PharmaCoNets

PharmaCoNets of Tolvaptan (S_PCN: 131.17 )

Tolvaptan regulated-network (S_DN: 17.89)

Drug Name

Pathway ID

Pathway name

P-value

No. of gene members

UniProt AC

Gene name

Detail of Coexpression

Tolvaptan

hsa00030

Pentose phosphate pathway

7.65E-04

P06744, P60891, P37837

GPI, PRPS1, TALDO1

Tolvaptan

hsa00061

Fatty acid biosynthesis

4.83E-02

P33121

ACSL1

Tolvaptan

hsa00190

Oxidative phosphorylation

2.29E-02

Q16718, O14521

NDUFA5, SDHD

Tolvaptan

hsa00220

Arginine biosynthesis

3.83E-02

P05089, P49448

ARG1, GLUD2

Tolvaptan

hsa00310

Lysine degradation

2.59E-02

Q96KQ7, P51648

EHMT2, ALDH3A2

Tolvaptan

hsa00500

Starch and sucrose metabolism

1.33E-03

O43451, P46976, P06737

MGAM, GYG1, PYGL

Tolvaptan

hsa00512

Mucin type O-glycan biosynthesis

4.86E-02

O95395, Q9NY28

GCNT3, GALNT8

Tolvaptan

hsa00513

Various types of N-glycan biosynthesis

4.83E-02

Q9NR34

MAN1C1

Tolvaptan

hsa00520

Amino sugar and nucleotide sugar metabolism

2.24E-02

Q16222, Q9Y223, P06865

UAP1, GNE, HEXA

Tolvaptan

hsa00590

Arachidonic acid metabolism

3.85E-02

P11712, P09960

CYP2C9, LTA4H

Tolvaptan

hsa00591

Linoleic acid metabolism

1.95E-03

P11712

CYP2C9

Tolvaptan

hsa00630

Glyoxylate and dicarboxylate metabolism

9.62E-04

P40925, P40926, P15104

MDH1, MDH2, GLUL

Tolvaptan

hsa00730

Thiamine metabolism

2.43E-03

P05186, P24666

ALPL, ACP1

Tolvaptan

hsa00830

Retinol metabolism

4.01E-03

P00352, Q9BPW9, O75911, P11712

ALDH1A1, DHRS9, DHRS3, CYP2C9

Tolvaptan

hsa00860

Porphyrin and chlorophyll metabolism

1.69E-02

P36551, P30043

CPOX, BLVRB

Tolvaptan

hsa00980

Metabolism of xenobiotics by cytochrome P450

9.14E-03

P78417, P11712

GSTO1, CYP2C9

Tolvaptan

hsa00982

Drug metabolism - cytochrome P450

9.14E-03

P11712, P78417

CYP2C9, GSTO1

Tolvaptan

hsa01100

Metabolic pathways

4.43E-02

Q9NR34, P05089, P32320, P22748, P55809, P06280, Q16875, O43286, O43451, P05186, P24666, Q9HCC0, P33121, P57054, Q9UNP4, Q9BX95, P32321, Q9BPW9, O75911, Q9UHY7, P43490, P46976, P06737

MAN1C1, ARG1, CDA, CA4, OXCT1, GLA, PFKFB3, B4GALT5, MGAM, ALPL, ACP1, MCCC2, ACSL1, PIGP, ST3GAL5, SGPP1, DCTD, DHRS9, DHRS3, ENOPH1, PBEF1, GYG1, PYGL

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
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q9NR34	MAN1C1	Mannosyl-oligosaccharide 1,2-alpha-mannosidase IC	-0.716
Q16539	MAPK14	Mitogen-activated protein kinase 14	P05089	ARG1	Arginase-1	0.702
Q16539	MAPK14	Mitogen-activated protein kinase 14	P32320	CDA	Cytidine deaminase	0.701
Q16539	MAPK14	Mitogen-activated protein kinase 14	P22748	CA4	Carbonic anhydrase 4	0.767
Q16539	MAPK14	Mitogen-activated protein kinase 14	P55809	OXCT1	Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial	-0.746
Q16539	MAPK14	Mitogen-activated protein kinase 14	P06280	GLA	Alpha-galactosidase A	0.714
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q16875	PFKFB3	6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3	0.849
Q16539	MAPK14	Mitogen-activated protein kinase 14	O43286	B4GALT5	Beta-1,4-galactosyltransferase 5	0.917
Q16539	MAPK14	Mitogen-activated protein kinase 14	O43451	MGAM	Maltase-glucoamylase	0.871
Q16539	MAPK14	Mitogen-activated protein kinase 14	P05186	ALPL	Alkaline phosphatase, tissue-nonspecific isozyme	0.901
Q16539	MAPK14	Mitogen-activated protein kinase 14	P24666	ACP1	Low molecular weight phosphotyrosine protein phosphatase	-0.832
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q9HCC0	MCCC2	Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial	-0.782
Q16539	MAPK14	Mitogen-activated protein kinase 14	P33121	ACSL1	Long-chain-fatty-acid--CoA ligase 1	0.886
Q16539	MAPK14	Mitogen-activated protein kinase 14	P57054	PIGP	Phosphatidylinositol N-acetylglucosaminyltransferase subunit P	-0.881
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q9UNP4	ST3GAL5	Lactosylceramide alpha-2,3-sialyltransferase	-0.819
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q9BX95	SGPP1	Sphingosine-1-phosphate phosphatase 1	-0.743
Q16539	MAPK14	Mitogen-activated protein kinase 14	P32321	DCTD	Deoxycytidylate deaminase	-0.748
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q9BPW9	DHRS9	Dehydrogenase/reductase SDR family member 9	0.817
Q16539	MAPK14	Mitogen-activated protein kinase 14	O75911	DHRS3	Short-chain dehydrogenase/reductase 3	-0.81
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q9UHY7	ENOPH1	Enolase-phosphatase E1	-0.737
Q16539	MAPK14	Mitogen-activated protein kinase 14	P43490	PBEF1	Nicotinamide phosphoribosyltransferase	0.883
Q16539	MAPK14	Mitogen-activated protein kinase 14	P46976	GYG1	Glycogenin-1	0.817
Q16539	MAPK14	Mitogen-activated protein kinase 14	P06737	PYGL	Glycogen phosphorylase, liver form	0.863

Tolvaptan

hsa01200

Carbon metabolism

7.69E-03

P06744, P37837, P40926

GPI, TALDO1, MDH2

Tolvaptan

hsa01230

Biosynthesis of amino acids

3.59E-02

P60891, Q99707, P37837

PRPS1, MTR, TALDO1

Tolvaptan

hsa01523

Antifolate resistance

2.04E-02

P04818, P18054

TYMS, ALOX12

Tolvaptan

hsa01524

Platinum drug resistance

4.42E-02

P10415, Q13489, P23025

BCL2, BIRC3, XPA

Tolvaptan

hsa02010

ABC transporters

1.98E-03

P45844, P08183, Q8IZY2

ABCG1, ABCB1, ABCA7

Tolvaptan

hsa03008

Ribosome biogenesis in eukaryotes

1.88E-02

O14980, O60832, Q9BVP2

XPO1, DKC1, GNL3

Tolvaptan

hsa03013

RNA transport

6.93E-08

O14980, P52298, O14893, P61326, Q15287, Q9UBU9, Q7Z3B4, P35658, P63279, Q14152, P55884, O15371, P20042, Q14240, P23588, Q9Y6A5

XPO1, NCBP2, GEMIN2, MAGOH, RNPS1, NXF1, NUP54, NUP214, UBE2I, EIF3A, EIF3B, EIF3D, EIF2S2, EIF4A2, EIF4B, TACC3

Tolvaptan

hsa03022

Basal transcription factors

3.32E-02

O00268, Q15544

TAF4, TAF11

Tolvaptan

hsa03040

Spliceosome

5.33E-05

Q14562, O43143, O60508, P17844, Q15427, P51991, P38159, P61978, Q07955, Q01130, Q13243, P11142

DHX8, DHX15, CDC40, DDX5, SF3B4, HNRPA3, RBMX, HNRPK, SFRS1, SFRS2, SFRS5, HSPA8

Tolvaptan

hsa03060

Protein export

1.43E-02

P37108, Q15005

SRP14, SPCS2

Tolvaptan

hsa03320

PPAR signaling pathway

4.55E-02

O00767, Q02318

SCD, CYP27A1

Tolvaptan

hsa04012

ErbB signaling pathway

3.74E-02

P21860, Q13557, O14944

ERBB3, CAMK2D, EREG

Tolvaptan

hsa04014

Ras signaling pathway

8.19E-04

Q9NRA1, Q13009, Q15283, P61586, P0DP23, P62873, P63218, P50151, P19174

PDGFC, TIAM1, RASA2, RHOA, CALM1, GNB1, GNG5, GNG10, PLCG1

Tolvaptan

hsa04020

Calcium signaling pathway

6.50E-04

Q96DU7, P45880, Q13557, P21860, P51828, P23634

ITPKC, VDAC2, CAMK2D, ERBB3, ADCY7, ATP2B4

Tolvaptan

hsa04022

cGMP-PKG signaling pathway

4.72E-02

Q99941, P23634, P51828, P45880

CREBL1, ATP2B4, ADCY7, VDAC2

Tolvaptan

hsa04060

Cytokine-cytokine receptor interaction

5.34E-03

P14784, P27930, P14778, P26842, Q06643, Q13651, P25024, Q9UBD3, P47992, P09341, P01730

IL2RB, IL1R2, IL1R1, CD27, LTB, IL10RA, CXCR1, XCL2, XCL1, CXCL1, CD4

Tolvaptan

hsa04061

Viral protein interaction with cytokine and cytokine receptor

2.01E-04

P09341, P19875, P25024, P02775, P25025, P47992, Q9UBD3, Q13651, P14784

CXCL1, CXCL2, CXCR1, PPBP, CXCR2, XCL1, XCL2, IL10RA, IL2RB

Tolvaptan

hsa04062

Chemokine signaling pathway

2.97E-06

P25024, P25025, P09341, P19875, P47992, Q9UBD3, P07948, P42338, P19174, P62873, P63218, P50151, P43250, Q08881, Q13009, P14598, P42224, P25963

