fragile X mental retardation syndrome-related protein 1	-0.713

Loperamide

hsa03015

mRNA surveillance pathway

3.62E-02

O43148, P61326, P52298

RNMT, MAGOH, NCBP2

Loperamide

hsa03018

RNA degradation

5.00E-02

Q9NQT4

EXOSC5

Loperamide

hsa03020

RNA polymerase

9.86E-07

Q9GZM3, P52435

POLR2J2, POLR2J

Loperamide

hsa03022

Basal transcription factors

3.32E-02

O00268, Q15544

TAF4, TAF11

Loperamide

hsa03040

Spliceosome

2.95E-09

Q14562, O43143, O60508, Q99633, P17844, O14776, P08579, O75940, P52298, P09651, Q15365, O75494, Q13595, Q07955, Q01130, Q13243, Q9UMS4, P11142, O95777, O43447, P61326

DHX8, DHX15, CDC40, PRPF18, DDX5, TCERG1, SNRPB2, SMNDC1, NCBP2, HNRNPA1, PCBP1, FUSIP1, TRA2A, SFRS1, SFRS2, SFRS5, PRPF19, HSPA8, LSM8, PPIH, MAGOH

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P0DP23	CALM1	Calmodulin-1	Q14562	DHX8	ATP-dependent RNA helicase DHX8	0.942
P46091	GPR1	Chemerin-like receptor 2	Q14562	DHX8	ATP-dependent RNA helicase DHX8	-0.819
P0DP25	CALM3	Calmodulin-3	Q14562	DHX8	ATP-dependent RNA helicase DHX8	0.942
P0DP24	CALM2	Calmodulin-2	Q14562	DHX8	ATP-dependent RNA helicase DHX8	0.942
P0DP23	CALM1	Calmodulin-1	O43143	DHX15	ATP-dependent RNA helicase DHX15	0.963
P46091	GPR1	Chemerin-like receptor 2	O43143	DHX15	ATP-dependent RNA helicase DHX15	-0.816
P0DP25	CALM3	Calmodulin-3	O43143	DHX15	ATP-dependent RNA helicase DHX15	0.963
P0DP24	CALM2	Calmodulin-2	O43143	DHX15	ATP-dependent RNA helicase DHX15	0.963
P0DP23	CALM1	Calmodulin-1	O60508	CDC40	Pre-mRNA-processing factor 17	0.828
P46091	GPR1	Chemerin-like receptor 2	O60508	CDC40	Pre-mRNA-processing factor 17	-0.778
P0DP25	CALM3	Calmodulin-3	O60508	CDC40	Pre-mRNA-processing factor 17	0.828
P0DP24	CALM2	Calmodulin-2	O60508	CDC40	Pre-mRNA-processing factor 17	0.828
P46091	GPR1	Chemerin-like receptor 2	Q99633	PRPF18	Pre-mRNA-splicing factor 18	-0.711
P0DP24	CALM2	Calmodulin-2	P17844	DDX5	Probable ATP-dependent RNA helicase DDX5	0.734
O15182	CETN3	Centrin-3	O14776	TCERG1	Transcription elongation regulator 1	0.758
P0DP23	CALM1	Calmodulin-1	P08579	SNRPB2	U2 small nuclear ribonucleoprotein B''	0.781
P0DP25	CALM3	Calmodulin-3	P08579	SNRPB2	U2 small nuclear ribonucleoprotein B''	0.781
P0DP24	CALM2	Calmodulin-2	P08579	SNRPB2	U2 small nuclear ribonucleoprotein B''	0.781
O15182	CETN3	Centrin-3	O75940	SMNDC1	Survival of motor neuron-related-splicing factor 30	0.859
O15182	CETN3	Centrin-3	P52298	NCBP2	Nuclear cap-binding protein subunit 2	0.701
O15182	CETN3	Centrin-3	P09651	HNRNPA1	Heterogeneous nuclear ribonucleoprotein A1	0.757
P0DP24	CALM2	Calmodulin-2	Q15365	PCBP1	Poly(rC)-binding protein 1	0.75
O15182	CETN3	Centrin-3	O75494	FUSIP1	Serine/arginine-rich splicing factor 10	0.85
P46091	GPR1	Chemerin-like receptor 2	Q13595	TRA2A	Transformer-2 protein homolog alpha	-0.753
P0DP23	CALM1	Calmodulin-1	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	0.914
P0DP25	CALM3	Calmodulin-3	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	0.914
P0DP24	CALM2	Calmodulin-2	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	0.914
P0DP23	CALM1	Calmodulin-1	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	0.841
P46091	GPR1	Chemerin-like receptor 2	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	-0.746
P0DP25	CALM3	Calmodulin-3	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	0.841
P0DP24	CALM2	Calmodulin-2	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	0.841
P0DP23	CALM1	Calmodulin-1	Q13243	SFRS5	Serine/arginine-rich splicing factor 5	0.784
P0DP25	CALM3	Calmodulin-3	Q13243	SFRS5	Serine/arginine-rich splicing factor 5	0.784
P0DP24	CALM2	Calmodulin-2	Q13243	SFRS5	Serine/arginine-rich splicing factor 5	0.784
P46091	GPR1	Chemerin-like receptor 2	Q9UMS4	PRPF19	Pre-mRNA-processing factor 19	0.703
P0DP23	CALM1	Calmodulin-1	P11142	HSPA8	Heat shock cognate 71 kDa protein	0.804
P0DP25	CALM3	Calmodulin-3	P11142	HSPA8	Heat shock cognate 71 kDa protein	0.804
P0DP24	CALM2	Calmodulin-2	P11142	HSPA8	Heat shock cognate 71 kDa protein	0.804
O15182	CETN3	Centrin-3	O95777	LSM8	U6 snRNA-associated Sm-like protein LSm8	0.723
P0DP23	CALM1	Calmodulin-1	O43447	PPIH	Peptidyl-prolyl cis-trans isomerase H	0.748
P0DP25	CALM3	Calmodulin-3	O43447	PPIH	Peptidyl-prolyl cis-trans isomerase H	0.748
P0DP24	CALM2	Calmodulin-2	O43447	PPIH	Peptidyl-prolyl cis-trans isomerase H	0.748
O15182	CETN3	Centrin-3	P61326	MAGOH	Protein mago nashi homolog	0.811

Loperamide

hsa03050

Proteasome

5.53E-03

P43686, P28070

PSMC4, PSMB4

Loperamide

hsa03320

PPAR signaling pathway

2.18E-02

O00767, Q02318

SCD, CYP27A1

Loperamide

hsa03460

Fanconi anemia pathway

3.70E-03

Q9NPI8, O60673, Q9UNA4

FANCF, REV3L, POLI

Loperamide

hsa04014

Ras signaling pathway

2.65E-03

P31751, P20827, P49767, Q13009, P17252, Q15311, P0DP23, P62873, P19174

AKT2, EFNA1, VEGFC, TIAM1, PRKCA, RALBP1, CALM1, GNB1, PLCG1

Loperamide

hsa04015

Rap1 signaling pathway

3.68E-04

P20827, P49767, P63261, P25116, Q13009, Q08828, P51828, P31751, P0DP23, P17252, P19174

EFNA1, VEGFC, ACTG1, F2R, TIAM1, ADCY1, ADCY7, AKT2, CALM1, PRKCA, PLCG1

Loperamide

hsa04020

Calcium signaling pathway

7.15E-09

P27987, Q08828, Q16566, Q13557, P17252, O15399, P19174, P25116, P61073, P0DP23, P51828, P23634, P49767

ITPKB, ADCY1, CAMK4, CAMK2D, PRKCA, GRIN2D, PLCG1, F2R, CXCR4, CALM1, ADCY7, ATP2B4, VEGFC

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P0DP23	CALM1	Calmodulin-1	P27987	ITPKB	Inositol-trisphosphate 3-kinase B	0.701
P0DP25	CALM3	Calmodulin-3	P27987	ITPKB	Inositol-trisphosphate 3-kinase B	0.701
P0DP24	CALM2	Calmodulin-2	P27987	ITPKB	Inositol-trisphosphate 3-kinase B	0.701
P0DP23	CALM1	Calmodulin-1	Q08828	ADCY1	Adenylate cyclase type 1	0.725
P0DP24	CALM2	Calmodulin-2	Q08828	ADCY1	Adenylate cyclase type 1	0.711
P46091	GPR1	Chemerin-like receptor 2	Q16566	CAMK4	Calcium/calmodulin-dependent protein kinase type IV	0.865
P0DP24	CALM2	Calmodulin-2	Q13557	CAMK2D	Calcium/calmodulin-dependent protein kinase type II subunit delta	0.786
P0DP23	CALM1	Calmodulin-1	P17252	PRKCA	Protein kinase C alpha type	-0.776
P46091	GPR1	Chemerin-like receptor 2	P17252	PRKCA	Protein kinase C alpha type	0.741
P0DP25	CALM3	Calmodulin-3	P17252	PRKCA	Protein kinase C alpha type	-0.776
P0DP24	CALM2	Calmodulin-2	P17252	PRKCA	Protein kinase C alpha type	-0.776
P0DP23	CALM1	Calmodulin-1	O15399	GRIN2D	Glutamate receptor ionotropic, NMDA 2D	-0.764
P46091	GPR1	Chemerin-like receptor 2	O15399	GRIN2D	Glutamate receptor ionotropic, NMDA 2D	0.744
P0DP25	CALM3	Calmodulin-3	O15399	GRIN2D	Glutamate receptor ionotropic, NMDA 2D	-0.764
P0DP24	CALM2	Calmodulin-2	O15399	GRIN2D	Glutamate receptor ionotropic, NMDA 2D	-0.764
P0DP23	CALM1	Calmodulin-1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
P0DP25	CALM3	Calmodulin-3	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
P0DP24	CALM2	Calmodulin-2	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
P46091	GPR1	Chemerin-like receptor 2	P25116	F2R	Proteinase-activated receptor 1	0.76
P0DP24	CALM2	Calmodulin-2	P61073	CXCR4	C-X-C chemokine receptor type 4	0.759
P0DP23	CALM1	Calmodulin-1	P0DP23	CALM1	Calmodulin-1	1
P46091	GPR1	Chemerin-like receptor 2	P0DP23	CALM1	Calmodulin-1	-0.846
P0DP25	CALM3	Calmodulin-3	P0DP23	CALM1	Calmodulin-1	1
P0DP24	CALM2	Calmodulin-2	P0DP23	CALM1	Calmodulin-1	1
P0DP23	CALM1	Calmodulin-1	P51828	ADCY7	Adenylate cyclase type 7	0.719
P0DP23	CALM1	Calmodulin-1	P23634	ATP2B4	Plasma membrane calcium-transporting ATPase 4	0.793
P46091	GPR1	Chemerin-like receptor 2	P23634	ATP2B4	Plasma membrane calcium-transporting ATPase 4	-0.766
P0DP25	CALM3	Calmodulin-3	P23634	ATP2B4	Plasma membrane calcium-transporting ATPase 4	0.793
P0DP24	CALM2	Calmodulin-2	P23634	ATP2B4	Plasma membrane calcium-transporting ATPase 4	0.793
P0DP23	CALM1	Calmodulin-1	P49767	VEGFC	Vascular endothelial growth factor C	-0.84
P46091	GPR1	Chemerin-like receptor 2	P49767	VEGFC	Vascular endothelial growth factor C	0.718
P0DP25	CALM3	Calmodulin-3	P49767	VEGFC	Vascular endothelial growth factor C	-0.84
P0DP24	CALM2	Calmodulin-2	P49767	VEGFC	Vascular endothelial growth factor C	-0.84

Loperamide

hsa04024

cAMP signaling pathway

3.17E-04

Q08828, P51828, P31751, P0DP23, P23634, Q16566, Q13557, Q13370, O15399, P25116, Q13009

ADCY1, ADCY7, AKT2, CALM1, ATP2B4, CAMK4, CAMK2D, PDE3B, GRIN2D, F2R, TIAM1

Loperamide

hsa04061

Viral protein interaction with cytokine and cytokine receptor

4.48E-02

P09341, P19875, P25024, P25025, P14784

CXCL1, CXCL2, CXCR1, CXCR2, IL2RB

Loperamide

hsa04062

Chemokine signaling pathway

2.36E-05

P51684, P25024, P25025, P09341, P19875, Q8NHW4, P47992, Q9UBD3, P07948, P42338, P19174, P62873, P63218, P50151, P49407, Q08881, Q08828, P51828, Q13009, P14598, P42224, P31751, P49841

CCR6, CXCR1, CXCR2, CXCL1, CXCL2, CCL4L2, XCL1, XCL2, LYN, PIK3CB, PLCG1, GNB1, GNG5, GNG10, ARRB1, ITK, ADCY1, ADCY7, TIAM1, NCF1, STAT1, AKT2, GSK3B