CXCR1, CXCR2, CXCL1, CXCL2, XCL1, XCL2, LYN, PIK3CB, PLCG1, GNB1, GNG5, GNG10, GRK6, ITK, TIAM1, NCF1, STAT1, NFKBIA

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
P06239	LCK	Tyrosine-protein kinase Lck	P25024	CXCR1	C-X-C chemokine receptor type 1	-0.779
Q13547	HDAC1	Histone deacetylase 1	P25024	CXCR1	C-X-C chemokine receptor type 1	-0.803
Q13547	HDAC1	Histone deacetylase 1	P25025	CXCR2	C-X-C chemokine receptor type 2	-0.719
P06239	LCK	Tyrosine-protein kinase Lck	P09341	CXCL1	Growth-regulated alpha protein	-0.805
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
P06239	LCK	Tyrosine-protein kinase Lck	P47992	XCL1	Lymphotactin	0.715
P06239	LCK	Tyrosine-protein kinase Lck	Q9UBD3	XCL2	Cytokine SCM-1 beta	0.715
P06239	LCK	Tyrosine-protein kinase Lck	P07948	LYN	Tyrosine-protein kinase Lyn	-0.701
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P07948	LYN	Tyrosine-protein kinase Lyn	-0.782
Q13547	HDAC1	Histone deacetylase 1	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.774
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.869
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P62873	GNB1	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	0.82
P06239	LCK	Tyrosine-protein kinase Lck	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	-0.728
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	-0.703
Q13547	HDAC1	Histone deacetylase 1	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	-0.864
P06239	LCK	Tyrosine-protein kinase Lck	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	-0.71
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	-0.704
Q13547	HDAC1	Histone deacetylase 1	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	-0.716
P06239	LCK	Tyrosine-protein kinase Lck	P43250	GRK6	G protein-coupled receptor kinase 6	-0.702
P06239	LCK	Tyrosine-protein kinase Lck	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	0.774
P08238	HSP90AB1	Heat shock protein HSP 90-beta	Q13009	TIAM1	Rho guanine nucleotide exchange factor TIAM1	-0.746
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P14598	NCF1	Neutrophil cytosol factor 1	0.785
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.783
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P25963	NFKBIA	NF-kappa-B inhibitor alpha	0.818

Tolvaptan

hsa04064

NF-kappa B signaling pathway

9.61E-10

P10415, Q13489, O00463, Q13546, P14778, P01375, P19174, Q04759, Q9UDY8, Q13077, Q16548, P07948, P06239, Q8WV28, Q13315, P24522, P09341, P19875, Q06643, Q9UNE0

BCL2, BIRC3, TRAF5, RIPK1, IL1R1, TNF, PLCG1, PRKCQ, MALT1, TRAF1, BCL2A1, LYN, LCK, BLNK, ATM, GADD45A, CXCL1, CXCL2, LTB, EDAR

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
P06737	PYGL	Glycogen phosphorylase, liver form	P10415	BCL2	Apoptosis regulator Bcl-2	-0.766
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	P10415	BCL2	Apoptosis regulator Bcl-2	-0.706
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P10415	BCL2	Apoptosis regulator Bcl-2	0.713
P08235	NR3C2	Mineralocorticoid receptor	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	0.868
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.832
P06737	PYGL	Glycogen phosphorylase, liver form	O00463	TRAF5	TNF receptor-associated factor 5	-0.924
Q16539	MAPK14	Mitogen-activated protein kinase 14	O00463	TRAF5	TNF receptor-associated factor 5	-0.837
P06239	LCK	Tyrosine-protein kinase Lck	O00463	TRAF5	TNF receptor-associated factor 5	0.718
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	O00463	TRAF5	TNF receptor-associated factor 5	0.717
P08235	NR3C2	Mineralocorticoid receptor	Q13546	RIPK1	Receptor-interacting serine/threonine-protein kinase 1	-0.749
Q16539	MAPK14	Mitogen-activated protein kinase 14	P14778	IL1R1	Interleukin-1 receptor type 1	0.76
P06239	LCK	Tyrosine-protein kinase Lck	P14778	IL1R1	Interleukin-1 receptor type 1	-0.782
Q13547	HDAC1	Histone deacetylase 1	P14778	IL1R1	Interleukin-1 receptor type 1	-0.854
P06737	PYGL	Glycogen phosphorylase, liver form	P01375	TNF	Tumor necrosis factor	0.759
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
P06737	PYGL	Glycogen phosphorylase, liver form	Q04759	PRKCQ	Protein kinase C theta type	-0.812
P06239	LCK	Tyrosine-protein kinase Lck	Q04759	PRKCQ	Protein kinase C theta type	0.779
Q13547	HDAC1	Histone deacetylase 1	Q04759	PRKCQ	Protein kinase C theta type	0.723
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q04759	PRKCQ	Protein kinase C theta type	0.776
P08235	NR3C2	Mineralocorticoid receptor	Q9UDY8	MALT1	Mucosa-associated lymphoid tissue lymphoma translocation protein 1	0.708
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q9UDY8	MALT1	Mucosa-associated lymphoid tissue lymphoma translocation protein 1	0.723
P06737	PYGL	Glycogen phosphorylase, liver form	Q13077	TRAF1	TNF receptor-associated factor 1	-0.783
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q13077	TRAF1	TNF receptor-associated factor 1	-0.73
P06737	PYGL	Glycogen phosphorylase, liver form	Q16548	BCL2A1	Bcl-2-related protein A1	0.967
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q16548	BCL2A1	Bcl-2-related protein A1	0.875
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	Q16548	BCL2A1	Bcl-2-related protein A1	0.751
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q16548	BCL2A1	Bcl-2-related protein A1	-0.701
P06239	LCK	Tyrosine-protein kinase Lck	P07948	LYN	Tyrosine-protein kinase Lyn	-0.701
P06239	LCK	Tyrosine-protein kinase Lck	P06239	LCK	Tyrosine-protein kinase Lck	1
Q13547	HDAC1	Histone deacetylase 1	P06239	LCK	Tyrosine-protein kinase Lck	0.811
P06737	PYGL	Glycogen phosphorylase, liver form	Q8WV28	BLNK	B-cell linker protein	-0.706
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q8WV28	BLNK	B-cell linker protein	-0.816
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	Q8WV28	BLNK	B-cell linker protein	-0.746
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q13315	ATM	Serine-protein kinase ATM	0.723
P06737	PYGL	Glycogen phosphorylase, liver form	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.822
Q16539	MAPK14	Mitogen-activated protein kinase 14	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.796
P06239	LCK	Tyrosine-protein kinase Lck	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	-0.724
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	-0.734
P06737	PYGL	Glycogen phosphorylase, liver form	P09341	CXCL1	Growth-regulated alpha protein	0.74
Q16539	MAPK14	Mitogen-activated protein kinase 14	P09341	CXCL1	Growth-regulated alpha protein	0.7
P06239	LCK	Tyrosine-protein kinase Lck	P09341	CXCL1	Growth-regulated alpha protein	-0.805
Q13547	HDAC1	Histone deacetylase 1	P09341	CXCL1	Growth-regulated alpha protein	-0.736
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P09341	CXCL1	Growth-regulated alpha protein	-0.789
Q13547	HDAC1	Histone deacetylase 1	P19875	CXCL2	C-X-C motif chemokine 2	-0.862
P06239	LCK	Tyrosine-protein kinase Lck	Q06643	LTB	Lymphotoxin-beta	0.846
Q13547	HDAC1	Histone deacetylase 1	Q06643	LTB	Lymphotoxin-beta	0.74
P08235	NR3C2	Mineralocorticoid receptor	Q9UNE0	EDAR	Tumor necrosis factor receptor superfamily member EDAR	0.819

Tolvaptan

hsa04070

Phosphatidylinositol signaling system

2.37E-03

P19174, P0DP23, P23743, Q86XP1, P27987, Q96DU7

PLCG1, CALM1, DGKA, DGKH, ITPKB, ITPKC

Tolvaptan

hsa04071

Sphingolipid signaling pathway

4.34E-06

P21453, Q9H228, P01375, Q13362, Q9BX95, Q16539, P10415, Q9UQC2, P01042

S1PR1, EDG8, TNF, PPP2R5C, SGPP1, MAPK14, 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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P21453	S1PR1	Sphingosine 1-phosphate receptor 1	0.934
P06737	PYGL	Glycogen phosphorylase, liver form	Q9H228	EDG8	Sphingosine 1-phosphate receptor 5	-0.841
P14780	MMP9	Matrix metalloproteinase-9	Q9H228	EDG8	Sphingosine 1-phosphate receptor 5	-0.901
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q9H228	EDG8	Sphingosine 1-phosphate receptor 5	0.777
P06737	PYGL	Glycogen phosphorylase, liver form	P01375	TNF	Tumor necrosis factor	0.759
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P06737	PYGL	Glycogen phosphorylase, liver form	Q13362	PPP2R5C	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform	-0.716
P14780	MMP9	Matrix metalloproteinase-9	Q13362	PPP2R5C	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform	-0.828
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q13362	PPP2R5C	Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform	0.721
P06737	PYGL	Glycogen phosphorylase, liver form	Q9BX95	SGPP1	Sphingosine-1-phosphate phosphatase 1	-0.781
P14780	MMP9	Matrix metalloproteinase-9	Q9BX95	SGPP1	Sphingosine-1-phosphate phosphatase 1	-0.869
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q9BX95	SGPP1	Sphingosine-1-phosphate phosphatase 1	0.7
P06737	PYGL	Glycogen phosphorylase, liver form	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.863
P14780	MMP9	Matrix metalloproteinase-9	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.778
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.708
P06737	PYGL	Glycogen phosphorylase, liver form	P10415	BCL2	Apoptosis regulator Bcl-2	-0.766
P14780	MMP9	Matrix metalloproteinase-9	P10415	BCL2	Apoptosis regulator Bcl-2	-0.765
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	P10415	BCL2	Apoptosis regulator Bcl-2	-0.706
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P10415	BCL2	Apoptosis regulator Bcl-2	0.713
P06737	PYGL	Glycogen phosphorylase, liver form	Q9UQC2	GAB2	GRB2-associated-binding protein 2	0.822
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	Q9UQC2	GAB2	GRB2-associated-binding protein 2	0.708
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	P01042	KNG1	Kininogen-1	-0.773

Tolvaptan

hsa04072

Phospholipase D signaling pathway

4.48E-02

P42338, P43657, P25024, P25025, P19174

PIK3CB, P2RY5, CXCR1, CXCR2, PLCG1

Tolvaptan

hsa04080

Neuroactive ligand-receptor interaction

1.37E-04

P08311, Q15722, P21453, Q9H228, O00398, P25116, P21462, P21730, Q16581, P07550, P01042, P35318

CTSG, LTB4R, S1PR1, EDG8, P2RY10, F2R, FPR1, C5AR1, C3AR1, ADRB2, KNG1, ADM

Tolvaptan

hsa04136

Autophagy - other

5.92E-03

O94817, Q9H1Y0

ATG12, ATG5

Tolvaptan

hsa04140

Autophagy - animal

3.19E-02

P22694, Q14643, P10415, Q04759

PRKACB, ITPR1, BCL2, PRKCQ

Tolvaptan

hsa04141

Protein processing in endoplasmic reticulum

1.75E-05

P18848, P30101, Q15437, P60604, Q99941, O75460, P11142, Q9H3Z4, P07900, P08238, Q9NR31, Q9H173, Q9UNL2

ATF4, PDIA3, SEC23B, UBE2G2, CREBL1, ERN1, HSPA8, DNAJC5, HSP90AA1, HSP90AB1, SAR1A, SIL1, SSR3

Tolvaptan

hsa04145

Phagosome

9.44E-04

P11215, Q15080, P14598, Q71U36, Q13509, P68371, Q13488, P05164, O60603, P35443, P13765

ITGAM, NCF4, NCF1, TUBA1A, TUBB3, TUBB2C, TCIRG1, MPO, TLR2, THBS4, HLA-DOB

Tolvaptan

hsa04151

PI3K-Akt signaling pathway

3.91E-03

P62753, P27348, P07900, P22105, Q99941, P18848, O00141

RPS6, YWHAQ, HSP90AA1, TNXB, CREBL1, ATF4, SGK

Tolvaptan

hsa04210

Apoptosis

3.44E-02

Q13315, P10415, O76075, P24522, Q16548, P43234, Q14643

ATM, BCL2, DFFB, GADD45A, BCL2A1, CTSO, ITPR1

Tolvaptan

hsa04211

Longevity regulating pathway

9.85E-04

Q12778, P51828, Q99941, P18848, Q9UEF7, Q96KQ7

FOXO1, ADCY7, CREBL1, ATF4, KL, EHMT2

Tolvaptan

hsa04213

Longevity regulating pathway - multiple species

3.85E-02

P42338, Q9Y4H2, P11142, Q13547

PIK3CB, IRS2, HSPA8, HDAC1

Tolvaptan

hsa04215

Apoptosis - multiple species

3.01E-02

Q13489, P10415

BIRC3, BCL2

Tolvaptan

hsa04217

Necroptosis

2.93E-02

P01568, Q13489, Q13546

IFNA21, BIRC3, RIPK1

Tolvaptan

hsa04261

Adrenergic signaling in cardiomyocytes

1.68E-03

P51828, Q99941, P18848, Q13557, P23634

ADCY7, CREBL1, ATF4, CAMK2D, ATP2B4

Tolvaptan

hsa04330

Notch signaling pathway

4.34E-02

Q92542, P46531

NCSTN, NOTCH1

Tolvaptan

hsa04340

Hedgehog signaling pathway

8.75E-05

P49841, P22694, Q13635, P10415

GSK3B, PRKACB, PTCH1, BCL2

Tolvaptan

hsa04350

TGF-beta signaling pathway

4.88E-02

P37173

TGFBR2

Tolvaptan

hsa04371

Apelin signaling pathway

7.95E-04

P62873, P63218, P50151, Q13370, Q14344, P84022, P0DP23

GNB1, GNG5, GNG10, PDE3B, GNA13, SMAD3, CALM1

Tolvaptan

hsa04380

Osteoclast differentiation

1.81E-02

Q9UQC2, Q16539, Q8WV28, Q15080

GAB2, MAPK14, BLNK, NCF4

Tolvaptan

hsa04510

Focal adhesion

4.60E-02

P16144, Q15942, Q13489, P10415

ITGB4, ZYX, BIRC3, BCL2

Tolvaptan

hsa04530

Tight junction

2.45E-03

Q8TEU7, P16989, P56750, O00501, Q14247, P24844

RAPGEF6, CSDA, CLDN17, CLDN5, CTTN, MYL9

Tolvaptan

hsa04540

Gap junction

1.08E-02

Q13509, P68371, Q71U36, Q9NRA1

TUBB3, TUBB2C, TUBA1A, PDGFC

Tolvaptan

hsa04610

Complement and coagulation cascades

3.01E-06

P25116, P01042, P00734, P0C0L4, Q16581

F2R, KNG1, F2, C4A, C3AR1

Tolvaptan

hsa04612

Antigen processing and presentation

1.13E-05

P13765, P48382, P01730, P26715, P26717, Q13241, O43908, P01732, P01375

HLA-DOB, RFX5, CD4, KLRC1, KLRC2, KLRD1, KLRC4, CD8A, TNF

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
P14780	MMP9	Matrix metalloproteinase-9	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.714
P06239	LCK	Tyrosine-protein kinase Lck	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	0.777
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.73
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	0.795
P14780	MMP9	Matrix metalloproteinase-9	P48382	RFX5	DNA-binding protein RFX5	-0.874
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P48382	RFX5	DNA-binding protein RFX5	-0.738
P06239	LCK	Tyrosine-protein kinase Lck	P01730	CD4	T-cell surface glycoprotein CD4	0.746
P14780	MMP9	Matrix metalloproteinase-9	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	-0.867
P06239	LCK	Tyrosine-protein kinase Lck	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	0.756
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	-0.838
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	0.853
P14780	MMP9	Matrix metalloproteinase-9	P26717	KLRC2	NKG2-C type II integral membrane protein	-0.867
P06239	LCK	Tyrosine-protein kinase Lck	P26717	KLRC2	NKG2-C type II integral membrane protein	0.756
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P26717	KLRC2	NKG2-C type II integral membrane protein	-0.838
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P26717	KLRC2	NKG2-C type II integral membrane protein	0.853
P14780	MMP9	Matrix metalloproteinase-9	Q13241	KLRD1	Natural killer cells antigen CD94	-0.837
P06239	LCK	Tyrosine-protein kinase Lck	Q13241	KLRD1	Natural killer cells antigen CD94	0.758
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q13241	KLRD1	Natural killer cells antigen CD94	-0.856
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q13241	KLRD1	Natural killer cells antigen CD94	0.863
P14780	MMP9	Matrix metalloproteinase-9	O43908	KLRC4	NKG2-F type II integral membrane protein	-0.792
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O43908	KLRC4	NKG2-F type II integral membrane protein	-0.741
P14780	MMP9	Matrix metalloproteinase-9	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.742
P06239	LCK	Tyrosine-protein kinase Lck	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	0.841
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.816
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	0.92
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774

Tolvaptan

hsa04613

Neutrophil extracellular trap formation

6.36E-07

O60603, P05164, P08246, Q9UM07, Q13547, Q92769, P04908, Q6FI13, Q93077, P62807, O60814, P68431, Q15080, P20160, P08311, O75015, P21730, P21462, O43315, Q16539