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P0DP23	CALM1	Calmodulin-1	P51684	CCR6	C-C chemokine receptor type 6	-0.734
Q13547	HDAC1	Histone deacetylase 1	P25024	CXCR1	C-X-C chemokine receptor type 1	-0.803
P25024	CXCR1	C-X-C chemokine receptor type 1	P25024	CXCR1	C-X-C chemokine receptor type 1	1
Q13547	HDAC1	Histone deacetylase 1	P25025	CXCR2	C-X-C chemokine receptor type 2	-0.719
P25024	CXCR1	C-X-C chemokine receptor type 1	P25025	CXCR2	C-X-C chemokine receptor type 2	0.929
Q13547	HDAC1	Histone deacetylase 1	P09341	CXCL1	Growth-regulated alpha protein	-0.736
Q13547	HDAC1	Histone deacetylase 1	P19875	CXCL2	C-X-C motif chemokine 2	-0.862
P0DP23	CALM1	Calmodulin-1	Q8NHW4	CCL4L2	C-C motif chemokine 4-like	0.729
P25024	CXCR1	C-X-C chemokine receptor type 1	P47992	XCL1	Lymphotactin	-0.706
P25024	CXCR1	C-X-C chemokine receptor type 1	Q9UBD3	XCL2	Cytokine SCM-1 beta	-0.706
P0DP23	CALM1	Calmodulin-1	Q8NHW4	CCL4L2	C-C motif chemokine 4-like	0.729
P25024	CXCR1	C-X-C chemokine receptor type 1	P07948	LYN	Tyrosine-protein kinase Lyn	0.707
Q13547	HDAC1	Histone deacetylase 1	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.774
P0DP23	CALM1	Calmodulin-1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
P0DP23	CALM1	Calmodulin-1	P62873	GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	0.853
Q13547	HDAC1	Histone deacetylase 1	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	-0.864
P25024	CXCR1	C-X-C chemokine receptor type 1	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	0.727
Q13547	HDAC1	Histone deacetylase 1	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	-0.716
P25024	CXCR1	C-X-C chemokine receptor type 1	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	0.743
P25024	CXCR1	C-X-C chemokine receptor type 1	P49407	ARRB1	Beta-arrestin-1	-0.721
P25024	CXCR1	C-X-C chemokine receptor type 1	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.736
P0DP23	CALM1	Calmodulin-1	Q08828	ADCY1	Adenylate cyclase type 1	0.725
P0DP23	CALM1	Calmodulin-1	P51828	ADCY7	Adenylate cyclase type 7	0.719
P0DP23	CALM1	Calmodulin-1	Q13009	TIAM1	Rho guanine nucleotide exchange factor TIAM1	-0.788
P0DP23	CALM1	Calmodulin-1	P14598	NCF1	Neutrophil cytosol factor 1	0.854
P0DP23	CALM1	Calmodulin-1	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP23	CALM1	Calmodulin-1	P31751	AKT2	RAC-beta serine/threonine-protein kinase	0.761
P25024	CXCR1	C-X-C chemokine receptor type 1	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.823

Loperamide

hsa04064

NF-kappa B signaling pathway

2.69E-06

P10415, Q13489, P51617, Q13546, P14778, P01584, P29965, P19174, Q04759, Q9UDY8, Q13077, P06239, P24522, O75293, Q8NHW4, P09341, P19875, Q06643, Q9NQC7

BCL2, BIRC3, IRAK1, RIPK1, IL1R1, IL1B, CD40LG, PLCG1, PRKCQ, MALT1, TRAF1, LCK, GADD45A, GADD45B, CCL4L2, CXCL1, CXCL2, LTB, CYLD

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P0DP23	CALM1	Calmodulin-1	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P51684	CCR6	C-C chemokine receptor type 6	P10415	BCL2	Apoptosis regulator Bcl-2	0.84
P0DP25	CALM3	Calmodulin-3	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP24	CALM2	Calmodulin-2	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP23	CALM1	Calmodulin-1	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P0DP25	CALM3	Calmodulin-3	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P0DP24	CALM2	Calmodulin-2	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P0DP23	CALM1	Calmodulin-1	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P51684	CCR6	C-C chemokine receptor type 6	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	0.722
P0DP25	CALM3	Calmodulin-3	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P0DP24	CALM2	Calmodulin-2	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P51684	CCR6	C-C chemokine receptor type 6	Q13546	RIPK1	Receptor-interacting serine/threonine-protein kinase 1	-0.868
Q13547	HDAC1	Histone deacetylase 1	P14778	IL1R1	Interleukin-1 receptor type 1	-0.854
P0DP24	CALM2	Calmodulin-2	P01584	IL1B	Interleukin-1 beta	0.72
P0DP23	CALM1	Calmodulin-1	P29965	CD40LG	CD40 ligand	-0.721
P0DP25	CALM3	Calmodulin-3	P29965	CD40LG	CD40 ligand	-0.721
P0DP24	CALM2	Calmodulin-2	P29965	CD40LG	CD40 ligand	-0.721
P0DP23	CALM1	Calmodulin-1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
P0DP25	CALM3	Calmodulin-3	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
P0DP24	CALM2	Calmodulin-2	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
Q13547	HDAC1	Histone deacetylase 1	Q04759	PRKCQ	Protein kinase C theta type	0.723
P51684	CCR6	C-C chemokine receptor type 6	Q9UDY8	MALT1	Mucosa-associated lymphoid tissue lymphoma translocation protein 1	0.869
P51684	CCR6	C-C chemokine receptor type 6	Q13077	TRAF1	TNF receptor-associated factor 1	0.768
Q13547	HDAC1	Histone deacetylase 1	P06239	LCK	Tyrosine-protein kinase Lck	0.811
P51684	CCR6	C-C chemokine receptor type 6	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	-0.712
P0DP23	CALM1	Calmodulin-1	O75293	GADD45B	Growth arrest and DNA damage-inducible protein GADD45 beta	-0.853
P0DP25	CALM3	Calmodulin-3	O75293	GADD45B	Growth arrest and DNA damage-inducible protein GADD45 beta	-0.853
P0DP24	CALM2	Calmodulin-2	O75293	GADD45B	Growth arrest and DNA damage-inducible protein GADD45 beta	-0.853
P0DP23	CALM1	Calmodulin-1	Q8NHW4	CCL4L2	C-C motif chemokine 4-like	0.729
P0DP23	CALM1	Calmodulin-1	Q8NHW4	CCL4L2	C-C motif chemokine 4-like	0.729
Q13547	HDAC1	Histone deacetylase 1	P09341	CXCL1	Growth-regulated alpha protein	-0.736
Q13547	HDAC1	Histone deacetylase 1	P19875	CXCL2	C-X-C motif chemokine 2	-0.862
Q13547	HDAC1	Histone deacetylase 1	Q06643	LTB	Lymphotoxin-beta	0.74
P0DP23	CALM1	Calmodulin-1	Q9NQC7	CYLD	Ubiquitin carboxyl-terminal hydrolase CYLD	0.883
P0DP24	CALM2	Calmodulin-2	Q9NQC7	CYLD	Ubiquitin carboxyl-terminal hydrolase CYLD	0.778

Loperamide

hsa04070

Phosphatidylinositol signaling system

6.70E-05

P19174, P0DP23, Q14643, P23743, P48426, O14732, P27987, P17252

PLCG1, CALM1, ITPR1, DGKA, PIP4K2A, IMPA2, ITPKB, PRKCA

Loperamide

hsa04071

Sphingolipid signaling pathway

1.57E-06

P17252, Q9H228, P01375, Q13510, Q13362, Q16537, Q9BX95, Q16539, P04637, P10415, Q9UQC2, P01042

PRKCA, EDG8, TNF, ASAH1, PPP2R5C, PPP2R5E, SGPP1, MAPK14, TP53, BCL2, GAB2, KNG1

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P21462	FPR1	fMet-Leu-Phe receptor	P17252	PRKCA	Protein kinase C alpha type	-0.731
P51684	CCR6	C-C chemokine receptor type 6	P17252	PRKCA	Protein kinase C alpha type	0.738
P0DP24	CALM2	Calmodulin-2	P17252	PRKCA	Protein kinase C alpha type	-0.776
P22748	CA4	Carbonic anhydrase 4	Q9H228	EDG8	Sphingosine 1-phosphate receptor 5	-0.814
P08183	ABCB1	ATP-dependent translocase ABCB1	Q9H228	EDG8	Sphingosine 1-phosphate receptor 5	0.787
P21462	FPR1	fMet-Leu-Phe receptor	Q9H228	EDG8	Sphingosine 1-phosphate receptor 5	-0.716
P22748	CA4	Carbonic anhydrase 4	P01375	TNF	Tumor necrosis factor	0.744
P08183	ABCB1	ATP-dependent translocase ABCB1	P01375	TNF	Tumor necrosis factor	-0.769
P21462	FPR1	fMet-Leu-Phe receptor	P01375	TNF	Tumor necrosis factor	0.77
P0DP24	CALM2	Calmodulin-2	Q13510	ASAH1	Acid ceramidase	0.889
P22748	CA4	Carbonic anhydrase 4	Q13362	PPP2R5C	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform	-0.758
P21462	FPR1	fMet-Leu-Phe receptor	Q13362	PPP2R5C	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform	-0.878
P0DP24	CALM2	Calmodulin-2	Q13362	PPP2R5C	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform	0.765
P51684	CCR6	C-C chemokine receptor type 6	Q16537	PPP2R5E	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform	0.819
P22748	CA4	Carbonic anhydrase 4	Q9BX95	SGPP1	Sphingosine-1-phosphate phosphatase 1	-0.88
P21462	FPR1	fMet-Leu-Phe receptor	Q9BX95	SGPP1	Sphingosine-1-phosphate phosphatase 1	-0.932
P51684	CCR6	C-C chemokine receptor type 6	Q9BX95	SGPP1	Sphingosine-1-phosphate phosphatase 1	0.876
P22748	CA4	Carbonic anhydrase 4	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.767
P51684	CCR6	C-C chemokine receptor type 6	P04637	TP53	Cellular tumor antigen p53	0.728
P22748	CA4	Carbonic anhydrase 4	P10415	BCL2	Apoptosis regulator Bcl-2	-0.863
P21462	FPR1	fMet-Leu-Phe receptor	P10415	BCL2	Apoptosis regulator Bcl-2	-0.855
P51684	CCR6	C-C chemokine receptor type 6	P10415	BCL2	Apoptosis regulator Bcl-2	0.84
P0DP24	CALM2	Calmodulin-2	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P08183	ABCB1	ATP-dependent translocase ABCB1	Q9UQC2	GAB2	GRB2-associated-binding protein 2	-0.866
P0DP24	CALM2	Calmodulin-2	Q9UQC2	GAB2	GRB2-associated-binding protein 2	0.798
P0DP24	CALM2	Calmodulin-2	P01042	KNG1	Kininogen-1	-0.71

Loperamide

hsa04072

Phospholipase D signaling pathway

2.68E-03

P31751, P42338, P43657, P25024, P25025, P19174, P17252, Q15438, Q08828, P51828, P23743, P00734

AKT2, PIK3CB, P2RY5, CXCR1, CXCR2, PLCG1, PRKCA, PSCD1, ADCY1, ADCY7, DGKA, F2

Loperamide

hsa04120

Ubiquitin mediated proteolysis

3.44E-02

Q14145, Q13042, P62837, Q15751

KEAP1, CDC16, UBE2D2, HERC1

Loperamide

hsa04140

Autophagy - animal

2.58E-02

P31751, Q7L523, Q96RR4, O75460, P10415, Q96GC9, Q8TEV9

AKT2, RRAGA, CAMKK2, ERN1, BCL2, TMEM49, SMCR8

Loperamide

hsa04144

Endocytosis

8.99E-03

P11142, Q9H444, O43633, O75351, Q9NZZ3, Q15438, Q14161, P14784, Q96QK1, Q9UMY4, Q9Y5X3, Q9UNH7

HSPA8, CHMP4B, CHMP2A, VPS4B, CHMP5, PSCD1, GIT2, IL2RB, VPS35, SNX12, SNX5, SNX6

Loperamide

hsa04145

Phagosome

3.63E-04

P60709, P63261, Q15075, Q15080, P14598, Q13509, P68371, Q13488, O60603, P27824

ACTB, ACTG1, EEA1, NCF4, NCF1, TUBB3, TUBB2C, TCIRG1, TLR2, CANX

Loperamide

hsa04146

Peroxisome

2.42E-02

O43933, P56589, Q9UKG9, O75521, P33121

PEX1, PEX3, CROT, ECI2, ACSL1

Loperamide

hsa04151

PI3K-Akt signaling pathway

4.68E-03

O43521, P27348, P20827, P49767, Q13362, P08238, P62873, P16144, P48551, P14784, P23458, P01568, P15336, P18848, P10415, P17252, Q16513, Q6ZUJ8

BCL2L11, YWHAQ, EFNA1, VEGFC, PPP2R5C, HSP90AB1, GNB1, ITGB4, IFNAR2, IL2RB, JAK1, IFNA21, ATF2, ATF4, BCL2, PRKCA, PKN2, PIK3AP1

Loperamide

hsa04210

Apoptosis

7.52E-04

O76075, P07384, P01375, Q9NR28, Q16548, P60709, P63261

DFFB, CAPN1, TNF, DIABLO, BCL2A1, ACTB, ACTG1

Loperamide

hsa04213

Longevity regulating pathway - multiple species

4.41E-03

P42338, Q9Y4H2, P11142, Q13547

PIK3CB, IRS2, HSPA8, HDAC1

Loperamide

hsa04215

Apoptosis - multiple species

1.56E-02

Q13489, P10415

BIRC3, BCL2

Loperamide

hsa04217

Necroptosis

2.92E-09

P01375, P01568, P23458, P48023, Q13489, Q9NQC7, P42224, Q14765, P08238, P01584, P0C0S5, Q6FI13, Q99878, P10415, Q13557, Q9H444, O43633, Q9NZZ3, O75351

TNF, IFNA21, JAK1, FASLG, BIRC3, CYLD, STAT1, STAT4, HSP90AB1, IL1B, H2AFZ, H2AC18; H2AC19, H2AC14, BCL2, CAMK2D, CHMP4B, CHMP2A, CHMP5, VPS4B