TLR2, MPO, ELA2, PADI4, HDAC1, HDAC2, H2AC4; H2AC8, H2AC18; H2AC19, HIST1H2AC, HIST1H2BC, H2BC12, H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12, 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
P06737	PYGL	Glycogen phosphorylase, liver form	O60603	TLR2	Toll-like receptor 2	0.836
P14780	MMP9	Matrix metalloproteinase-9	O60603	TLR2	Toll-like receptor 2	0.89
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O60603	TLR2	Toll-like receptor 2	0.867
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	O60603	TLR2	Toll-like receptor 2	-0.717
P06737	PYGL	Glycogen phosphorylase, liver form	P05164	MPO	Myeloperoxidase	0.858
P14780	MMP9	Matrix metalloproteinase-9	P05164	MPO	Myeloperoxidase	0.812
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P05164	MPO	Myeloperoxidase	0.711
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P05164	MPO	Myeloperoxidase	-0.866
P06737	PYGL	Glycogen phosphorylase, liver form	P08246	ELA2	Neutrophil elastase	0.817
P14780	MMP9	Matrix metalloproteinase-9	P08246	ELA2	Neutrophil elastase	0.859
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P08246	ELA2	Neutrophil elastase	0.703
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P08246	ELA2	Neutrophil elastase	-0.76
P06737	PYGL	Glycogen phosphorylase, liver form	Q9UM07	PADI4	Protein-arginine deiminase type-4	0.813
P14780	MMP9	Matrix metalloproteinase-9	Q9UM07	PADI4	Protein-arginine deiminase type-4	0.9
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q9UM07	PADI4	Protein-arginine deiminase type-4	0.825
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q9UM07	PADI4	Protein-arginine deiminase type-4	-0.819
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
P31645	SLC6A4	Sodium-dependent serotonin transporter	P04908	H2AC4; H2AC8	Histone H2A type 1-B/E	0.734
P14780	MMP9	Matrix metalloproteinase-9	Q6FI13	H2AC18; H2AC19	Histone H2A type 2-A	0.74
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
P11712	CYP2C9	Cytochrome P450 2C9	P62807	HIST1H2BC	Histone H2B type 1-C/E/F/G/I	0.717
P11712	CYP2C9	Cytochrome P450 2C9	P62807	HIST1H2BC	Histone H2B type 1-C/E/F/G/I	0.717
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
P06737	PYGL	Glycogen phosphorylase, liver form	Q15080	NCF4	Neutrophil cytosol factor 4	0.836
P14780	MMP9	Matrix metalloproteinase-9	Q15080	NCF4	Neutrophil cytosol factor 4	0.869
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q15080	NCF4	Neutrophil cytosol factor 4	0.764
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q15080	NCF4	Neutrophil cytosol factor 4	-0.731
P06737	PYGL	Glycogen phosphorylase, liver form	P20160	AZU1	Azurocidin	0.781
P14780	MMP9	Matrix metalloproteinase-9	P20160	AZU1	Azurocidin	0.734
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P20160	AZU1	Azurocidin	-0.799
P06737	PYGL	Glycogen phosphorylase, liver form	P08311	CTSG	Cathepsin G	0.829
P14780	MMP9	Matrix metalloproteinase-9	P08311	CTSG	Cathepsin G	0.79
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P08311	CTSG	Cathepsin G	0.709
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P08311	CTSG	Cathepsin G	-0.811
P06737	PYGL	Glycogen phosphorylase, liver form	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.852
P14780	MMP9	Matrix metalloproteinase-9	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.928
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.893
P06737	PYGL	Glycogen phosphorylase, liver form	P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	0.888
P14780	MMP9	Matrix metalloproteinase-9	P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	0.942
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	1
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	-0.772
P06737	PYGL	Glycogen phosphorylase, liver form	P21462	FPR1	fMet-Leu-Phe receptor	0.833
P14780	MMP9	Matrix metalloproteinase-9	P21462	FPR1	fMet-Leu-Phe receptor	0.912
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P21462	FPR1	fMet-Leu-Phe receptor	0.842
P31645	SLC6A4	Sodium-dependent serotonin transporter	O43315	AQP9	Aquaporin-9	-0.764
P06737	PYGL	Glycogen phosphorylase, liver form	O43315	AQP9	Aquaporin-9	0.897
P14780	MMP9	Matrix metalloproteinase-9	O43315	AQP9	Aquaporin-9	0.837
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
P06737	PYGL	Glycogen phosphorylase, liver form	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.863
P14780	MMP9	Matrix metalloproteinase-9	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.778
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.833

Tolvaptan

hsa04614

Renin-angiotensin system

1.52E-02

P50052

AGTR2

Tolvaptan

hsa04620

Toll-like receptor signaling pathway

4.16E-02

Q13546, P01568

RIPK1, IFNA21

Tolvaptan

hsa04621

NOD-like receptor signaling pathway

5.89E-04

Q16539, Q14643, P01568, Q13489, P10599, Q9H1Y0, P43490, O00463, P10415, Q13546, Q05823, P01375, P09341, P12838

MAPK14, ITPR1, IFNA21, BIRC3, TXN, ATG5, PBEF1, TRAF5, BCL2, RIPK1, RNASEL, TNF, CXCL1, DEFA4

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
P06737	PYGL	Glycogen phosphorylase, liver form	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.863
P14780	MMP9	Matrix metalloproteinase-9	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.778
P06737	PYGL	Glycogen phosphorylase, liver form	Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	-0.804
P14780	MMP9	Matrix metalloproteinase-9	Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	-0.81
P08235	NR3C2	Mineralocorticoid receptor	P01568	IFNA21	Interferon alpha-21	0.757
P08235	NR3C2	Mineralocorticoid receptor	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	0.868
P06737	PYGL	Glycogen phosphorylase, liver form	P10599	TXN	Thioredoxin	0.764
P14780	MMP9	Matrix metalloproteinase-9	P10599	TXN	Thioredoxin	0.713
P06737	PYGL	Glycogen phosphorylase, liver form	Q9H1Y0	ATG5	Autophagy protein 5	-0.73
P14780	MMP9	Matrix metalloproteinase-9	Q9H1Y0	ATG5	Autophagy protein 5	-0.895
P06737	PYGL	Glycogen phosphorylase, liver form	P43490	PBEF1	Nicotinamide phosphoribosyltransferase	0.912
P14780	MMP9	Matrix metalloproteinase-9	P43490	PBEF1	Nicotinamide phosphoribosyltransferase	0.94
P06737	PYGL	Glycogen phosphorylase, liver form	O00463	TRAF5	TNF receptor-associated factor 5	-0.924
P14780	MMP9	Matrix metalloproteinase-9	O00463	TRAF5	TNF receptor-associated factor 5	-0.917
P06737	PYGL	Glycogen phosphorylase, liver form	P10415	BCL2	Apoptosis regulator Bcl-2	-0.766
P14780	MMP9	Matrix metalloproteinase-9	P10415	BCL2	Apoptosis regulator Bcl-2	-0.765
P08235	NR3C2	Mineralocorticoid receptor	Q13546	RIPK1	Receptor-interacting serine/threonine-protein kinase 1	-0.749
P14780	MMP9	Matrix metalloproteinase-9	Q05823	RNASEL	2-5A-dependent ribonuclease	0.73
P06737	PYGL	Glycogen phosphorylase, liver form	P01375	TNF	Tumor necrosis factor	0.759
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P06737	PYGL	Glycogen phosphorylase, liver form	P09341	CXCL1	Growth-regulated alpha protein	0.74
P14780	MMP9	Matrix metalloproteinase-9	P09341	CXCL1	Growth-regulated alpha protein	0.771
P06737	PYGL	Glycogen phosphorylase, liver form	P12838	DEFA4	Neutrophil defensin 4	0.7
P14780	MMP9	Matrix metalloproteinase-9	P12838	DEFA4	Neutrophil defensin 4	0.858

Tolvaptan

hsa04622

RIG-I-like receptor signaling pathway

2.39E-02

P01568, Q13546

IFNA21, RIPK1

Tolvaptan

hsa04623

Cytosolic DNA-sensing pathway

1.93E-04

P01568, Q13546, P25963

IFNA21, RIPK1, NFKBIA

Tolvaptan

hsa04625

C-type lectin receptor signaling pathway

4.80E-02

Q9ULY5, P20749, Q14643, P01375, Q13191, Q16539

CLEC4E, BCL3, ITPR1, TNF, CBLB, MAPK14

Tolvaptan

hsa04640

Hematopoietic cell lineage

1.71E-06

P13612, P14778, P27930, P11215, P15144, P11836, P25063, P07766, P09693, P01732, P01730, P09564, P13765, P01375

ITGA4, IL1R1, IL1R2, ITGAM, ANPEP, MS4A1, CD24, CD3E, CD3G, CD8A, CD4, CD7, HLA-DOB, TNF

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
P06239	LCK	Tyrosine-protein kinase Lck	P13612	ITGA4	Integrin alpha-4	0.732
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13612	ITGA4	Integrin alpha-4	-0.771
P06239	LCK	Tyrosine-protein kinase Lck	P14778	IL1R1	Interleukin-1 receptor type 1	-0.782
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
P06239	LCK	Tyrosine-protein kinase Lck	P27930	IL1R2	Interleukin-1 receptor type 2	-0.779
Q13547	HDAC1	Histone deacetylase 1	P27930	IL1R2	Interleukin-1 receptor type 2	-0.837
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P27930	IL1R2	Interleukin-1 receptor type 2	0.924
Q13547	HDAC1	Histone deacetylase 1	P11215	ITGAM	Integrin alpha-M	-0.751
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P15144	ANPEP	Aminopeptidase N	0.879
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P11836	MS4A1	B-lymphocyte antigen CD20	-0.705
P06239	LCK	Tyrosine-protein kinase Lck	P25063	CD24	Signal transducer CD24	-0.779
Q13547	HDAC1	Histone deacetylase 1	P25063	CD24	Signal transducer CD24	-0.706
P06239	LCK	Tyrosine-protein kinase Lck	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.928
Q13547	HDAC1	Histone deacetylase 1	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.802
P06239	LCK	Tyrosine-protein kinase Lck	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	0.752
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.815
P06239	LCK	Tyrosine-protein kinase Lck	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	0.841
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
P06239	LCK	Tyrosine-protein kinase Lck	P01730	CD4	T-cell surface glycoprotein CD4	0.746
P06239	LCK	Tyrosine-protein kinase Lck	P09564	CD7	T-cell antigen CD7	0.84
Q13547	HDAC1	Histone deacetylase 1	P09564	CD7	T-cell antigen CD7	0.738
P06239	LCK	Tyrosine-protein kinase Lck	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	0.777
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.73
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774