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P14416	DRD2	D(2) dopamine receptor	P01375	TNF	Tumor necrosis factor	-0.767
P0DP23	CALM1	Calmodulin-1	P01568	IFNA21	Interferon alpha-21	-0.852
P0DP25	CALM3	Calmodulin-3	P01568	IFNA21	Interferon alpha-21	-0.852
P0DP24	CALM2	Calmodulin-2	P01568	IFNA21	Interferon alpha-21	-0.852
P0DP23	CALM1	Calmodulin-1	P23458	JAK1	Tyrosine-protein kinase JAK1	0.822
P0DP24	CALM2	Calmodulin-2	P23458	JAK1	Tyrosine-protein kinase JAK1	0.738
P14416	DRD2	D(2) dopamine receptor	P48023	FASLG	Tumor necrosis factor ligand superfamily member 6	0.7
P0DP23	CALM1	Calmodulin-1	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P0DP25	CALM3	Calmodulin-3	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P0DP24	CALM2	Calmodulin-2	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P0DP23	CALM1	Calmodulin-1	Q9NQC7	CYLD	Ubiquitin carboxyl-terminal hydrolase CYLD	0.883
P0DP24	CALM2	Calmodulin-2	Q9NQC7	CYLD	Ubiquitin carboxyl-terminal hydrolase CYLD	0.778
P0DP23	CALM1	Calmodulin-1	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP25	CALM3	Calmodulin-3	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP24	CALM2	Calmodulin-2	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P14416	DRD2	D(2) dopamine receptor	Q14765	STAT4	Signal transducer and activator of transcription 4	0.71
P0DP23	CALM1	Calmodulin-1	P08238	HSP90AB1	Heat shock protein HSP 90-beta	0.775
P0DP25	CALM3	Calmodulin-3	P08238	HSP90AB1	Heat shock protein HSP 90-beta	0.775
P0DP24	CALM2	Calmodulin-2	P08238	HSP90AB1	Heat shock protein HSP 90-beta	0.775
P0DP24	CALM2	Calmodulin-2	P01584	IL1B	Interleukin-1 beta	0.72
P0DP24	CALM2	Calmodulin-2	P0C0S5	H2AFZ	Histone H2A.Z	0.749
P0DP23	CALM1	Calmodulin-1	Q6FI13	H2AC18; H2AC19	Histone H2A type 2-A	0.81
P0DP25	CALM3	Calmodulin-3	Q6FI13	H2AC18; H2AC19	Histone H2A type 2-A	0.81
P0DP24	CALM2	Calmodulin-2	Q6FI13	H2AC18; H2AC19	Histone H2A type 2-A	0.81
P14416	DRD2	D(2) dopamine receptor	Q99878	H2AC14	Histone H2A type 1-J	-0.784
P0DP23	CALM1	Calmodulin-1	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP25	CALM3	Calmodulin-3	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP24	CALM2	Calmodulin-2	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP24	CALM2	Calmodulin-2	Q13557	CAMK2D	Calcium/calmodulin-dependent protein kinase type II subunit delta	0.786
P0DP23	CALM1	Calmodulin-1	Q9H444	CHMP4B	Charged multivesicular body protein 4b	0.73
P0DP24	CALM2	Calmodulin-2	Q9H444	CHMP4B	Charged multivesicular body protein 4b	0.713
P0DP23	CALM1	Calmodulin-1	O43633	CHMP2A	Charged multivesicular body protein 2a	0.842
P0DP25	CALM3	Calmodulin-3	O43633	CHMP2A	Charged multivesicular body protein 2a	0.842
P0DP24	CALM2	Calmodulin-2	O43633	CHMP2A	Charged multivesicular body protein 2a	0.842
P0DP23	CALM1	Calmodulin-1	Q9NZZ3	CHMP5	Charged multivesicular body protein 5	0.713
P0DP24	CALM2	Calmodulin-2	Q9NZZ3	CHMP5	Charged multivesicular body protein 5	0.763
P0DP23	CALM1	Calmodulin-1	O75351	VPS4B	Vacuolar protein sorting-associated protein 4B	0.784

Loperamide

hsa04260

Cardiac muscle contraction

4.02E-02

P09493, P14927

TPM1, UQCRB

Loperamide

hsa04261

Adrenergic signaling in cardiomyocytes

5.10E-07

P09493, Q08828, P51828, P31751, P18848, Q13362, Q16537, P0DP23, Q13557, P17252, P10415, P20020, P23634

TPM1, ADCY1, ADCY7, AKT2, ATF4, PPP2R5C, PPP2R5E, CALM1, CAMK2D, PRKCA, BCL2, ATP2B1, ATP2B4

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P0DP23	CALM1	Calmodulin-1	P09493	TPM1	Tropomyosin alpha-1 chain	-0.749
P0DP25	CALM3	Calmodulin-3	P09493	TPM1	Tropomyosin alpha-1 chain	-0.749
P0DP24	CALM2	Calmodulin-2	P09493	TPM1	Tropomyosin alpha-1 chain	-0.749
P0DP23	CALM1	Calmodulin-1	Q08828	ADCY1	Adenylate cyclase type 1	0.725
P0DP24	CALM2	Calmodulin-2	Q08828	ADCY1	Adenylate cyclase type 1	0.711
P0DP23	CALM1	Calmodulin-1	P51828	ADCY7	Adenylate cyclase type 7	0.719
P0DP23	CALM1	Calmodulin-1	P31751	AKT2	RAC-beta serine/threonine-protein kinase	0.761
P0DP24	CALM2	Calmodulin-2	P18848	ATF4	Cyclic AMP-dependent transcription factor ATF-4	0.708
P0DP23	CALM1	Calmodulin-1	Q13362	PPP2R5C	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform	0.736
P0DP24	CALM2	Calmodulin-2	Q13362	PPP2R5C	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform	0.765
P51684	CCR6	C-C chemokine receptor type 6	Q16537	PPP2R5E	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform	0.819
P0DP23	CALM1	Calmodulin-1	P0DP23	CALM1	Calmodulin-1	1
P51684	CCR6	C-C chemokine receptor type 6	P0DP23	CALM1	Calmodulin-1	-0.734
P0DP25	CALM3	Calmodulin-3	P0DP23	CALM1	Calmodulin-1	1
P0DP24	CALM2	Calmodulin-2	P0DP23	CALM1	Calmodulin-1	1
P0DP24	CALM2	Calmodulin-2	Q13557	CAMK2D	Calcium/calmodulin-dependent protein kinase type II subunit delta	0.786
P0DP23	CALM1	Calmodulin-1	P17252	PRKCA	Protein kinase C alpha type	-0.776
P51684	CCR6	C-C chemokine receptor type 6	P17252	PRKCA	Protein kinase C alpha type	0.738
P0DP25	CALM3	Calmodulin-3	P17252	PRKCA	Protein kinase C alpha type	-0.776
P0DP24	CALM2	Calmodulin-2	P17252	PRKCA	Protein kinase C alpha type	-0.776
P0DP23	CALM1	Calmodulin-1	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P51684	CCR6	C-C chemokine receptor type 6	P10415	BCL2	Apoptosis regulator Bcl-2	0.84
P0DP25	CALM3	Calmodulin-3	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP24	CALM2	Calmodulin-2	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P51684	CCR6	C-C chemokine receptor type 6	P20020	ATP2B1	Plasma membrane calcium-transporting ATPase 1	0.727
P0DP23	CALM1	Calmodulin-1	P23634	ATP2B4	Plasma membrane calcium-transporting ATPase 4	0.793
P0DP25	CALM3	Calmodulin-3	P23634	ATP2B4	Plasma membrane calcium-transporting ATPase 4	0.793
P0DP24	CALM2	Calmodulin-2	P23634	ATP2B4	Plasma membrane calcium-transporting ATPase 4	0.793

Loperamide

hsa04340

Hedgehog signaling pathway

3.32E-02

P49841, P22694

GSK3B, PRKACB

Loperamide

hsa04350

TGF-beta signaling pathway

4.88E-02

P37173

TGFBR2

Loperamide

hsa04360

Axon guidance

8.44E-04

P61073, P16333, P20827, O95631, P17252, Q13557, P23528, P19174

CXCR4, NCK1, EFNA1, NTN1, PRKCA, CAMK2D, CFL1, PLCG1

Loperamide

hsa04371

Apelin signaling pathway

3.08E-02

P62873, P31751, Q08828, P51828, Q13370, Q13485, P0DP23

GNB1, AKT2, ADCY1, ADCY7, PDE3B, SMAD4, CALM1

Loperamide

hsa04380

Osteoclast differentiation

4.18E-02

Q9NQC7, Q9UQC2, P23458, P42224, P01584, Q15080, P14598

CYLD, GAB2, JAK1, STAT1, IL1B, NCF4, NCF1

Loperamide

hsa04390

Hippo signaling pathway

8.78E-05

P60709, P63261, P84022, Q13485, Q9UJU2, O43623, Q13489

ACTB, ACTG1, SMAD3, SMAD4, LEF1, SNAI2, BIRC3

Loperamide

hsa04510

Focal adhesion

3.70E-03

P16144, O75369, Q15942, P17252, Q13489, P10415, P49767, P63261

ITGB4, FLNB, ZYX, PRKCA, BIRC3, BCL2, VEGFC, ACTG1

Loperamide

hsa04520

Adherens junction

1.85E-03

Q13485, Q9UJU2, O43623, P60709, P63261

SMAD4, LEF1, SNAI2, ACTB, ACTG1

Loperamide

hsa04530

Tight junction

6.83E-04

P60709, P63261, P16989, P56750, Q14247, P60660

ACTB, ACTG1, CSDA, CLDN17, CTTN, MYL6

Loperamide

hsa04540

Gap junction

5.21E-03

P17252, Q13509, P68371, Q08828, P51828

PRKCA, TUBB3, TUBB2C, ADCY1, ADCY7

Loperamide

hsa04610

Complement and coagulation cascades

6.30E-07

P00734, P0C0L4

F2, C4A

Loperamide

hsa04611

Platelet activation

2.61E-02

P60709, P63261

ACTB, ACTG1

Loperamide

hsa04612

Antigen processing and presentation

7.38E-04

P13765, P48382, P26715, P26717, Q13241, O43908, P01732, P01375

HLA-DOB, RFX5, KLRC1, KLRC2, KLRD1, KLRC4, CD8A, TNF

Loperamide

hsa04613

Neutrophil extracellular trap formation

2.75E-08

P17252, P11215, O60603, P05164, P08246, Q9UM07, Q13547, Q92769, P04908, Q6FI13, Q93077, P58876, P62807, P33778, Q16778, O60814, P68431, P14598, Q15080, P20160, P08311, O75015, P21730, P21462, O43315, Q16539

PRKCA, ITGAM, TLR2, MPO, ELA2, PADI4, HDAC1, HDAC2, H2AC4; H2AC8, H2AC18; H2AC19, HIST1H2AC, H2BC5, HIST1H2BC, H2BC3, HIST2H2BE, H2BC12, H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12, NCF1, NCF4, AZU1, CTSG, FCGR3B, C5AR1, FPR1, AQP9, MAPK14

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P51684	CCR6	C-C chemokine receptor type 6	P17252	PRKCA	Protein kinase C alpha type	0.738
O15245	SLC22A1	Solute carrier family 22 member 1	P11215	ITGAM	Integrin alpha-M	0.706
P22748	CA4	Carbonic anhydrase 4	O60603	TLR2	Toll-like receptor 2	0.919
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O60603	TLR2	Toll-like receptor 2	0.867
P51684	CCR6	C-C chemokine receptor type 6	O60603	TLR2	Toll-like receptor 2	-0.767
P22748	CA4	Carbonic anhydrase 4	P05164	MPO	Myeloperoxidase	0.826
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P05164	MPO	Myeloperoxidase	0.711
P22748	CA4	Carbonic anhydrase 4	P08246	ELA2	Neutrophil elastase	0.921
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P08246	ELA2	Neutrophil elastase	0.703
P51684	CCR6	C-C chemokine receptor type 6	P08246	ELA2	Neutrophil elastase	-0.706
P22748	CA4	Carbonic anhydrase 4	Q9UM07	PADI4	Protein-arginine deiminase type-4	0.856
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q9UM07	PADI4	Protein-arginine deiminase type-4	0.825
O15245	SLC22A1	Solute carrier family 22 member 1	Q13547	HDAC1	Histone deacetylase 1	-0.711
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q13547	HDAC1	Histone deacetylase 1	-0.742
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q92769	HDAC2	Histone deacetylase 2	-0.746
P51684	CCR6	C-C chemokine receptor type 6	Q92769	HDAC2	Histone deacetylase 2	0.702
P31645	SLC6A4	Sodium-dependent serotonin transporter	P04908	H2AC4; H2AC8	Histone H2A type 1-B/E	0.734
P22748	CA4	Carbonic anhydrase 4	Q6FI13	H2AC18; H2AC19	Histone H2A type 2-A	0.866
P51684	CCR6	C-C chemokine receptor type 6	Q6FI13	H2AC18; H2AC19	Histone H2A type 2-A	-0.86
P31645	SLC6A4	Sodium-dependent serotonin transporter	Q93077	HIST1H2AC	Histone H2A type 1-C	0.737
P11712	CYP2C9	Cytochrome P450 2C9	Q93077	HIST1H2AC	Histone H2A type 1-C	0.754
O15245	SLC22A1	Solute carrier family 22 member 1	P58876	H2BC5	Histone H2B type 1-D	0.947
P11712	CYP2C9	Cytochrome P450 2C9	P62807	HIST1H2BC	Histone H2B type 1-C/E/F/G/I	0.717
P51684	CCR6	C-C chemokine receptor type 6	P33778	H2BC3	Histone H2B type 1-B	0.704
P11712	CYP2C9	Cytochrome P450 2C9	P62807	HIST1H2BC	Histone H2B type 1-C/E/F/G/I	0.717
O15245	SLC22A1	Solute carrier family 22 member 1	Q16778	HIST2H2BE	Histone H2B type 2-E	0.793
O15245	SLC22A1	Solute carrier family 22 member 1	O60814	H2BC12	Histone H2B type 1-K	0.72
P11712	CYP2C9	Cytochrome P450 2C9	O60814	H2BC12	Histone H2B type 1-K	0.728
P31645	SLC6A4	Sodium-dependent serotonin transporter	P68431	H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12	Histone H3.1	0.913
P11712	CYP2C9	Cytochrome P450 2C9	P68431	H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12	Histone H3.1	0.845
P51684	CCR6	C-C chemokine receptor type 6	P14598	NCF1	Neutrophil cytosol factor 1	-0.713
P22748	CA4	Carbonic anhydrase 4	Q15080	NCF4	Neutrophil cytosol factor 4	0.951
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q15080	NCF4	Neutrophil cytosol factor 4	0.764
P51684	CCR6	C-C chemokine receptor type 6	Q15080	NCF4	Neutrophil cytosol factor 4	-0.803
P22748	CA4	Carbonic anhydrase 4	P20160	AZU1	Azurocidin	0.747
P22748	CA4	Carbonic anhydrase 4	P08311	CTSG	Cathepsin G	0.717
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P08311	CTSG	Cathepsin G	0.709
P22748	CA4	Carbonic anhydrase 4	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.81
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.893
P22748	CA4	Carbonic anhydrase 4	P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	0.826
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	1
P22748	CA4	Carbonic anhydrase 4	P21462	FPR1	fMet-Leu-Phe receptor	0.895
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P21462	FPR1	fMet-Leu-Phe receptor	0.842
P51684	CCR6	C-C chemokine receptor type 6	P21462	FPR1	fMet-Leu-Phe receptor	-0.7
P31645	SLC6A4	Sodium-dependent serotonin transporter	O43315	AQP9	Aquaporin-9	-0.764
P22748	CA4	Carbonic anhydrase 4	O43315	AQP9	Aquaporin-9	0.771
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O43315	AQP9	Aquaporin-9	0.915
P31645	SLC6A4	Sodium-dependent serotonin transporter	Q16539	MAPK14	Mitogen-activated protein kinase 14	-0.744
P22748	CA4	Carbonic anhydrase 4	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.767
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.833

Loperamide

hsa04614

Renin-angiotensin system

1.52E-02

P50052

AGTR2

Loperamide

hsa04620

Toll-like receptor signaling pathway

1.33E-02

P51617, P01568, P31751, P42224, Q8NHW4

IRAK1, IFNA21, AKT2, STAT1, CCL4L2

Loperamide

hsa04621

NOD-like receptor signaling pathway

3.16E-02

P01584, P08238, P23458, P42224, P01568, Q9H3M7, Q13489, P43490, P10415

IL1B, HSP90AB1, JAK1, STAT1, IFNA21, TXNIP, BIRC3, PBEF1, BCL2

Loperamide

hsa04623

Cytosolic DNA-sensing pathway

4.25E-02

P01568, Q8NHW4

IFNA21, CCL4L2

Loperamide

hsa04625

C-type lectin receptor signaling pathway

4.80E-02

Q9ULY5, P20749, Q14643, P01375, Q13191, Q16539

CLEC4E, BCL3, ITPR1, TNF, CBLB, MAPK14

Loperamide

hsa04630

JAK-STAT signaling pathway

1.16E-02

P31751, P10415, P42224, P23458, P14784, P16871, Q13651, P01568

AKT2, BCL2, STAT1, JAK1, IL2RB, IL7R, IL10RA, IFNA21

Loperamide

hsa04640

Hematopoietic cell lineage

5.48E-05

P13612, P08514, P21926, P14778, P27930, P11215, P15144, P11836, P25063, P07766, P09693, P01732, P09564, P13765, P01375

ITGA4, ITGA2B, CD9, IL1R1, IL1R2, ITGAM, ANPEP, MS4A1, CD24, CD3E, CD3G, CD8A, CD7, HLA-DOB, TNF

Loperamide

hsa04650

Natural killer cell mediated cytotoxicity

6.36E-08

P19174, P01375, P78314, P06239, O60880, P20963, P42338, Q13241, P26718, O14931, O75015, P26717, P26715

PLCG1, TNF, SH3BP2, LCK, SH2D1A, CD247, PIK3CB, KLRD1, KLRK1, NCR3, FCGR3B, KLRC2, KLRC1

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774
P25024	CXCR1	C-X-C chemokine receptor type 1	P01375	TNF	Tumor necrosis factor	0.718
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P78314	SH3BP2	SH3 domain-binding protein 2	0.809
P25025	CXCR2	C-X-C chemokine receptor type 2	P78314	SH3BP2	SH3 domain-binding protein 2	0.748
Q13547	HDAC1	Histone deacetylase 1	P06239	LCK	Tyrosine-protein kinase Lck	0.811
P25024	CXCR1	C-X-C chemokine receptor type 1	P06239	LCK	Tyrosine-protein kinase Lck	-0.779
Q13547	HDAC1	Histone deacetylase 1	O60880	SH2D1A	SH2 domain-containing protein 1A	0.786
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O60880	SH2D1A	SH2 domain-containing protein 1A	-0.81
P25025	CXCR2	C-X-C chemokine receptor type 2	O60880	SH2D1A	SH2 domain-containing protein 1A	-0.751
P25024	CXCR1	C-X-C chemokine receptor type 1	O60880	SH2D1A	SH2 domain-containing protein 1A	-0.788
Q13547	HDAC1	Histone deacetylase 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.87
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.77
P25025	CXCR2	C-X-C chemokine receptor type 2	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.722
P25024	CXCR1	C-X-C chemokine receptor type 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.771
Q13547	HDAC1	Histone deacetylase 1	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.774
Q13547	HDAC1	Histone deacetylase 1	Q13241	KLRD1	Natural killer cells antigen CD94	0.807
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q13241	KLRD1	Natural killer cells antigen CD94	-0.856
P25025	CXCR2	C-X-C chemokine receptor type 2	Q13241	KLRD1	Natural killer cells antigen CD94	-0.715
P25024	CXCR1	C-X-C chemokine receptor type 1	Q13241	KLRD1	Natural killer cells antigen CD94	-0.701
Q13547	HDAC1	Histone deacetylase 1	P26718	KLRK1	NKG2-D type II integral membrane protein	0.772
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P26718	KLRK1	NKG2-D type II integral membrane protein	-0.879
P25025	CXCR2	C-X-C chemokine receptor type 2	P26718	KLRK1	NKG2-D type II integral membrane protein	-0.842
P25024	CXCR1	C-X-C chemokine receptor type 1	P26718	KLRK1	NKG2-D type II integral membrane protein	-0.81
Q13547	HDAC1	Histone deacetylase 1	O14931	NCR3	Natural cytotoxicity triggering receptor 3	0.735
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.893
P25025	CXCR2	C-X-C chemokine receptor type 2	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.913
P25024	CXCR1	C-X-C chemokine receptor type 1	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.896
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P26717	KLRC2	NKG2-C type II integral membrane protein	-0.838
P25025	CXCR2	C-X-C chemokine receptor type 2	P26717	KLRC2	NKG2-C type II integral membrane protein	-0.714
P25024	CXCR1	C-X-C chemokine receptor type 1	P26717	KLRC2	NKG2-C type II integral membrane protein	-0.721
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	-0.838
P25025	CXCR2	C-X-C chemokine receptor type 2	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	-0.714
P25024	CXCR1	C-X-C chemokine receptor type 1	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	-0.721

Loperamide

hsa04657

IL-17 signaling pathway

6.19E-04

O00463, Q16539, P49841, P09341, P14780, Q9UJX4, P80188, P01375

TRAF5, MAPK14, GSK3B, CXCL1, MMP9, ANAPC5, LCN2, TNF

Loperamide

hsa04658

Th1 and Th2 cell differentiation

8.90E-06

Q04759, P07766, P20963, P09693, Q16539, P19174, P06239, Q14765, P23771, Q9UL17, P14784, P13765, Q13761

PRKCQ, CD3E, CD247, CD3G, MAPK14, PLCG1, LCK, STAT4, GATA3, TBX21, IL2RB, HLA-DOB, RUNX3

Loperamide

hsa04659

Th17 cell differentiation

3.31E-05

P25963, Q04759, Q16539, P19174, P06239, P14784, P13765, P14778, Q9UL17, P23771, P84022, Q13485, P07766, P09693, P20963

NFKBIA, PRKCQ, MAPK14, PLCG1, LCK, IL2RB, HLA-DOB, IL1R1, TBX21, GATA3, SMAD3, SMAD4, CD3E, CD3G, CD247

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	P25963	NFKBIA	NF-kappa-B inhibitor alpha	-0.728
Q13547	HDAC1	Histone deacetylase 1	Q04759	PRKCQ	Protein kinase C theta type	0.723
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q04759	PRKCQ	Protein kinase C theta type	-0.762
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.833
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
Q13547	HDAC1	Histone deacetylase 1	P06239	LCK	Tyrosine-protein kinase Lck	0.811
Q13547	HDAC1	Histone deacetylase 1	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.816
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.73
Q13547	HDAC1	Histone deacetylase 1	P14778	IL1R1	Interleukin-1 receptor type 1	-0.854
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P14778	IL1R1	Interleukin-1 receptor type 1	0.762
Q13547	HDAC1	Histone deacetylase 1	Q9UL17	TBX21	T-box transcription factor TBX21	0.817
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q9UL17	TBX21	T-box transcription factor TBX21	-0.861
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.767
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	P84022	SMAD3	Mothers against decapentaplegic homolog 3	0.769
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	-0.721
Q13547	HDAC1	Histone deacetylase 1	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.802
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.815
Q13547	HDAC1	Histone deacetylase 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.87
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.77

Loperamide

hsa04660

T cell receptor signaling pathway

7.17E-07

P01375, Q04759, P42338, O95267, Q08881, P19174, P07766, P20963, P09693, P01732, Q13191, P06239, Q16539, P49841

TNF, PRKCQ, PIK3CB, RASGRP1, ITK, PLCG1, CD3E, CD247, CD3G, CD8A, CBLB, LCK, MAPK14, GSK3B

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774
P25024	CXCR1	C-X-C chemokine receptor type 1	P01375	TNF	Tumor necrosis factor	0.718
Q13547	HDAC1	Histone deacetylase 1	Q04759	PRKCQ	Protein kinase C theta type	0.723
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q04759	PRKCQ	Protein kinase C theta type	-0.762
Q13547	HDAC1	Histone deacetylase 1	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.774
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.806
P25025	CXCR2	C-X-C chemokine receptor type 2	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.716
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.812
P25025	CXCR2	C-X-C chemokine receptor type 2	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.746
P25024	CXCR1	C-X-C chemokine receptor type 1	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.736
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
Q13547	HDAC1	Histone deacetylase 1	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.802
Q13547	HDAC1	Histone deacetylase 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.87
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.77
P25025	CXCR2	C-X-C chemokine receptor type 2	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.722
P25024	CXCR1	C-X-C chemokine receptor type 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.771
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.815
P25025	CXCR2	C-X-C chemokine receptor type 2	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.77
Q13547	HDAC1	Histone deacetylase 1	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	0.816
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.816
P25025	CXCR2	C-X-C chemokine receptor type 2	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.722
Q13547	HDAC1	Histone deacetylase 1	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	0.806
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	-0.816
P25025	CXCR2	C-X-C chemokine receptor type 2	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	-0.719
P25024	CXCR1	C-X-C chemokine receptor type 1	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	-0.734
Q13547	HDAC1	Histone deacetylase 1	P06239	LCK	Tyrosine-protein kinase Lck	0.811
P25024	CXCR1	C-X-C chemokine receptor type 1	P06239	LCK	Tyrosine-protein kinase Lck	-0.779
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.833
P25025	CXCR2	C-X-C chemokine receptor type 2	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.889
P25024	CXCR1	C-X-C chemokine receptor type 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.795
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.781
P25025	CXCR2	C-X-C chemokine receptor type 2	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.861
P25024	CXCR1	C-X-C chemokine receptor type 1	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.823