Tolvaptan

hsa04650

Natural killer cell mediated cytotoxicity

2.82E-07

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
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P78314	SH3BP2	SH3 domain-binding protein 2	0.809
P06239	LCK	Tyrosine-protein kinase Lck	P06239	LCK	Tyrosine-protein kinase Lck	1
Q13547	HDAC1	Histone deacetylase 1	P06239	LCK	Tyrosine-protein kinase Lck	0.811
P06239	LCK	Tyrosine-protein kinase Lck	O60880	SH2D1A	SH2 domain-containing protein 1A	0.906
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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	O60880	SH2D1A	SH2 domain-containing protein 1A	0.869
P06239	LCK	Tyrosine-protein kinase Lck	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.927
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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.74
Q13547	HDAC1	Histone deacetylase 1	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.774
P06239	LCK	Tyrosine-protein kinase Lck	Q13241	KLRD1	Natural killer cells antigen CD94	0.758
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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q13241	KLRD1	Natural killer cells antigen CD94	0.863
P06239	LCK	Tyrosine-protein kinase Lck	P26718	KLRK1	NKG2-D type II integral membrane protein	0.886
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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P26718	KLRK1	NKG2-D type II integral membrane protein	0.762
P06239	LCK	Tyrosine-protein kinase Lck	O14931	NCR3	Natural cytotoxicity triggering receptor 3	0.732
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
P06239	LCK	Tyrosine-protein kinase Lck	P26717	KLRC2	NKG2-C type II integral membrane protein	0.756
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P26717	KLRC2	NKG2-C type II integral membrane protein	-0.838
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P26717	KLRC2	NKG2-C type II integral membrane protein	0.853
P06239	LCK	Tyrosine-protein kinase Lck	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	0.756
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	-0.838
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	0.853

Tolvaptan

hsa04657

IL-17 signaling pathway

1.59E-05

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

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

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
P06737	PYGL	Glycogen phosphorylase, liver form	O00463	TRAF5	TNF receptor-associated factor 5	-0.924
P14780	MMP9	Matrix metalloproteinase-9	O00463	TRAF5	TNF receptor-associated factor 5	-0.917
Q16539	MAPK14	Mitogen-activated protein kinase 14	O00463	TRAF5	TNF receptor-associated factor 5	-0.837
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O00463	TRAF5	TNF receptor-associated factor 5	-0.875
P06737	PYGL	Glycogen phosphorylase, liver form	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.863
P14780	MMP9	Matrix metalloproteinase-9	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.778
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q16539	MAPK14	Mitogen-activated protein kinase 14	1
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.833
P06737	PYGL	Glycogen phosphorylase, liver form	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.815
P14780	MMP9	Matrix metalloproteinase-9	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.75
Q16539	MAPK14	Mitogen-activated protein kinase 14	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.78
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.781
P06737	PYGL	Glycogen phosphorylase, liver form	P09341	CXCL1	Growth-regulated alpha protein	0.74
P14780	MMP9	Matrix metalloproteinase-9	P09341	CXCL1	Growth-regulated alpha protein	0.771
Q16539	MAPK14	Mitogen-activated protein kinase 14	P09341	CXCL1	Growth-regulated alpha protein	0.7
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P09341	CXCL1	Growth-regulated alpha protein	0.781
P06737	PYGL	Glycogen phosphorylase, liver form	P14780	MMP9	Matrix metalloproteinase-9	0.917
P14780	MMP9	Matrix metalloproteinase-9	P14780	MMP9	Matrix metalloproteinase-9	1
Q16539	MAPK14	Mitogen-activated protein kinase 14	P14780	MMP9	Matrix metalloproteinase-9	0.778
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P14780	MMP9	Matrix metalloproteinase-9	0.942
P06737	PYGL	Glycogen phosphorylase, liver form	P80188	LCN2	Neutrophil gelatinase-associated lipocalin	0.706
P14780	MMP9	Matrix metalloproteinase-9	P80188	LCN2	Neutrophil gelatinase-associated lipocalin	0.888
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P80188	LCN2	Neutrophil gelatinase-associated lipocalin	0.721
P06737	PYGL	Glycogen phosphorylase, liver form	P01375	TNF	Tumor necrosis factor	0.759
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774

Tolvaptan

hsa04658

Th1 and Th2 cell differentiation

4.45E-16

Q04759, P07766, P20963, P09693, Q16539, P19174, P01730, P06239, Q14765, P42226, P23771, Q9UL17, P14784, P13765, Q13761

PRKCQ, CD3E, CD247, CD3G, MAPK14, PLCG1, CD4, LCK, STAT4, STAT6, GATA3, TBX21, IL2RB, HLA-DOB, RUNX3

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
P06737	PYGL	Glycogen phosphorylase, liver form	Q04759	PRKCQ	Protein kinase C theta type	-0.812
P14780	MMP9	Matrix metalloproteinase-9	Q04759	PRKCQ	Protein kinase C theta type	-0.787
P06239	LCK	Tyrosine-protein kinase Lck	Q04759	PRKCQ	Protein kinase C theta type	0.779
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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q04759	PRKCQ	Protein kinase C theta type	0.776
P06239	LCK	Tyrosine-protein kinase Lck	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.928
Q13547	HDAC1	Histone deacetylase 1	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.802
P06737	PYGL	Glycogen phosphorylase, liver form	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.728
P14780	MMP9	Matrix metalloproteinase-9	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.745
P06239	LCK	Tyrosine-protein kinase Lck	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.927
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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.74
P06737	PYGL	Glycogen phosphorylase, liver form	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.723
P14780	MMP9	Matrix metalloproteinase-9	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.719
P06239	LCK	Tyrosine-protein kinase Lck	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	0.752
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.815
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	0.744
P06737	PYGL	Glycogen phosphorylase, liver form	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.863
P14780	MMP9	Matrix metalloproteinase-9	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.778
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
P06239	LCK	Tyrosine-protein kinase Lck	P01730	CD4	T-cell surface glycoprotein CD4	0.746
P06239	LCK	Tyrosine-protein kinase Lck	P06239	LCK	Tyrosine-protein kinase Lck	1
Q13547	HDAC1	Histone deacetylase 1	P06239	LCK	Tyrosine-protein kinase Lck	0.811
P06737	PYGL	Glycogen phosphorylase, liver form	Q14765	STAT4	Signal transducer and activator of transcription 4	-0.736
P14780	MMP9	Matrix metalloproteinase-9	Q14765	STAT4	Signal transducer and activator of transcription 4	-0.861
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q14765	STAT4	Signal transducer and activator of transcription 4	-0.768
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q14765	STAT4	Signal transducer and activator of transcription 4	0.742
P06737	PYGL	Glycogen phosphorylase, liver form	P42226	STAT6	Signal transducer and activator of transcription 6	0.852
P06737	PYGL	Glycogen phosphorylase, liver form	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.753
P14780	MMP9	Matrix metalloproteinase-9	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.747
P06239	LCK	Tyrosine-protein kinase Lck	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	0.77
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.767
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	0.85
P06737	PYGL	Glycogen phosphorylase, liver form	Q9UL17	TBX21	T-box transcription factor TBX21	-0.738
P14780	MMP9	Matrix metalloproteinase-9	Q9UL17	TBX21	T-box transcription factor TBX21	-0.808
P06239	LCK	Tyrosine-protein kinase Lck	Q9UL17	TBX21	T-box transcription factor TBX21	0.866
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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q9UL17	TBX21	T-box transcription factor TBX21	0.735
P06239	LCK	Tyrosine-protein kinase Lck	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.727
Q13547	HDAC1	Histone deacetylase 1	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.816
P06737	PYGL	Glycogen phosphorylase, liver form	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.845
P14780	MMP9	Matrix metalloproteinase-9	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.714
P06239	LCK	Tyrosine-protein kinase Lck	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	0.777
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.73
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	0.795
P06239	LCK	Tyrosine-protein kinase Lck	Q13761	RUNX3	Runt-related transcription factor 3	0.85
Q13547	HDAC1	Histone deacetylase 1	Q13761	RUNX3	Runt-related transcription factor 3	0.884

Tolvaptan

hsa04659

Th17 cell differentiation

1.50E-11

P25963, Q04759, Q16539, P19174, P01730, P06239, P42224, P42226, P14784, P13765, P14778, Q9UL17, P23771, P84022, P08238, P07766, P09693, P20963