Loperamide

hsa04662

B cell receptor signaling pathway

3.68E-02

P25963, P20023

NFKBIA, CR2

Loperamide

hsa04666

Fc gamma R-mediated phagocytosis

2.00E-03

P08575, P19174, P23528, P49006, P06396, Q9UQC2, P14598, P17252

PTPRC, PLCG1, CFL1, MARCKSL1, GSN, GAB2, NCF1, PRKCA

Loperamide

hsa04670

Leukocyte transendothelial migration

4.07E-02

P60709, P63261

ACTB, ACTG1

Loperamide

hsa04713

Circadian entrainment

5.61E-05

O15399, P0DP23, Q13557, P17252, P62873, Q08828, P51828

GRIN2D, CALM1, CAMK2D, PRKCA, GNB1, ADCY1, ADCY7

Loperamide

hsa04714

Thermogenesis

3.66E-05

Q16539, P15336, P60709, P63261, P33121, Q16718, O14521, P36542

MAPK14, ATF2, ACTB, ACTG1, ACSL1, NDUFA5, SDHD, ATP5C1

Loperamide

hsa04720

Long-term potentiation

3.98E-06

P17252, Q16566, Q13557, P0DP23, P18848, O15399, Q08828, Q14643

PRKCA, CAMK4, CAMK2D, CALM1, ATF4, GRIN2D, ADCY1, ITPR1

Loperamide

hsa04722

Neurotrophin signaling pathway

3.27E-02

P49841, O43524, P48023

GSK3B, FOXO3, FASLG

Loperamide

hsa04724

Glutamatergic synapse

5.91E-03

P48058, O15399, Q08828, P51828, P17252, P62873, P15104

GRIA4, GRIN2D, ADCY1, ADCY7, PRKCA, GNB1, GLUL

Loperamide

hsa04725

Cholinergic synapse

4.42E-04

Q08828, P51828, P17252, P62873, P18848, Q13557, P31751, P10415

ADCY1, ADCY7, PRKCA, GNB1, ATF4, CAMK2D, AKT2, BCL2

Loperamide

hsa04727

GABAergic synapse

4.08E-02

Q08828, P51828, P62873, P46459, P17252

ADCY1, ADCY7, GNB1, NSF, PRKCA

Loperamide

hsa04728

Dopaminergic synapse

2.82E-02

P14416, P63218, P50151, P49841, Q16539, P49407

DRD2, GNG5, GNG10, GSK3B, MAPK14, ARRB1

Loperamide

hsa04740

Olfactory transduction

2.61E-02

P62873, Q13557, P0DP23

GNB1, CAMK2D, CALM1

Loperamide

hsa04744

Phototransduction

1.30E-05

P62873, P0DP23

GNB1, CALM1

Loperamide

hsa04750

Inflammatory mediator regulation of TRP channels

1.34E-06

P14778, P01584, Q08828, P51828, Q13557, P19174, P42338, P17252, P24723, Q04759, P0DP23, P01042

IL1R1, IL1B, ADCY1, ADCY7, CAMK2D, PLCG1, PIK3CB, PRKCA, PRKCH, PRKCQ, CALM1, KNG1

Loperamide

hsa04910

Insulin signaling pathway

2.35E-02

P22694, P06737, P49841

PRKACB, PYGL, GSK3B

Loperamide

hsa04911

Insulin secretion

3.47E-02

Q08828, P17252, P18848, Q13557

ADCY1, PRKCA, ATF4, CAMK2D

Loperamide

hsa04912

GnRH signaling pathway

5.72E-04

P17252, Q08828, P18848, Q13557, Q16539, Q9Y6R4, Q14643, P0DP23, P22694

PRKCA, ADCY1, ATF4, CAMK2D, MAPK14, MAP3K4, ITPR1, CALM1, PRKACB

Loperamide

hsa04914

Progesterone-mediated oocyte maturation

3.26E-02

Q08828, P51828, P31751, Q13370, Q9UJX4, P08238

ADCY1, ADCY7, AKT2, PDE3B, ANAPC5, HSP90AB1

Loperamide

hsa04915

Estrogen signaling pathway

3.28E-03

P18848, Q08828, P51828, P31751, P08238, P11142, P0DP23, Q15788, P10415

ATF4, ADCY1, ADCY7, AKT2, HSP90AB1, HSPA8, CALM1, NCOA1, BCL2

Loperamide

hsa04916

Melanogenesis

3.55E-02

P0DP23, Q9UJU2, P17252

CALM1, LEF1, PRKCA

Loperamide

hsa04919

Thyroid hormone signaling pathway

5.60E-04

P49841, P22694, P60709, P63261, O60244, Q9NVC6

GSK3B, PRKACB, ACTB, ACTG1, MED14, MED17

Loperamide

hsa04920

Adipocytokine signaling pathway

4.72E-02

P33121, Q04759, Q9Y4H2, P01375

ACSL1, PRKCQ, IRS2, TNF

Loperamide

hsa04921

Oxytocin signaling pathway

9.08E-04

P0DP23, P17252, Q16566, P60660, P60709, P63261

CALM1, PRKCA, CAMK4, MYL6, ACTB, ACTG1

Loperamide

hsa04923

Regulation of lipolysis in adipocytes

1.20E-03

Q08828, P51828, P07550, Q13370, P42338, Q9Y4H2, P31751

ADCY1, ADCY7, ADRB2, PDE3B, PIK3CB, IRS2, AKT2

Loperamide

hsa04925

Aldosterone synthesis and secretion

9.45E-07

Q14643, P18848, Q08828, P51828, P0DP23, P17252, Q16566, Q13557, P20020, P23634

ITPR1, ATF4, ADCY1, ADCY7, CALM1, PRKCA, CAMK4, CAMK2D, ATP2B1, ATP2B4

Loperamide

hsa04931

Insulin resistance

1.94E-02

P01375, P49841, P06737

TNF, GSK3B, PYGL

Loperamide

hsa04932

Non-alcoholic fatty liver disease

2.44E-03

P01375, P49841, P48023, Q16718, O14521

TNF, GSK3B, FASLG, NDUFA5, SDHD

Loperamide

hsa04933

AGE-RAGE signaling pathway in diabetic complications

1.63E-08

P84022, Q13485, P01584, P42224, P10415, P31751, P49767, P17252, P19174

SMAD3, SMAD4, IL1B, STAT1, BCL2, AKT2, VEGFC, PRKCA, PLCG1

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	P84022	SMAD3	Mothers against decapentaplegic homolog 3	0.769
P0DP23	CALM1	Calmodulin-1	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	0.777
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	-0.721
P46091	GPR1	Chemerin-like receptor 2	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	-0.809
P0DP25	CALM3	Calmodulin-3	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	0.777
P0DP24	CALM2	Calmodulin-2	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	0.777
P0DP24	CALM2	Calmodulin-2	P01584	IL1B	Interleukin-1 beta	0.72
P0DP23	CALM1	Calmodulin-1	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP25	CALM3	Calmodulin-3	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP24	CALM2	Calmodulin-2	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP23	CALM1	Calmodulin-1	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	P10415	BCL2	Apoptosis regulator Bcl-2	0.742
P46091	GPR1	Chemerin-like receptor 2	P10415	BCL2	Apoptosis regulator Bcl-2	0.808
P0DP25	CALM3	Calmodulin-3	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP24	CALM2	Calmodulin-2	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP23	CALM1	Calmodulin-1	P31751	AKT2	RAC-beta serine/threonine-protein kinase	0.761
P0DP23	CALM1	Calmodulin-1	P49767	VEGFC	Vascular endothelial growth factor C	-0.84
P46091	GPR1	Chemerin-like receptor 2	P49767	VEGFC	Vascular endothelial growth factor C	0.718
P0DP25	CALM3	Calmodulin-3	P49767	VEGFC	Vascular endothelial growth factor C	-0.84
P0DP24	CALM2	Calmodulin-2	P49767	VEGFC	Vascular endothelial growth factor C	-0.84
P0DP23	CALM1	Calmodulin-1	P17252	PRKCA	Protein kinase C alpha type	-0.776
P46091	GPR1	Chemerin-like receptor 2	P17252	PRKCA	Protein kinase C alpha type	0.741
P0DP25	CALM3	Calmodulin-3	P17252	PRKCA	Protein kinase C alpha type	-0.776
P0DP24	CALM2	Calmodulin-2	P17252	PRKCA	Protein kinase C alpha type	-0.776
P0DP23	CALM1	Calmodulin-1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
P0DP25	CALM3	Calmodulin-3	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
P0DP24	CALM2	Calmodulin-2	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744

Loperamide

hsa04935

Growth hormone synthesis, secretion and action

3.93E-02

P19174, Q08828, P51828, P17252, P31751, P42224

PLCG1, ADCY1, ADCY7, PRKCA, AKT2, STAT1

Loperamide

hsa04940

Type I diabetes mellitus

1.87E-02

P48023, P01375

FASLG, TNF

Loperamide

hsa04964

Proximal tubule bicarbonate reclamation

4.93E-02

P00918

CA2

Loperamide

hsa04966

Collecting duct acid secretion

2.32E-03

P02730, P00918, Q9Y666

SLC4A1, CA2, SLC12A7

Loperamide

hsa04970

Salivary secretion

4.80E-06

Q08828, P51828, Q14643, P20020, P23634, P17252, P0DP23

ADCY1, ADCY7, ITPR1, ATP2B1, ATP2B4, PRKCA, CALM1

Loperamide

hsa04971

Gastric acid secretion

2.67E-03

P17252, P60709, P63261, P0DP23

PRKCA, ACTB, ACTG1, CALM1

Loperamide

hsa04972

Pancreatic secretion

7.98E-05

Q14643, P20020, P23634, P17252, Q08828, P51828, P62491

ITPR1, ATP2B1, ATP2B4, PRKCA, ADCY1, ADCY7, RAB11A

Loperamide

hsa04973

Carbohydrate digestion and absorption

1.29E-02

O43451, P42338

MGAM, PIK3CB

Loperamide

hsa04975

Fat digestion and absorption

3.43E-02

O14494

PLPP1

Loperamide

hsa04976

Bile secretion

1.67E-03

O43315, P22694, P08183

AQP9, PRKACB, ABCB1

Loperamide

hsa04978

Mineral absorption

3.94E-02

P23634, Q9BXS9

ATP2B4, SLC26A6

Loperamide

hsa05014

Amyotrophic lateral sclerosis

8.60E-03

O15399, P10415, P36542, Q13509, P68371, Q53GS7, P60709, P63261, Q9GZY0

GRIN2D, BCL2, ATP5C1, TUBB3, TUBB2C, GLE1, ACTB, ACTG1, NXF2; NXF2B

Loperamide

hsa05016

Huntington disease

2.46E-05

Q9GZM3, P52435, Q9NYC9

POLR2J2, POLR2J, DNAH9

Loperamide

hsa05017

Spinocerebellar ataxia

3.80E-03

P17252, O75460, Q8TB72, O15399, P31751, P28070, P43686, O00232

PRKCA, ERN1, PUM2, GRIN2D, AKT2, PSMB4, PSMC4, PSMD12

Loperamide

hsa05020

Prion disease

3.80E-02

Q16718, O14521, P49841, Q16539

NDUFA5, SDHD, GSK3B, MAPK14

Loperamide

hsa05022

Pathways of neurodegeneration - multiple diseases

1.24E-02

P49841, Q16718, O14521, Q13561, Q16539, Q08752

GSK3B, NDUFA5, SDHD, DCTN2, MAPK14, PPID

Loperamide

hsa05031

Amphetamine addiction

1.35E-03

O15399, P0DP23, Q16566, Q13557, P18848, P17252

GRIN2D, CALM1, CAMK4, CAMK2D, ATF4, PRKCA

Loperamide

hsa05032

Morphine addiction

4.08E-02

Q08828, P51828, P62873, Q13370, P17252

ADCY1, ADCY7, GNB1, PDE3B, PRKCA

Loperamide

hsa05034

Alcoholism

2.05E-05

Q13547, Q93077, P58876, P62807, Q16778, O60814, P68431

HDAC1, HIST1H2AC, H2BC5, HIST1H2BC, HIST2H2BE, H2BC12, H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12

Loperamide

hsa05100

Bacterial invasion of epithelial cells

8.79E-04

P60709, P63261, Q92529

ACTB, ACTG1, SHC3

Loperamide

hsa05110

Vibrio cholerae infection

3.95E-03

P60709, P63261

ACTB, ACTG1

Loperamide

hsa05120

Epithelial cell signaling in Helicobacter pylori infection

2.62E-04

Q16539, P09341, P19875, P19174, P25024, P25025, P07948

MAPK14, CXCL1, CXCL2, PLCG1, CXCR1, CXCR2, LYN

Loperamide

hsa05131

Shigellosis

1.91E-02

P60709, P63261, P07384

ACTB, ACTG1, CAPN1

Loperamide

hsa05132

Salmonella infection

4.75E-08

P51617, P01584, P25963, P08238, Q9UJU2, P63261, Q96RF0, Q13546, Q13489, P10415, P08575, O75369, O60603, Q9BQS8, P51808, Q13561, Q13509, P68371, P49754, Q9NP90

IRAK1, IL1B, NFKBIA, HSP90AB1, LEF1, ACTG1, SNAG1, RIPK1, BIRC3, BCL2, PTPRC, FLNB, TLR2, FYCO1, DYNLT3, DCTN2, TUBB3, TUBB2C, VPS41, RAB9B

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P51684	CCR6	C-C chemokine receptor type 6	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	0.722
P0DP25	CALM3	Calmodulin-3	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P0DP24	CALM2	Calmodulin-2	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P0DP24	CALM2	Calmodulin-2	P01584	IL1B	Interleukin-1 beta	0.72
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	P25963	NFKBIA	NF-kappa-B inhibitor alpha	-0.728
P0DP25	CALM3	Calmodulin-3	P08238	HSP90AB1	Heat shock protein HSP 90-beta	0.775
P0DP24	CALM2	Calmodulin-2	P08238	HSP90AB1	Heat shock protein HSP 90-beta	0.775
P46091	GPR1	Chemerin-like receptor 2	Q9UJU2	LEF1	Lymphoid enhancer-binding factor 1	0.736
P51684	CCR6	C-C chemokine receptor type 6	Q9UJU2	LEF1	Lymphoid enhancer-binding factor 1	0.835
P46091	GPR1	Chemerin-like receptor 2	P63261	ACTG1	Actin, cytoplasmic 2	0.776
P0DP24	CALM2	Calmodulin-2	Q96RF0	SNAG1	Sorting nexin-18	0.703
P51684	CCR6	C-C chemokine receptor type 6	Q13546	RIPK1	Receptor-interacting serine/threonine-protein kinase 1	-0.868
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	0.708
P46091	GPR1	Chemerin-like receptor 2	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	0.759
P0DP25	CALM3	Calmodulin-3	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P0DP24	CALM2	Calmodulin-2	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	P10415	BCL2	Apoptosis regulator Bcl-2	0.742
P46091	GPR1	Chemerin-like receptor 2	P10415	BCL2	Apoptosis regulator Bcl-2	0.808
P51684	CCR6	C-C chemokine receptor type 6	P10415	BCL2	Apoptosis regulator Bcl-2	0.84
P0DP25	CALM3	Calmodulin-3	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP24	CALM2	Calmodulin-2	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP24	CALM2	Calmodulin-2	P08575	PTPRC	Receptor-type tyrosine-protein phosphatase C	0.716
P51684	CCR6	C-C chemokine receptor type 6	O75369	FLNB	Filamin-B	-0.717
P0DP25	CALM3	Calmodulin-3	O75369	FLNB	Filamin-B	0.874
P0DP24	CALM2	Calmodulin-2	O75369	FLNB	Filamin-B	0.874
P51684	CCR6	C-C chemokine receptor type 6	O60603	TLR2	Toll-like receptor 2	-0.767
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	Q9BQS8	FYCO1	FYVE and coiled-coil domain-containing protein 1	0.722
P51684	CCR6	C-C chemokine receptor type 6	Q9BQS8	FYCO1	FYVE and coiled-coil domain-containing protein 1	0.721
P51684	CCR6	C-C chemokine receptor type 6	P51808	DYNLT3	Dynein light chain Tctex-type 3	0.731
P51684	CCR6	C-C chemokine receptor type 6	Q13561	DCTN2	Dynactin subunit 2	-0.781
P0DP25	CALM3	Calmodulin-3	Q13561	DCTN2	Dynactin subunit 2	0.739
P0DP24	CALM2	Calmodulin-2	Q13561	DCTN2	Dynactin subunit 2	0.739
P46091	GPR1	Chemerin-like receptor 2	Q13509	TUBB3	Tubulin beta-3 chain	-0.748
P51684	CCR6	C-C chemokine receptor type 6	Q13509	TUBB3	Tubulin beta-3 chain	-0.835
P0DP25	CALM3	Calmodulin-3	Q13509	TUBB3	Tubulin beta-3 chain	0.892
P0DP24	CALM2	Calmodulin-2	Q13509	TUBB3	Tubulin beta-3 chain	0.892
P46091	GPR1	Chemerin-like receptor 2	P68371	TUBB2C	Tubulin beta-4B chain	-0.751
P0DP25	CALM3	Calmodulin-3	P68371	TUBB2C	Tubulin beta-4B chain	0.742
P0DP24	CALM2	Calmodulin-2	P68371	TUBB2C	Tubulin beta-4B chain	0.742
P0DP25	CALM3	Calmodulin-3	P49754	VPS41	Vacuolar protein sorting-associated protein 41 homolog	0.723
P0DP24	CALM2	Calmodulin-2	P49754	VPS41	Vacuolar protein sorting-associated protein 41 homolog	0.723
P0DP24	CALM2	Calmodulin-2	Q9NP90	RAB9B	Ras-related protein Rab-9B	0.791

Loperamide

hsa05133

Pertussis

2.88E-07

P0DP23, P01584, P23528, P09871, P0C0L4, P51617

CALM1, IL1B, CFL1, C1S, C4A, IRAK1

Loperamide

hsa05134

Legionellosis

1.29E-02

P11215, P11142, P09341, P19875

ITGAM, HSPA8, CXCL1, CXCL2

Loperamide

hsa05135

Yersinia infection

5.31E-03

P60709, P63261, Q16513, P13612, P06239, Q16539, P01375, P49841

ACTB, ACTG1, PKN2, ITGA4, LCK, MAPK14, TNF, GSK3B

Loperamide

hsa05140

Leishmaniasis

5.06E-05

P13612, O75015, P14598, P13765, O60603, P25963, P01375, P29350, P49006, Q16539, P51617, Q15080

ITGA4, FCGR3B, NCF1, HLA-DOB, TLR2, NFKBIA, TNF, PTPN6, MARCKSL1, MAPK14, IRAK1, NCF4

Loperamide

hsa05143

African trypanosomiasis

2.13E-05

P01375, P01584, P69905, P68871, P48023, P17252, P01042

TNF, IL1B, HBA2, HBB, FASLG, PRKCA, KNG1

Loperamide

hsa05144

Malaria

1.12E-05

P60033, P69905, P68871, O60603, P01375, P35443, P26718

CD81, HBA2, HBB, TLR2, TNF, THBS4, KLRK1

Loperamide

hsa05145

Toxoplasmosis

7.31E-06

P51617, P25963, P10415, Q13489, P23458, P42224, P31751, P11142, P29965, Q13651

IRAK1, NFKBIA, BCL2, BIRC3, JAK1, STAT1, AKT2, HSPA8, CD40LG, IL10RA

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P0DP23	CALM1	Calmodulin-1	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P0DP25	CALM3	Calmodulin-3	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P0DP24	CALM2	Calmodulin-2	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	P25963	NFKBIA	NF-kappa-B inhibitor alpha	-0.728
P0DP23	CALM1	Calmodulin-1	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	P10415	BCL2	Apoptosis regulator Bcl-2	0.742
P0DP25	CALM3	Calmodulin-3	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP24	CALM2	Calmodulin-2	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP23	CALM1	Calmodulin-1	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	0.708
P0DP25	CALM3	Calmodulin-3	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P0DP24	CALM2	Calmodulin-2	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P0DP23	CALM1	Calmodulin-1	P23458	JAK1	Tyrosine-protein kinase JAK1	0.822
P0DP24	CALM2	Calmodulin-2	P23458	JAK1	Tyrosine-protein kinase JAK1	0.738
P0DP23	CALM1	Calmodulin-1	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP25	CALM3	Calmodulin-3	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP24	CALM2	Calmodulin-2	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP23	CALM1	Calmodulin-1	P31751	AKT2	RAC-beta serine/threonine-protein kinase	0.761
P0DP23	CALM1	Calmodulin-1	P11142	HSPA8	Heat shock cognate 71 kDa protein	0.804
P0DP25	CALM3	Calmodulin-3	P11142	HSPA8	Heat shock cognate 71 kDa protein	0.804
P0DP24	CALM2	Calmodulin-2	P11142	HSPA8	Heat shock cognate 71 kDa protein	0.804
P0DP23	CALM1	Calmodulin-1	P29965	CD40LG	CD40 ligand	-0.721
P0DP25	CALM3	Calmodulin-3	P29965	CD40LG	CD40 ligand	-0.721
P0DP24	CALM2	Calmodulin-2	P29965	CD40LG	CD40 ligand	-0.721
P0DP23	CALM1	Calmodulin-1	Q13651	IL10RA	Interleukin-10 receptor subunit alpha	0.701

Loperamide

hsa05146

Amoebiasis

8.90E-06

P09341, P19875, P14778, P27930, P01375, O60603, P42338, P11215, P05089, P22694, P12814, P08311

CXCL1, CXCL2, IL1R1, IL1R2, TNF, TLR2, PIK3CB, ITGAM, ARG1, PRKACB, ACTN1, CTSG

Loperamide

hsa05160

Hepatitis C

1.27E-02

P60033, P49841, P01375, P48023

CD81, GSK3B, TNF, FASLG

Loperamide

hsa05161

Hepatitis B

1.11E-05

P17252, P18848, P23458, P25963, Q13485, P31751, P10415, P27348, P84022, P01568, P42224, P51617

PRKCA, ATF4, JAK1, NFKBIA, SMAD4, AKT2, BCL2, YWHAQ, SMAD3, IFNA21, STAT1, IRAK1

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P0DP23	CALM1	Calmodulin-1	P17252	PRKCA	Protein kinase C alpha type	-0.776
P0DP25	CALM3	Calmodulin-3	P17252	PRKCA	Protein kinase C alpha type	-0.776
P0DP24	CALM2	Calmodulin-2	P17252	PRKCA	Protein kinase C alpha type	-0.776
P0DP24	CALM2	Calmodulin-2	P18848	ATF4	Cyclic AMP-dependent transcription factor ATF-4	0.708
P0DP23	CALM1	Calmodulin-1	P23458	JAK1	Tyrosine-protein kinase JAK1	0.822
P0DP24	CALM2	Calmodulin-2	P23458	JAK1	Tyrosine-protein kinase JAK1	0.738
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	P25963	NFKBIA	NF-kappa-B inhibitor alpha	-0.728
P0DP23	CALM1	Calmodulin-1	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	0.777
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	-0.721
P0DP25	CALM3	Calmodulin-3	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	0.777
P0DP24	CALM2	Calmodulin-2	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	0.777
P0DP23	CALM1	Calmodulin-1	P31751	AKT2	RAC-beta serine/threonine-protein kinase	0.761
P0DP23	CALM1	Calmodulin-1	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	P10415	BCL2	Apoptosis regulator Bcl-2	0.742
P0DP25	CALM3	Calmodulin-3	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP24	CALM2	Calmodulin-2	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP24	CALM2	Calmodulin-2	P27348	YWHAQ	14-3-3 protein theta	0.777
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	P84022	SMAD3	Mothers against decapentaplegic homolog 3	0.769
P0DP23	CALM1	Calmodulin-1	P01568	IFNA21	Interferon alpha-21	-0.852
P0DP25	CALM3	Calmodulin-3	P01568	IFNA21	Interferon alpha-21	-0.852
P0DP24	CALM2	Calmodulin-2	P01568	IFNA21	Interferon alpha-21	-0.852
P0DP23	CALM1	Calmodulin-1	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP25	CALM3	Calmodulin-3	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP24	CALM2	Calmodulin-2	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP23	CALM1	Calmodulin-1	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P0DP25	CALM3	Calmodulin-3	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P0DP24	CALM2	Calmodulin-2	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703

Loperamide

hsa05162

Measles

1.74E-04

P51617, P01568, P23458, P42224, P14784, P31751, P11142, P01584, Q9NP90, P10415

IRAK1, IFNA21, JAK1, STAT1, IL2RB, AKT2, HSPA8, IL1B, RAB9B, BCL2

Loperamide

hsa05163

Human cytomegalovirus infection

2.07E-04

P31751, P01375, P62873, P63218, P50151, P0DP23, Q8NHW4, Q08828, P51828, P23458, P49841, P14778, P01584, P61073, P17252, Q13651, P25025, Q16539, P18848, O00463, P61769, P01568

AKT2, TNF, GNB1, GNG5, GNG10, CALM1, CCL4L2, ADCY1, ADCY7, JAK1, GSK3B, IL1R1, IL1B, CXCR4, PRKCA, IL10RA, CXCR2, MAPK14, ATF4, TRAF5, B2M, IFNA21

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P0DP23	CALM1	Calmodulin-1	P31751	AKT2	RAC-beta serine/threonine-protein kinase	0.761
P25024	CXCR1	C-X-C chemokine receptor type 1	P01375	TNF	Tumor necrosis factor	0.718
P0DP23	CALM1	Calmodulin-1	P62873	GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	0.853
P0DP24	CALM2	Calmodulin-2	P62873	GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	0.853
P25024	CXCR1	C-X-C chemokine receptor type 1	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	0.727
P25024	CXCR1	C-X-C chemokine receptor type 1	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	0.743
P0DP23	CALM1	Calmodulin-1	P0DP23	CALM1	Calmodulin-1	1
P0DP24	CALM2	Calmodulin-2	P0DP23	CALM1	Calmodulin-1	1
P0DP23	CALM1	Calmodulin-1	Q8NHW4	CCL4L2	C-C motif chemokine 4-like	0.729
P0DP23	CALM1	Calmodulin-1	Q8NHW4	CCL4L2	C-C motif chemokine 4-like	0.729
P0DP23	CALM1	Calmodulin-1	Q08828	ADCY1	Adenylate cyclase type 1	0.725
P0DP24	CALM2	Calmodulin-2	Q08828	ADCY1	Adenylate cyclase type 1	0.711
P0DP23	CALM1	Calmodulin-1	P51828	ADCY7	Adenylate cyclase type 7	0.719
P0DP23	CALM1	Calmodulin-1	P23458	JAK1	Tyrosine-protein kinase JAK1	0.822
P0DP24	CALM2	Calmodulin-2	P23458	JAK1	Tyrosine-protein kinase JAK1	0.738
P25024	CXCR1	C-X-C chemokine receptor type 1	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.823
P25024	CXCR1	C-X-C chemokine receptor type 1	P14778	IL1R1	Interleukin-1 receptor type 1	0.857
P0DP24	CALM2	Calmodulin-2	P01584	IL1B	Interleukin-1 beta	0.72
P0DP24	CALM2	Calmodulin-2	P61073	CXCR4	C-X-C chemokine receptor type 4	0.759
P0DP23	CALM1	Calmodulin-1	P17252	PRKCA	Protein kinase C alpha type	-0.776
P0DP24	CALM2	Calmodulin-2	P17252	PRKCA	Protein kinase C alpha type	-0.776
P0DP23	CALM1	Calmodulin-1	Q13651	IL10RA	Interleukin-10 receptor subunit alpha	0.701
P25024	CXCR1	C-X-C chemokine receptor type 1	P25025	CXCR2	C-X-C chemokine receptor type 2	0.929
P25024	CXCR1	C-X-C chemokine receptor type 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.795
P0DP24	CALM2	Calmodulin-2	P18848	ATF4	Cyclic AMP-dependent transcription factor ATF-4	0.708
P25024	CXCR1	C-X-C chemokine receptor type 1	O00463	TRAF5	TNF receptor-associated factor 5	-0.788
P0DP24	CALM2	Calmodulin-2	P61769	B2M	Beta-2-microglobulin	0.787
P0DP23	CALM1	Calmodulin-1	P01568	IFNA21	Interferon alpha-21	-0.852
P0DP24	CALM2	Calmodulin-2	P01568	IFNA21	Interferon alpha-21	-0.852

Loperamide

hsa05164

Influenza A

7.10E-03

P48551, P60709, P63261

IFNAR2, ACTB, ACTG1

Loperamide

hsa05168

Herpes simplex virus 1 infection

1.97E-06

Q9UKJ0, P01568, P01584, Q9UBU9, Q9GZY0, P23458, P42224, Q07955, Q01130, Q13243, Q13489, P51617, P61769, P31751, Q13398, Q6P280, Q03923, Q9UDV6, P10415, Q14232

PILRB, IFNA21, IL1B, NXF1, NXF2; NXF2B, JAK1, STAT1, SFRS1, SFRS2, SFRS5, BIRC3, IRAK1, B2M, AKT2, ZNF211, ZNF529, ZNF85, ZNF212, BCL2, EIF2B1