NFKBIA, PRKCQ, MAPK14, PLCG1, CD4, LCK, STAT1, STAT6, IL2RB, HLA-DOB, IL1R1, TBX21, GATA3, SMAD3, HSP90AB1, 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
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P25963	NFKBIA	NF-kappa-B inhibitor alpha	0.818
P06737	PYGL	Glycogen phosphorylase, liver form	Q04759	PRKCQ	Protein kinase C theta type	-0.812
P06239	LCK	Tyrosine-protein kinase Lck	Q04759	PRKCQ	Protein kinase C theta type	0.779
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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q04759	PRKCQ	Protein kinase C theta type	0.776
P06737	PYGL	Glycogen phosphorylase, liver form	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.863
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.833
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.869
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
P06239	LCK	Tyrosine-protein kinase Lck	P01730	CD4	T-cell surface glycoprotein CD4	0.746
P06239	LCK	Tyrosine-protein kinase Lck	P06239	LCK	Tyrosine-protein kinase Lck	1
Q13547	HDAC1	Histone deacetylase 1	P06239	LCK	Tyrosine-protein kinase Lck	0.811
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.783
P06737	PYGL	Glycogen phosphorylase, liver form	P42226	STAT6	Signal transducer and activator of transcription 6	0.852
P06239	LCK	Tyrosine-protein kinase Lck	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.727
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.717
Q13547	HDAC1	Histone deacetylase 1	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.816
P06737	PYGL	Glycogen phosphorylase, liver form	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.845
P06239	LCK	Tyrosine-protein kinase Lck	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	0.777
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.73
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	0.795
P06239	LCK	Tyrosine-protein kinase Lck	P14778	IL1R1	Interleukin-1 receptor type 1	-0.782
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
P06737	PYGL	Glycogen phosphorylase, liver form	Q9UL17	TBX21	T-box transcription factor TBX21	-0.738
P06239	LCK	Tyrosine-protein kinase Lck	Q9UL17	TBX21	T-box transcription factor TBX21	0.866
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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q9UL17	TBX21	T-box transcription factor TBX21	0.735
P06737	PYGL	Glycogen phosphorylase, liver form	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.753
P06239	LCK	Tyrosine-protein kinase Lck	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	0.77
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.767
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	0.85
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P84022	SMAD3	Mothers against decapentaplegic homolog 3	-0.77
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P08238	HSP90AB1	Heat shock protein HSP 90-beta	1
P06239	LCK	Tyrosine-protein kinase Lck	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.928
Q13547	HDAC1	Histone deacetylase 1	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.802
P06737	PYGL	Glycogen phosphorylase, liver form	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.723
P06239	LCK	Tyrosine-protein kinase Lck	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	0.752
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.815
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	0.744
P06737	PYGL	Glycogen phosphorylase, liver form	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.728
P06239	LCK	Tyrosine-protein kinase Lck	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.927
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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.74

Tolvaptan

hsa04660

T cell receptor signaling pathway

1.23E-11

P01375, Q9UDY8, Q04759, P42338, P10747, O95267, Q08881, P19174, P07766, P20963, P09693, P01730, P01732, Q13191, P06239, Q16539, P49841

TNF, MALT1, PRKCQ, PIK3CB, CD28, RASGRP1, ITK, PLCG1, CD3E, CD247, CD3G, CD4, 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
P06737	PYGL	Glycogen phosphorylase, liver form	P01375	TNF	Tumor necrosis factor	0.759
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774
P14780	MMP9	Matrix metalloproteinase-9	Q9UDY8	MALT1	Mucosa-associated lymphoid tissue lymphoma translocation protein 1	-0.767
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q9UDY8	MALT1	Mucosa-associated lymphoid tissue lymphoma translocation protein 1	0.723
P06737	PYGL	Glycogen phosphorylase, liver form	Q04759	PRKCQ	Protein kinase C theta type	-0.812
P14780	MMP9	Matrix metalloproteinase-9	Q04759	PRKCQ	Protein kinase C theta type	-0.787
P06239	LCK	Tyrosine-protein kinase Lck	Q04759	PRKCQ	Protein kinase C theta type	0.779
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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q04759	PRKCQ	Protein kinase C theta type	0.776
Q13547	HDAC1	Histone deacetylase 1	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.774
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P10747	CD28	T-cell-specific surface glycoprotein CD28	0.794
P06737	PYGL	Glycogen phosphorylase, liver form	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.73
P14780	MMP9	Matrix metalloproteinase-9	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.792
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.806
P06737	PYGL	Glycogen phosphorylase, liver form	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.8
P14780	MMP9	Matrix metalloproteinase-9	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.855
P06239	LCK	Tyrosine-protein kinase Lck	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	0.774
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.812
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	0.746
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
P06239	LCK	Tyrosine-protein kinase Lck	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.928
Q13547	HDAC1	Histone deacetylase 1	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.802
P06737	PYGL	Glycogen phosphorylase, liver form	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.728
P14780	MMP9	Matrix metalloproteinase-9	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.745
P06239	LCK	Tyrosine-protein kinase Lck	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.927
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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.74
P06737	PYGL	Glycogen phosphorylase, liver form	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.723
P14780	MMP9	Matrix metalloproteinase-9	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.719
P06239	LCK	Tyrosine-protein kinase Lck	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	0.752
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.815
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	0.744
P06239	LCK	Tyrosine-protein kinase Lck	P01730	CD4	T-cell surface glycoprotein CD4	0.746
P06737	PYGL	Glycogen phosphorylase, liver form	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.72
P14780	MMP9	Matrix metalloproteinase-9	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.742
P06239	LCK	Tyrosine-protein kinase Lck	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	0.841
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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	0.92
P14780	MMP9	Matrix metalloproteinase-9	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	-0.793
P06239	LCK	Tyrosine-protein kinase Lck	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	0.714
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
P06239	LCK	Tyrosine-protein kinase Lck	P06239	LCK	Tyrosine-protein kinase Lck	1
Q13547	HDAC1	Histone deacetylase 1	P06239	LCK	Tyrosine-protein kinase Lck	0.811
P06737	PYGL	Glycogen phosphorylase, liver form	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.863
P14780	MMP9	Matrix metalloproteinase-9	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.778
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.833
P06737	PYGL	Glycogen phosphorylase, liver form	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.815
P14780	MMP9	Matrix metalloproteinase-9	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.75
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.781