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P46091	GPR1	Chemerin-like receptor 2	Q9UKJ0	PILRB	Paired immunoglobulin-like type 2 receptor beta	-0.781
P0DP23	CALM1	Calmodulin-1	P01568	IFNA21	Interferon alpha-21	-0.852
P46091	GPR1	Chemerin-like receptor 2	P01568	IFNA21	Interferon alpha-21	0.724
P0DP25	CALM3	Calmodulin-3	P01568	IFNA21	Interferon alpha-21	-0.852
P0DP24	CALM2	Calmodulin-2	P01568	IFNA21	Interferon alpha-21	-0.852
P0DP24	CALM2	Calmodulin-2	P01584	IL1B	Interleukin-1 beta	0.72
P0DP23	CALM1	Calmodulin-1	Q9UBU9	NXF1	Nuclear RNA export factor 1	0.743
P0DP24	CALM2	Calmodulin-2	Q9UBU9	NXF1	Nuclear RNA export factor 1	0.772
P46091	GPR1	Chemerin-like receptor 2	Q9GZY0	NXF2; NXF2B	Nuclear RNA export factor 2	0.707
P0DP23	CALM1	Calmodulin-1	P23458	JAK1	Tyrosine-protein kinase JAK1	0.822
P0DP24	CALM2	Calmodulin-2	P23458	JAK1	Tyrosine-protein kinase JAK1	0.738
P0DP23	CALM1	Calmodulin-1	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP25	CALM3	Calmodulin-3	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP24	CALM2	Calmodulin-2	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP23	CALM1	Calmodulin-1	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	0.914
P0DP25	CALM3	Calmodulin-3	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	0.914
P0DP24	CALM2	Calmodulin-2	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	0.914
P0DP23	CALM1	Calmodulin-1	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	0.841
P46091	GPR1	Chemerin-like receptor 2	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	-0.746
P0DP25	CALM3	Calmodulin-3	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	0.841
P0DP24	CALM2	Calmodulin-2	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	0.841
P0DP23	CALM1	Calmodulin-1	Q13243	SFRS5	Serine/arginine-rich splicing factor 5	0.784
P0DP25	CALM3	Calmodulin-3	Q13243	SFRS5	Serine/arginine-rich splicing factor 5	0.784
P0DP24	CALM2	Calmodulin-2	Q13243	SFRS5	Serine/arginine-rich splicing factor 5	0.784
P0DP23	CALM1	Calmodulin-1	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P46091	GPR1	Chemerin-like receptor 2	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	0.759
P0DP25	CALM3	Calmodulin-3	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P0DP24	CALM2	Calmodulin-2	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P0DP23	CALM1	Calmodulin-1	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P0DP25	CALM3	Calmodulin-3	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P0DP24	CALM2	Calmodulin-2	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P0DP24	CALM2	Calmodulin-2	P61769	B2M	Beta-2-microglobulin	0.787
P0DP23	CALM1	Calmodulin-1	P31751	AKT2	RAC-beta serine/threonine-protein kinase	0.761
P0DP23	CALM1	Calmodulin-1	Q13398	ZNF211	Zinc finger protein 211	0.898
P46091	GPR1	Chemerin-like receptor 2	Q13398	ZNF211	Zinc finger protein 211	-0.71
P0DP25	CALM3	Calmodulin-3	Q13398	ZNF211	Zinc finger protein 211	0.898
P0DP24	CALM2	Calmodulin-2	Q13398	ZNF211	Zinc finger protein 211	0.898
P0DP23	CALM1	Calmodulin-1	Q6P280	ZNF529	Zinc finger protein 529	0.767
P0DP23	CALM1	Calmodulin-1	Q03923	ZNF85	Zinc finger protein 85	-0.818
P46091	GPR1	Chemerin-like receptor 2	Q03923	ZNF85	Zinc finger protein 85	0.705
P0DP25	CALM3	Calmodulin-3	Q03923	ZNF85	Zinc finger protein 85	-0.818
P0DP24	CALM2	Calmodulin-2	Q03923	ZNF85	Zinc finger protein 85	-0.818
P0DP23	CALM1	Calmodulin-1	Q9UDV6	ZNF212	Zinc finger protein 212	0.759
P46091	GPR1	Chemerin-like receptor 2	Q9UDV6	ZNF212	Zinc finger protein 212	-0.75
P0DP25	CALM3	Calmodulin-3	Q9UDV6	ZNF212	Zinc finger protein 212	0.759
P0DP24	CALM2	Calmodulin-2	Q9UDV6	ZNF212	Zinc finger protein 212	0.759
P0DP23	CALM1	Calmodulin-1	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P46091	GPR1	Chemerin-like receptor 2	P10415	BCL2	Apoptosis regulator Bcl-2	0.808
P0DP25	CALM3	Calmodulin-3	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP24	CALM2	Calmodulin-2	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP23	CALM1	Calmodulin-1	Q14232	EIF2B1	Translation initiation factor eIF-2B subunit alpha	0.797

Loperamide

hsa05169

Epstein-Barr virus infection

2.54E-02

Q92769, P04637, Q13546, P10415, P24522, O60603, P51617, P09693

HDAC2, TP53, RIPK1, BCL2, GADD45A, TLR2, IRAK1, CD3G

Loperamide

hsa05170

Human immunodeficiency virus 1 infection

1.16E-06

P31751, P62873, P0DP23, P61073, P17252, Q13546, P61769, Q14643, P01568, P51617, O60603, P19174, P23528, P09693, P10415, Q9Y6Q5

AKT2, GNB1, CALM1, CXCR4, PRKCA, RIPK1, B2M, ITPR1, IFNA21, IRAK1, TLR2, PLCG1, CFL1, CD3G, BCL2, AP1M2

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P0DP23	CALM1	Calmodulin-1	P31751	AKT2	RAC-beta serine/threonine-protein kinase	0.761
P0DP23	CALM1	Calmodulin-1	P62873	GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	0.853
P0DP25	CALM3	Calmodulin-3	P62873	GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	0.853
P0DP24	CALM2	Calmodulin-2	P62873	GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	0.853
P0DP23	CALM1	Calmodulin-1	P0DP23	CALM1	Calmodulin-1	1
P51684	CCR6	C-C chemokine receptor type 6	P0DP23	CALM1	Calmodulin-1	-0.734
P0DP25	CALM3	Calmodulin-3	P0DP23	CALM1	Calmodulin-1	1
P0DP24	CALM2	Calmodulin-2	P0DP23	CALM1	Calmodulin-1	1
P0DP24	CALM2	Calmodulin-2	P61073	CXCR4	C-X-C chemokine receptor type 4	0.759
P0DP23	CALM1	Calmodulin-1	P17252	PRKCA	Protein kinase C alpha type	-0.776
P51684	CCR6	C-C chemokine receptor type 6	P17252	PRKCA	Protein kinase C alpha type	0.738
P0DP25	CALM3	Calmodulin-3	P17252	PRKCA	Protein kinase C alpha type	-0.776
P0DP24	CALM2	Calmodulin-2	P17252	PRKCA	Protein kinase C alpha type	-0.776
P51684	CCR6	C-C chemokine receptor type 6	Q13546	RIPK1	Receptor-interacting serine/threonine-protein kinase 1	-0.868
P0DP24	CALM2	Calmodulin-2	P61769	B2M	Beta-2-microglobulin	0.787
P51684	CCR6	C-C chemokine receptor type 6	Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	0.81
P0DP23	CALM1	Calmodulin-1	P01568	IFNA21	Interferon alpha-21	-0.852
P0DP25	CALM3	Calmodulin-3	P01568	IFNA21	Interferon alpha-21	-0.852
P0DP24	CALM2	Calmodulin-2	P01568	IFNA21	Interferon alpha-21	-0.852
P0DP23	CALM1	Calmodulin-1	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P51684	CCR6	C-C chemokine receptor type 6	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	0.722
P0DP25	CALM3	Calmodulin-3	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P0DP24	CALM2	Calmodulin-2	P51617	IRAK1	Interleukin-1 receptor-associated kinase 1	-0.703
P51684	CCR6	C-C chemokine receptor type 6	O60603	TLR2	Toll-like receptor 2	-0.767
P0DP23	CALM1	Calmodulin-1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
P0DP25	CALM3	Calmodulin-3	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
P0DP24	CALM2	Calmodulin-2	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
P0DP23	CALM1	Calmodulin-1	P23528	CFL1	Cofilin-1	-0.832
P0DP25	CALM3	Calmodulin-3	P23528	CFL1	Cofilin-1	-0.832
P0DP24	CALM2	Calmodulin-2	P23528	CFL1	Cofilin-1	-0.832
P51684	CCR6	C-C chemokine receptor type 6	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	0.753
P0DP23	CALM1	Calmodulin-1	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P51684	CCR6	C-C chemokine receptor type 6	P10415	BCL2	Apoptosis regulator Bcl-2	0.84
P0DP25	CALM3	Calmodulin-3	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP24	CALM2	Calmodulin-2	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP23	CALM1	Calmodulin-1	Q9Y6Q5	AP1M2	AP-1 complex subunit mu-2	0.742
P51684	CCR6	C-C chemokine receptor type 6	Q9Y6Q5	AP1M2	AP-1 complex subunit mu-2	-0.86
P0DP25	CALM3	Calmodulin-3	Q9Y6Q5	AP1M2	AP-1 complex subunit mu-2	0.742
P0DP24	CALM2	Calmodulin-2	Q9Y6Q5	AP1M2	AP-1 complex subunit mu-2	0.742

Loperamide

hsa05200

Pathways in cancer

2.92E-10

P23458, P08238, P42224, P19174, Q15311, Q9UJU2, P17252, P43246, Q13485, P14923, P10415, Q13489, P49767, P31751, P25116, Q08828, P51828, P62873, P61073, P78417, O75293, Q15788, P0DP23, Q13557, O43521, P01568, P14784, P16871, P00734, P01042

JAK1, HSP90AB1, STAT1, PLCG1, RALBP1, LEF1, PRKCA, MSH2, SMAD4, JUP, BCL2, BIRC3, VEGFC, AKT2, F2R, ADCY1, ADCY7, GNB1, CXCR4, GSTO1, GADD45B, NCOA1, CALM1, CAMK2D, BCL2L11, IFNA21, IL2RB, IL7R, F2, KNG1

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P0DP23	CALM1	Calmodulin-1	P23458	JAK1	Tyrosine-protein kinase JAK1	0.822
P0DP24	CALM2	Calmodulin-2	P23458	JAK1	Tyrosine-protein kinase JAK1	0.738
P0DP23	CALM1	Calmodulin-1	P08238	HSP90AB1	Heat shock protein HSP 90-beta	0.775
P0DP25	CALM3	Calmodulin-3	P08238	HSP90AB1	Heat shock protein HSP 90-beta	0.775
P0DP24	CALM2	Calmodulin-2	P08238	HSP90AB1	Heat shock protein HSP 90-beta	0.775
P0DP23	CALM1	Calmodulin-1	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP25	CALM3	Calmodulin-3	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP24	CALM2	Calmodulin-2	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.775
P0DP23	CALM1	Calmodulin-1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
P0DP25	CALM3	Calmodulin-3	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
P0DP24	CALM2	Calmodulin-2	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.744
P0DP23	CALM1	Calmodulin-1	Q15311	RALBP1	RalA-binding protein 1	0.858
P46091	GPR1	Chemerin-like receptor 2	Q9UJU2	LEF1	Lymphoid enhancer-binding factor 1	0.736
P0DP23	CALM1	Calmodulin-1	P17252	PRKCA	Protein kinase C alpha type	-0.776
P46091	GPR1	Chemerin-like receptor 2	P17252	PRKCA	Protein kinase C alpha type	0.741
P0DP25	CALM3	Calmodulin-3	P17252	PRKCA	Protein kinase C alpha type	-0.776
P0DP24	CALM2	Calmodulin-2	P17252	PRKCA	Protein kinase C alpha type	-0.776
P0DP23	CALM1	Calmodulin-1	P43246	MSH2	DNA mismatch repair protein Msh2	0.944
P46091	GPR1	Chemerin-like receptor 2	P43246	MSH2	DNA mismatch repair protein Msh2	-0.838
P0DP25	CALM3	Calmodulin-3	P43246	MSH2	DNA mismatch repair protein Msh2	0.944
P0DP24	CALM2	Calmodulin-2	P43246	MSH2	DNA mismatch repair protein Msh2	0.944
P0DP23	CALM1	Calmodulin-1	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	0.777
P46091	GPR1	Chemerin-like receptor 2	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	-0.809
P0DP25	CALM3	Calmodulin-3	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	0.777
P0DP24	CALM2	Calmodulin-2	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	0.777
P0DP23	CALM1	Calmodulin-1	P14923	JUP	Junction plakoglobin	-0.852
P46091	GPR1	Chemerin-like receptor 2	P14923	JUP	Junction plakoglobin	0.883
P0DP25	CALM3	Calmodulin-3	P14923	JUP	Junction plakoglobin	-0.852
P0DP24	CALM2	Calmodulin-2	P14923	JUP	Junction plakoglobin	-0.852
P0DP23	CALM1	Calmodulin-1	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P46091	GPR1	Chemerin-like receptor 2	P10415	BCL2	Apoptosis regulator Bcl-2	0.808
P0DP25	CALM3	Calmodulin-3	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP24	CALM2	Calmodulin-2	P10415	BCL2	Apoptosis regulator Bcl-2	-0.772
P0DP23	CALM1	Calmodulin-1	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P46091	GPR1	Chemerin-like receptor 2	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	0.759
P0DP25	CALM3	Calmodulin-3	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P0DP24	CALM2	Calmodulin-2	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.8
P0DP23	CALM1	Calmodulin-1	P49767	VEGFC	Vascular endothelial growth factor C	-0.84
P46091	GPR1	Chemerin-like receptor 2	P49767	VEGFC	Vascular endothelial growth factor C	0.718
P0DP25	CALM3	Calmodulin-3	P49767	VEGFC	Vascular endothelial growth factor C	-0.84
P0DP24	CALM2	Calmodulin-2	P49767	VEGFC	Vascular endothelial growth factor C	-0.84
P0DP23	CALM1	Calmodulin-1	P31751	AKT2	RAC-beta serine/threonine-protein kinase	0.761
P46091	GPR1	Chemerin-like receptor 2	P25116	F2R	Proteinase-activated receptor 1	0.76
P0DP23	CALM1	Calmodulin-1	Q08828	ADCY1	Adenylate cyclase type 1	0.725
P0DP24	CALM2	Calmodulin-2	Q08828	ADCY1	Adenylate cyclase type 1	0.711
P0DP23	CALM1	Calmodulin-1	P51828	ADCY7	Adenylate cyclase type 7	0.719
P0DP23	CALM1	Calmodulin-1	P62873	GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	0.853
P0DP25	CALM3	Calmodulin-3	P62873	GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	0.853
P0DP24	CALM2	Calmodulin-2	P62873	GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	0.853
P0DP24	CALM2	Calmodulin-2	P61073	CXCR4	C-X-C chemokine receptor type 4	0.759
P0DP23	CALM1	Calmodulin-1	P78417	GSTO1	Glutathione S-transferase omega-1	-0.804
P46091	GPR1	Chemerin-like receptor 2	P78417	GSTO1	Glutathione S-transferase omega-1	0.738
P0DP25	CALM3	Calmodulin-3	P78417	GSTO1	Glutathione S-transferase omega-1	-0.804
P0DP24	CALM2	Calmodulin-2	P78417	GSTO1	Glutathione S-transferase omega-1	-0.804
P0DP23	CALM1	Calmodulin-1	O75293	GADD45B	Growth arrest and DNA damage-inducible protein GADD45 beta	-0.853
P0DP25	CALM3	Calmodulin-3	O75293	GADD45B	Growth arrest and DNA damage-inducible protein GADD45 beta	-0.853
P0DP24	CALM2	Calmodulin-2	O75293	GADD45B	Growth arrest and DNA damage-inducible protein GADD45 beta	-0.853
P0DP24	CALM2	Calmodulin-2	Q15788	NCOA1	Nuclear receptor coactivator 1	0.731
P0DP23	CALM1	Calmodulin-1	P0DP23	CALM1	Calmodulin-1	1
P46091	GPR1	Chemerin-like receptor 2	P0DP23	CALM1	Calmodulin-1	-0.846
P0DP25	CALM3	Calmodulin-3	P0DP23	CALM1	Calmodulin-1	1
P0DP24	CALM2	Calmodulin-2	P0DP23	CALM1	Calmodulin-1	1
P0DP24	CALM2	Calmodulin-2	Q13557	CAMK2D	Calcium/calmodulin-dependent protein kinase type II subunit delta	0.786
P0DP24	CALM2	Calmodulin-2	O43521	BCL2L11	Bcl-2-like protein 11	0.75
P0DP23	CALM1	Calmodulin-1	P01568	IFNA21	Interferon alpha-21	-0.852
P46091	GPR1	Chemerin-like receptor 2	P01568	IFNA21	Interferon alpha-21	0.724
P0DP25	CALM3	Calmodulin-3	P01568	IFNA21	Interferon alpha-21	-0.852
P0DP24	CALM2	Calmodulin-2	P01568	IFNA21	Interferon alpha-21	-0.852
P0DP23	CALM1	Calmodulin-1	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.801
P0DP25	CALM3	Calmodulin-3	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.801
P0DP24	CALM2	Calmodulin-2	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.801
P0DP23	CALM1	Calmodulin-1	P16871	IL7R	Interleukin-7 receptor subunit alpha	0.718
P0DP23	CALM1	Calmodulin-1	P00734	F2	Prothrombin	-0.738
P0DP23	CALM1	Calmodulin-1	P01042	KNG1	Kininogen-1	-0.71
P0DP25	CALM3	Calmodulin-3	P01042	KNG1	Kininogen-1	-0.71
P0DP24	CALM2	Calmodulin-2	P01042	KNG1	Kininogen-1	-0.71

Loperamide

hsa05202

Transcriptional misregulation in cancer

1.90E-05

Q15532, P41732, P14780, P27930, P14923, Q16548, P11215, Q13077, O15550, P35226, P05164, P12838, P08246, Q9C0K0, P41182, Q13547, Q92769, P12980, P24522

SS18, TSPAN7, MMP9, IL1R2, JUP, BCL2A1, ITGAM, TRAF1, UTX, BMI1, MPO, DEFA4, ELA2, BCL11B, BCL6, HDAC1, HDAC2, LYL1, GADD45A

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P22748	CA4	Carbonic anhydrase 4	Q15532	SS18	Protein SSXT	-0.862
P22748	CA4	Carbonic anhydrase 4	P41732	TSPAN7	Tetraspanin-7	0.706
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P41732	TSPAN7	Tetraspanin-7	0.703
P22748	CA4	Carbonic anhydrase 4	P14780	MMP9	Matrix metalloproteinase-9	0.925
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P14780	MMP9	Matrix metalloproteinase-9	0.942
O15245	SLC22A1	Solute carrier family 22 member 1	P27930	IL1R2	Interleukin-1 receptor type 2	0.711
P22748	CA4	Carbonic anhydrase 4	P27930	IL1R2	Interleukin-1 receptor type 2	0.708
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P27930	IL1R2	Interleukin-1 receptor type 2	0.924
P22748	CA4	Carbonic anhydrase 4	P14923	JUP	Junction plakoglobin	-0.772
P22748	CA4	Carbonic anhydrase 4	Q16548	BCL2A1	Bcl-2-related protein A1	0.833
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16548	BCL2A1	Bcl-2-related protein A1	0.913
O15245	SLC22A1	Solute carrier family 22 member 1	P11215	ITGAM	Integrin alpha-M	0.706
P22748	CA4	Carbonic anhydrase 4	Q13077	TRAF1	TNF receptor-associated factor 1	-0.718
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q13077	TRAF1	TNF receptor-associated factor 1	-0.712
P22748	CA4	Carbonic anhydrase 4	O15550	UTX	Lysine-specific demethylase 6A	0.714
P22748	CA4	Carbonic anhydrase 4	P35226	BMI1	Polycomb complex protein BMI-1	-0.834
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P35226	BMI1	Polycomb complex protein BMI-1	-0.778
P22748	CA4	Carbonic anhydrase 4	P35226	BMI1	Polycomb complex protein BMI-1	-0.834
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P35226	BMI1	Polycomb complex protein BMI-1	-0.778
P22748	CA4	Carbonic anhydrase 4	P05164	MPO	Myeloperoxidase	0.826
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P05164	MPO	Myeloperoxidase	0.711
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P12838	DEFA4	Neutrophil defensin 4	0.767
P22748	CA4	Carbonic anhydrase 4	P08246	ELA2	Neutrophil elastase	0.921
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P08246	ELA2	Neutrophil elastase	0.703
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q9C0K0	BCL11B	B-cell lymphoma/leukemia 11B	-0.765
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P41182	BCL6	B-cell lymphoma 6 protein	0.9
O15245	SLC22A1	Solute carrier family 22 member 1	Q13547	HDAC1	Histone deacetylase 1	-0.711
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q13547	HDAC1	Histone deacetylase 1	-0.742
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q92769	HDAC2	Histone deacetylase 2	-0.746
O15245	SLC22A1	Solute carrier family 22 member 1	P12980	LYL1	Protein lyl-1	0.806
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P12980	LYL1	Protein lyl-1	0.782
P22748	CA4	Carbonic anhydrase 4	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.769
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.801

Loperamide

hsa05203

Viral carcinogenesis

1.22E-03

Q13547, Q15283, P58876, P62807, Q16778, O60814

HDAC1, RASA2, H2BC5, HIST1H2BC, HIST2H2BE, H2BC12

Loperamide

hsa05204

Chemical carcinogenesis

2.59E-04

P00325, P78417, P11712, P33260

ADH1B, GSTO1, CYP2C9, CYP2C18

Loperamide

hsa05206

MicroRNAs in cancer

4.07E-02

P15311, P63279

VIL2, UBE2I

Loperamide

hsa05210

Colorectal cancer

1.78E-02

P84022, Q13485, P10415

SMAD3, SMAD4, BCL2

Loperamide

hsa05212

Pancreatic cancer

1.26E-04

P31751, Q15311, P23458, P42224, P37173, P84022, Q13485, O75293

AKT2, RALBP1, JAK1, STAT1, TGFBR2, SMAD3, SMAD4, GADD45B

Loperamide

hsa05214

Glioma

6.49E-08

P0DP23, Q16566, Q13557, P17252, P31751, P04637, P19174, P24522, O75293

CALM1, CAMK4, CAMK2D, PRKCA, AKT2, TP53, PLCG1, GADD45A, GADD45B

Loperamide

hsa05216

Thyroid cancer

1.85E-02

Q9UJU2, P04637, P24522

LEF1, TP53, GADD45A

Loperamide

hsa05217

Basal cell carcinoma

4.42E-02

Q9UJU2, P04637, P24522

LEF1, TP53, GADD45A

Loperamide

hsa05220

Chronic myeloid leukemia

1.25E-02

Q13485, P25963, P84022

SMAD4, NFKBIA, SMAD3

Loperamide

hsa05222

Small cell lung cancer

1.50E-02

Q13489, P10415, P25963

BIRC3, BCL2, NFKBIA

Loperamide

hsa05225

Hepatocellular carcinoma

4.07E-02

P60709, P63261

ACTB, ACTG1

Loperamide

hsa05226

Gastric cancer

2.78E-02

P84022, Q13485, P10415

SMAD3, SMAD4, BCL2

Loperamide

hsa05235

PD-L1 expression and PD-1 checkpoint pathway in cancer

8.27E-03

P42338, P19174, P07766, P20963, P06239, Q04759

PIK3CB, PLCG1, CD3E, CD247, LCK, PRKCQ

Loperamide

hsa05321

Inflammatory bowel disease

2.22E-03

O60603, P01375, P13765, Q14765, Q9UL17, P23771

TLR2, TNF, HLA-DOB, STAT4, TBX21, GATA3

Loperamide

hsa05322

Systemic lupus erythematosus

4.80E-06

P09871, Q93077, P58876, P62807, Q16778, O60814, P68431

C1S, HIST1H2AC, H2BC5, HIST1H2BC, HIST2H2BE, H2BC12, H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12

Loperamide

hsa05330

Allograft rejection

2.72E-02

P48023, P01375

FASLG, TNF

Loperamide

hsa05332

Graft-versus-host disease

3.34E-03

P13765, P48023, P01375, P26715, Q13241

HLA-DOB, FASLG, TNF, KLRC1, KLRD1

Loperamide

hsa05340

Primary immunodeficiency

2.68E-02

P11912, P07766

CD79A, CD3E

Loperamide

hsa05410

Hypertrophic cardiomyopathy

1.18E-03

P26012, P09493, P60709, P63261

ITGB8, TPM1, ACTB, ACTG1

Loperamide

hsa05412

Arrhythmogenic right ventricular cardiomyopathy

1.58E-04

P54284, P15924, P26012, P60709, P63261

CACNB3, DSP, ITGB8, ACTB, ACTG1

Loperamide

hsa05414

Dilated cardiomyopathy

1.73E-02

P60709, P63261

ACTB, ACTG1

Loperamide

hsa05415

Diabetic cardiomyopathy

1.28E-02

Q16718, O14521, Q16539, P49841

NDUFA5, SDHD, MAPK14, GSK3B

Loperamide

hsa05416

Viral myocarditis

8.96E-03

P60709, P63261

ACTB, ACTG1

Loperamide

hsa05418

Fluid shear stress and atherosclerosis

4.58E-05

Q16539, P14598, P78417, P10599, P14780, P01375, P60709, P63261, P10415, P14778, P27930, P0DP23, P08238, Q92974

MAPK14, NCF1, GSTO1, TXN, MMP9, TNF, ACTB, ACTG1, BCL2, IL1R1, IL1R2, CALM1, HSP90AB1, ARHGEF2

Community members of Loperamide (S_DC: 4.91)

UniProtAC

Gene Name

Protein Name

Reported/
Predicted

S_PV

CALM1

CalmodulinNone1

Reported

0.4552

0.1479

1.5235

O15245

SLC22A1

Solute carrier family 22 member 1

Predicted

0.0149

0.0219

2.0294

Q02763

TEK

AngiopoietinNone1 receptor

Predicted

0.3206

0.6236

0.4304

1.8379

P08183

ABCB1

ATPNonedependent translocase ABCB1

Predicted

0.0788

0.2052

2.2446

P31645

SLC6A4

SodiumNonedependent serotonin transporter

Predicted

0.0477

0.0203

2.0442

P00918

CA2

Carbonic anhydrase 2

Predicted

0.1125

0.2215

2.2778

P22748

CA4

Carbonic anhydrase 4

Predicted

0.0056

0.8267

0.1609

1.8171

P14416

DRD2

D(2) dopamine receptor

Predicted

0.0604

0.4779

2.5081

P21730

C5AR1

C5a anaphylatoxin chemotactic receptor 1

Predicted

0.0258

0.2167

0.5396

0.986

P50052

AGTR2

TypeNone2 angiotensin II receptor

Predicted

0.0604

0.4365

0.1541

1.0572

P22001

KCNA3

Potassium voltageNonegated channel subfamily A member 3

Predicted

0.1396

0.5055

1.0809

Q13547

HDAC1

Histone deacetylase 1

Predicted

0.0447

0.986

3.0084

P11712

CYP2C9

Cytochrome P450 2C9

Predicted

0.0106

0.1524

2.1577

O75381

PEX14

Peroxisomal membrane protein PEX14

Predicted

0.1907

0.0995

0.1097

0.4039

P00734

Prothrombin

Predicted

0.0963

0.707

0.4977

1.9598

P0DP25

CALM3

CalmodulinNone3

Predicted

0.5661

0.1479

0.5789

P0DP24

CALM2

CalmodulinNone2

Predicted

0.4376

0.1479

0.5147

O75469

NR1I2

Nuclear receptor subfamily 1 group I member 2

Predicted

0.0315

0.9493

1.9143

Q13133

NR1H3

Oxysterols receptor LXRNonealpha

Predicted

0.0162

0.439

0.2086

1.0947

P60660

MYL6

Myosin light polypeptide 6

Predicted

0.5595

0.0687

0.2175

0.6346

P50052

AGTR2

TypeNone2 angiotensin II receptor

Predicted

0.0604

0.4365

0.1541

1.0572

P24844

MYL9

Myosin regulatory light polypeptide 9

Predicted

0.0064

0.063

0.6026

0.7318

P14649

MYL6B

Myosin light chain 6B

Predicted

0.0477

0.0653

0.2175

0.3719

P21462

FPR1

fMetNoneLeuNonePhe receptor

Predicted

0.1205

0.3492

0.4378

1.1964

P25025

CXCR2

CNoneXNoneC chemokine receptor type 2

Predicted

0.0278

0.5189

0.4494

1.5011

P25024

CXCR1

CNoneXNoneC chemokine receptor type 1

Predicted

0.1656

0.4232

0.4009

1.33

P05976

MYL1

Myosin light chain 1/3, skeletal muscle isoform

Predicted

0.2581

0.0619

0.2528

O15182

CETN3

CentrinNone3

Predicted

0.1872

0.0594

0.2123

P51684

CCR6

CNoneC chemokine receptor type 6

Predicted

0.085

0.1741

0.3304

0.7212

P46091

GPR1

ChemerinNonelike receptor 2

Predicted

0.2476

0.1372

0.3982

Q96A32

MYLPF

Myosin regulatory light chain 2, skeletal muscle isoform

Predicted

0.0135

0.0473

0.5412

0.6425

PharmaCoNets of Loperamide (SPCN: 106.31 )

Loperamide regulated-network (SDN: 21.65)

Community members of Loperamide (SDC: 4.91)

PharmaCoNets of Loperamide (S_PCN: 106.31 )

Loperamide regulated-network (S_DN: 21.65)

Community members of Loperamide (S_DC: 4.91)