Tolvaptan

hsa04664

Fc epsilon RI signaling pathway

6.97E-03

P04141, P07948, P19174, P09917

CSF2, LYN, PLCG1, ALOX5

Tolvaptan

hsa04668

TNF signaling pathway

4.74E-02

Q99941, P01584, O95429

CREBL1, IL1B, BAG4

Tolvaptan

hsa04710

Circadian rhythm

2.43E-02

O15516

CLOCK

Tolvaptan

hsa04713

Circadian entrainment

2.18E-02

P0DP23, P62873, P63218, P50151

CALM1, GNB1, GNG5, GNG10

Tolvaptan

hsa04714

Thermogenesis

6.01E-04

Q16539, P51828, P62753, P33121, P12074, O15239, Q16718, O14521

MAPK14, ADCY7, RPS6, ACSL1, COX6A1, NDUFA1, NDUFA5, SDHD

Tolvaptan

hsa04723

Retrograde endocannabinoid signaling

2.68E-02

P48169, P62873

GABRA4, GNB1

Tolvaptan

hsa04724

Glutamatergic synapse

1.57E-02

P62873, P63218, P50151, P15104

GNB1, GNG5, GNG10, GLUL

Tolvaptan

hsa04725

Cholinergic synapse

2.17E-02

P51828, P18848, Q13557

ADCY7, ATF4, CAMK2D

Tolvaptan

hsa04726

Serotonergic synapse

3.80E-02

P62873, P63218, P50151, P09917

GNB1, GNG5, GNG10, ALOX5

Tolvaptan

hsa04727

GABAergic synapse

1.40E-03

P62873, P63218, P50151, P48169, P15104

GNB1, GNG5, GNG10, GABRA4, GLUL

Tolvaptan

hsa04728

Dopaminergic synapse

4.78E-02

Q99941, P18848, Q13557

CREBL1, ATF4, CAMK2D

Tolvaptan

hsa04730

Long-term depression

4.86E-02

Q14344, P07948

GNA13, LYN

Tolvaptan

hsa04742

Taste transduction

4.80E-02

P48169

GABRA4

Tolvaptan

hsa04744

Phototransduction

9.21E-03

P62873, P0DP23

GNB1, CALM1

Tolvaptan

hsa04750

Inflammatory mediator regulation of TRP channels

7.62E-04

P14778, P01584, P51828, Q13557, P19174, P42338, P24723, Q04759

IL1R1, IL1B, ADCY7, CAMK2D, PLCG1, PIK3CB, PRKCH, PRKCQ

Tolvaptan

hsa04911

Insulin secretion

2.03E-05

P51828, Q99941, P18848, Q13557

ADCY7, CREBL1, ATF4, CAMK2D

Tolvaptan

hsa04912

GnRH signaling pathway

9.00E-03

P51828, P18848, Q13557, Q16539, Q9Y6R4, Q14643, P22694

ADCY7, ATF4, CAMK2D, MAPK14, MAP3K4, ITPR1, PRKACB

Tolvaptan

hsa04915

Estrogen signaling pathway

5.03E-04

Q99941, P18848, P51828, P07900, P11142

CREBL1, ATF4, ADCY7, HSP90AA1, HSPA8

Tolvaptan

hsa04918

Thyroid hormone synthesis

1.69E-03

P51828, Q99941, P18848, P02768

ADCY7, CREBL1, ATF4, ALB

Tolvaptan

hsa04920

Adipocytokine signaling pathway

4.72E-02

P33121, Q04759, Q9Y4H2, P01375

ACSL1, PRKCQ, IRS2, TNF

Tolvaptan

hsa04922

Glucagon signaling pathway

4.23E-02

P22694, P06737, Q12778, Q14643

PRKACB, PYGL, FOXO1, ITPR1

Tolvaptan

hsa04923

Regulation of lipolysis in adipocytes

2.24E-02

P07550, P42338, Q9Y4H2

ADRB2, PIK3CB, IRS2

Tolvaptan

hsa04924

Renin secretion

1.04E-02

P22694, P07550, Q14643

PRKACB, ADRB2, ITPR1

Tolvaptan

hsa04925

Aldosterone synthesis and secretion

2.51E-05

Q99941, P18848, P51828, Q13557, P23634

CREBL1, ATF4, ADCY7, CAMK2D, ATP2B4

Tolvaptan

hsa04926

Relaxin signaling pathway

3.34E-02

Q99941, P18848, P51828

CREBL1, ATF4, ADCY7

Tolvaptan

hsa04927

Cortisol synthesis and secretion

4.16E-03

Q99941, P18848, P51828

CREBL1, ATF4, ADCY7

Tolvaptan

hsa04928

Parathyroid hormone synthesis, secretion and action

3.09E-03

Q14643, P51828, P22694, P23771, Q99941, P18848, P10415

ITPR1, ADCY7, PRKACB, GATA3, CREBL1, ATF4, BCL2

Tolvaptan

hsa04932

Non-alcoholic fatty liver disease

3.62E-02

P49841, Q16718, O14521

GSK3B, NDUFA5, SDHD

Tolvaptan

hsa04934

Cushing syndrome

1.09E-05

Q99941, P18848, P51828, O15169, Q13557

CREBL1, ATF4, ADCY7, AXIN1, CAMK2D

Tolvaptan

hsa04935

Growth hormone synthesis, secretion and action

2.72E-02

P51828, Q99941, P18848

ADCY7, CREBL1, ATF4

Tolvaptan

hsa04964

Proximal tubule bicarbonate reclamation

4.48E-02

P00918

CA2

Tolvaptan

hsa04966

Collecting duct acid secretion

4.48E-02

P00918

CA2

Tolvaptan

hsa04971

Gastric acid secretion

1.48E-02

P51828, P15311, Q13557

ADCY7, VIL2, CAMK2D

Tolvaptan

hsa04973

Carbohydrate digestion and absorption

1.29E-02

O43451, P42338

MGAM, PIK3CB

Tolvaptan

hsa04975

Fat digestion and absorption

2.80E-02

O14494

PLPP1

Tolvaptan

hsa04976

Bile secretion

3.32E-02

O43315, P08183

AQP9, ABCB1

Tolvaptan

hsa05010

Alzheimer disease

2.07E-02

Q92542, P05496, P12074, O75460, P01584, O15169, P45880

NCSTN, ATP5G1, COX6A1, ERN1, IL1B, AXIN1, VDAC2

Tolvaptan

hsa05012

Parkinson disease

1.77E-02

P60604, P19174, P0DP23, Q71U36, Q13509, P68371

UBE2G2, PLCG1, CALM1, TUBA1A, TUBB3, TUBB2C

Tolvaptan

hsa05020

Prion disease

1.37E-03

P01584, P46531, P11142, Q16718, O14521, P05496, P12074, P45880, P49841, Q99941, Q16539

IL1B, NOTCH1, HSPA8, NDUFA5, SDHD, ATP5G1, COX6A1, VDAC2, GSK3B, CREBL1, MAPK14

Tolvaptan

hsa05022

Pathways of neurodegeneration - multiple diseases

1.24E-02

P49841, Q16718, O14521, Q13561, Q16539, Q08752

GSK3B, NDUFA5, SDHD, DCTN2, MAPK14, PPID

Tolvaptan

hsa05030

Cocaine addiction

4.87E-02

Q99941, P18848

CREBL1, ATF4

Tolvaptan

hsa05031

Amphetamine addiction

6.41E-03

Q13557, Q99941, P18848

CAMK2D, CREBL1, ATF4

Tolvaptan

hsa05032

Morphine addiction

1.06E-03

P62873, P63218, P50151, Q13370, P48169

GNB1, GNG5, GNG10, PDE3B, GABRA4

Tolvaptan

hsa05033

Nicotine addiction

2.43E-02

P48169

GABRA4

Tolvaptan

hsa05034

Alcoholism

2.89E-03

Q93077, P62807, O60814, P68431

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

Tolvaptan

hsa05120

Epithelial cell signaling in Helicobacter pylori infection

6.09E-06

Q16539, P25963, Q13488, P09341, P19875, P19174, P25024, P25025, P07948

MAPK14, NFKBIA, TCIRG1, CXCL1, CXCL2, PLCG1, CXCR1, CXCR2, LYN

Tolvaptan

hsa05130

Pathogenic Escherichia coli infection

3.19E-02

Q71U36, P16333, Q13509, P68371, Q14344, P25963

TUBA1A, NCK1, TUBB3, TUBB2C, GNA13, NFKBIA

Tolvaptan

hsa05132

Salmonella infection

1.44E-03

P25963, P08238, Q13546, Q13489, O75369, O60282, Q71U36, Q13509, P68371, P49754

NFKBIA, HSP90AB1, RIPK1, BIRC3, FLNB, KIF5C, TUBA1A, TUBB3, TUBB2C, VPS41

Tolvaptan

hsa05133

Pertussis

2.35E-03

P0DP23, P0C0L4

CALM1, C4A

Tolvaptan

hsa05134

Legionellosis

1.49E-03

P25963, P11215, P11142, P09341, P19875

NFKBIA, ITGAM, HSPA8, CXCL1, CXCL2

Tolvaptan

hsa05140

Leishmaniasis

1.41E-06

P13612, O75015, P14598, P11215, P42224, P13765, O60603, P25963, P01375, P49006, Q16539, Q15080

ITGA4, FCGR3B, NCF1, ITGAM, STAT1, HLA-DOB, TLR2, NFKBIA, TNF, MARCKSL1, MAPK14, NCF4

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
P14780	MMP9	Matrix metalloproteinase-9	P13612	ITGA4	Integrin alpha-4	-0.7
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13612	ITGA4	Integrin alpha-4	-0.771
P14780	MMP9	Matrix metalloproteinase-9	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.928
Q16539	MAPK14	Mitogen-activated protein kinase 14	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.814
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.893
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P14598	NCF1	Neutrophil cytosol factor 1	0.785
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P11215	ITGAM	Integrin alpha-M	-0.78
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.783
P14780	MMP9	Matrix metalloproteinase-9	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.714
Q16539	MAPK14	Mitogen-activated protein kinase 14	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.754
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.73
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.756
P14780	MMP9	Matrix metalloproteinase-9	O60603	TLR2	Toll-like receptor 2	0.89
Q16539	MAPK14	Mitogen-activated protein kinase 14	O60603	TLR2	Toll-like receptor 2	0.73
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O60603	TLR2	Toll-like receptor 2	0.867
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P25963	NFKBIA	NF-kappa-B inhibitor alpha	0.818
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774
Q16539	MAPK14	Mitogen-activated protein kinase 14	P49006	MARCKSL1	MARCKS-related protein	-0.852
P14780	MMP9	Matrix metalloproteinase-9	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.778
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q16539	MAPK14	Mitogen-activated protein kinase 14	1
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.833
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.708
P14780	MMP9	Matrix metalloproteinase-9	Q15080	NCF4	Neutrophil cytosol factor 4	0.869
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q15080	NCF4	Neutrophil cytosol factor 4	0.764
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	Q15080	NCF4	Neutrophil cytosol factor 4	0.719

Tolvaptan

hsa05143

African trypanosomiasis

4.81E-02

P69905, P68871

HBA2, HBB

Tolvaptan

hsa05144

Malaria

1.54E-02

P60033, O60603, P01375, P35443, P26718

CD81, TLR2, TNF, THBS4, KLRK1

Tolvaptan

hsa05145

Toxoplasmosis

1.28E-02

Q16539, P10415, Q13489, P13765

MAPK14, BCL2, BIRC3, HLA-DOB

Tolvaptan

hsa05146

Amoebiasis

1.21E-08

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

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

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
P14780	MMP9	Matrix metalloproteinase-9	P09341	CXCL1	Growth-regulated alpha protein	0.771
Q16539	MAPK14	Mitogen-activated protein kinase 14	P09341	CXCL1	Growth-regulated alpha protein	0.7
P06239	LCK	Tyrosine-protein kinase Lck	P09341	CXCL1	Growth-regulated alpha protein	-0.805
Q13547	HDAC1	Histone deacetylase 1	P09341	CXCL1	Growth-regulated alpha protein	-0.736
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P09341	CXCL1	Growth-regulated alpha protein	0.781
Q13547	HDAC1	Histone deacetylase 1	P19875	CXCL2	C-X-C motif chemokine 2	-0.862
Q16539	MAPK14	Mitogen-activated protein kinase 14	P14778	IL1R1	Interleukin-1 receptor type 1	0.76
P06239	LCK	Tyrosine-protein kinase Lck	P14778	IL1R1	Interleukin-1 receptor type 1	-0.782
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
P14780	MMP9	Matrix metalloproteinase-9	P27930	IL1R2	Interleukin-1 receptor type 2	0.851
Q16539	MAPK14	Mitogen-activated protein kinase 14	P27930	IL1R2	Interleukin-1 receptor type 2	0.811
P06239	LCK	Tyrosine-protein kinase Lck	P27930	IL1R2	Interleukin-1 receptor type 2	-0.779
Q13547	HDAC1	Histone deacetylase 1	P27930	IL1R2	Interleukin-1 receptor type 2	-0.837
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P27930	IL1R2	Interleukin-1 receptor type 2	0.924
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774
P14780	MMP9	Matrix metalloproteinase-9	O60603	TLR2	Toll-like receptor 2	0.89
Q16539	MAPK14	Mitogen-activated protein kinase 14	O60603	TLR2	Toll-like receptor 2	0.73
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O60603	TLR2	Toll-like receptor 2	0.867
Q13547	HDAC1	Histone deacetylase 1	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.774
Q13547	HDAC1	Histone deacetylase 1	P11215	ITGAM	Integrin alpha-M	-0.751
P14780	MMP9	Matrix metalloproteinase-9	P05089	ARG1	Arginase-1	0.881
Q16539	MAPK14	Mitogen-activated protein kinase 14	P05089	ARG1	Arginase-1	0.702
P06239	LCK	Tyrosine-protein kinase Lck	P05089	ARG1	Arginase-1	-0.803
Q13547	HDAC1	Histone deacetylase 1	P05089	ARG1	Arginase-1	-0.769
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P05089	ARG1	Arginase-1	0.811
P14780	MMP9	Matrix metalloproteinase-9	P22694	PRKACB	cAMP-dependent protein kinase catalytic subunit beta	-0.826
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P22694	PRKACB	cAMP-dependent protein kinase catalytic subunit beta	-0.779
P06239	LCK	Tyrosine-protein kinase Lck	P12814	ACTN1	Alpha-actinin-1	-0.867
Q13547	HDAC1	Histone deacetylase 1	P12814	ACTN1	Alpha-actinin-1	-0.887
P14780	MMP9	Matrix metalloproteinase-9	P08311	CTSG	Cathepsin G	0.79
P06239	LCK	Tyrosine-protein kinase Lck	P08311	CTSG	Cathepsin G	-0.816
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P08311	CTSG	Cathepsin G	0.709

Tolvaptan

hsa05150

Staphylococcus aureus infection

5.34E-03

P0C0L4, P21730, P21462, O75015, P13765, Q16581, P13646, P12838

C4A, C5AR1, FPR1, FCGR3B, HLA-DOB, C3AR1, KRT13, DEFA4

Tolvaptan

hsa05152

Tuberculosis

1.81E-02

P48382, P10415, P13765, Q16539

RFX5, BCL2, HLA-DOB, MAPK14

Tolvaptan

hsa05160

Hepatitis C

4.55E-02

O00501, P29728, P01106

CLDN5, OAS2, MYC

Tolvaptan

hsa05161

Hepatitis B

3.34E-02

Q99941, P18848, P27348

CREBL1, ATF4, YWHAQ

Tolvaptan

hsa05163

Human cytomegalovirus infection

3.87E-04

P25963, P62873, P63218, P50151, Q14643, P0DP23, Q14344, P49841, P14778, P25025, Q16539, P04637, O00463, P30101, P01568

NFKBIA, GNB1, GNG5, GNG10, ITPR1, CALM1, GNA13, GSK3B, IL1R1, CXCR2, MAPK14, TP53, TRAF5, PDIA3, IFNA21

Tolvaptan

hsa05167

Kaposi sarcoma-associated herpesvirus infection

8.62E-05

P01568, P42224, P25963, P62873, P63218, P50151, P19174, P07948, P04141, P0DP23

IFNA21, STAT1, NFKBIA, GNB1, GNG5, GNG10, PLCG1, LYN, CSF2, CALM1

Tolvaptan

hsa05168

Herpes simplex virus 1 infection

3.79E-02

P25963, P01568, P42224, Q07955, Q01130, Q13243, P30101, Q13398, O75820

NFKBIA, IFNA21, STAT1, SFRS1, SFRS2, SFRS5, PDIA3, ZNF211, ZNF189

Tolvaptan

hsa05169

Epstein-Barr virus infection

1.02E-03

P13765, P01106, Q13547, O00463, P16070, P10415, Q16539, P07948, Q13761, P24522, Q8WV28, P01375, O60603, P07766, P09693, P20963

HLA-DOB, MYC, HDAC1, TRAF5, CD44, BCL2, MAPK14, LYN, RUNX3, GADD45A, BLNK, TNF, TLR2, 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
P06737	PYGL	Glycogen phosphorylase, liver form	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.845
P06239	LCK	Tyrosine-protein kinase Lck	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	0.777
P06239	LCK	Tyrosine-protein kinase Lck	P01106	MYC	Myc proto-oncogene protein	0.719
P06239	LCK	Tyrosine-protein kinase Lck	Q13547	HDAC1	Histone deacetylase 1	0.811
P06737	PYGL	Glycogen phosphorylase, liver form	O00463	TRAF5	TNF receptor-associated factor 5	-0.924
P06239	LCK	Tyrosine-protein kinase Lck	O00463	TRAF5	TNF receptor-associated factor 5	0.718
P06737	PYGL	Glycogen phosphorylase, liver form	P16070	CD44	CD44 antigen	0.803
P06737	PYGL	Glycogen phosphorylase, liver form	P10415	BCL2	Apoptosis regulator Bcl-2	-0.766
P06737	PYGL	Glycogen phosphorylase, liver form	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.863
P06239	LCK	Tyrosine-protein kinase Lck	P07948	LYN	Tyrosine-protein kinase Lyn	-0.701
P06239	LCK	Tyrosine-protein kinase Lck	Q13761	RUNX3	Runt-related transcription factor 3	0.85
P06737	PYGL	Glycogen phosphorylase, liver form	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.822
P06239	LCK	Tyrosine-protein kinase Lck	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	-0.724
P06737	PYGL	Glycogen phosphorylase, liver form	Q8WV28	BLNK	B-cell linker protein	-0.706
P06737	PYGL	Glycogen phosphorylase, liver form	P01375	TNF	Tumor necrosis factor	0.759
P06737	PYGL	Glycogen phosphorylase, liver form	O60603	TLR2	Toll-like receptor 2	0.836
P06239	LCK	Tyrosine-protein kinase Lck	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.928
P06737	PYGL	Glycogen phosphorylase, liver form	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.723
P06239	LCK	Tyrosine-protein kinase Lck	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	0.752
P06737	PYGL	Glycogen phosphorylase, liver form	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.728
P06239	LCK	Tyrosine-protein kinase Lck	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.927

Tolvaptan

hsa05170

Human immunodeficiency virus 1 infection

1.19E-02

P62873, P63218, P50151, P0DP23, P30101, P01568, P25963, P19174

GNB1, GNG5, GNG10, CALM1, PDIA3, IFNA21, NFKBIA, PLCG1

Tolvaptan

hsa05200

Pathways in cancer

1.99E-03

P08238, P42224, P25963, P19174, P43246, P84022, P20585, P62873, P63218, P50151, Q14344, O75293, P0DP23, P01568, P14784

HSP90AB1, STAT1, NFKBIA, PLCG1, MSH2, SMAD3, MSH3, GNB1, GNG5, GNG10, GNA13, GADD45B, CALM1, IFNA21, IL2RB

Tolvaptan

hsa05202

Transcriptional misregulation in cancer

1.15E-08

Q12778, Q15532, Q13315, P41732, P14780, P27930, Q15744, Q16548, Q13489, Q13077, Q15652, O15550, P35226, P05164, P12838, P08246, Q9C0K0, P41182, P68431, Q13547, Q92769, P12980, P24522

FOXO1, SS18, ATM, TSPAN7, MMP9, IL1R2, CEBPE, BCL2A1, BIRC3, TRAF1, JMJD1C, UTX, BMI1, MPO, DEFA4, ELA2, BCL11B, BCL6, H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12, 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
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q12778	FOXO1	Forkhead box protein O1	0.795
P06737	PYGL	Glycogen phosphorylase, liver form	Q15532	SS18	Protein SSXT	-0.772
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	Q15532	SS18	Protein SSXT	-0.829
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q13315	ATM	Serine-protein kinase ATM	0.723
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P41732	TSPAN7	Tetraspanin-7	0.703
P06737	PYGL	Glycogen phosphorylase, liver form	P14780	MMP9	Matrix metalloproteinase-9	0.917
P14780	MMP9	Matrix metalloproteinase-9	P14780	MMP9	Matrix metalloproteinase-9	1
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P14780	MMP9	Matrix metalloproteinase-9	0.942
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P14780	MMP9	Matrix metalloproteinase-9	-0.746
P06737	PYGL	Glycogen phosphorylase, liver form	P27930	IL1R2	Interleukin-1 receptor type 2	0.881
P14780	MMP9	Matrix metalloproteinase-9	P27930	IL1R2	Interleukin-1 receptor type 2	0.851
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P27930	IL1R2	Interleukin-1 receptor type 2	0.924
P14780	MMP9	Matrix metalloproteinase-9	Q15744	CEBPE	CCAAT/enhancer-binding protein epsilon	0.7
P06737	PYGL	Glycogen phosphorylase, liver form	Q16548	BCL2A1	Bcl-2-related protein A1	0.967
P14780	MMP9	Matrix metalloproteinase-9	Q16548	BCL2A1	Bcl-2-related protein A1	0.921
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q16548	BCL2A1	Bcl-2-related protein A1	0.913
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	Q16548	BCL2A1	Bcl-2-related protein A1	0.751
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q16548	BCL2A1	Bcl-2-related protein A1	-0.701
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.832
P06737	PYGL	Glycogen phosphorylase, liver form	Q13077	TRAF1	TNF receptor-associated factor 1	-0.783
P14780	MMP9	Matrix metalloproteinase-9	Q13077	TRAF1	TNF receptor-associated factor 1	-0.758
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q13077	TRAF1	TNF receptor-associated factor 1	-0.712
P06737	PYGL	Glycogen phosphorylase, liver form	Q15652	JMJD1C	Probable JmjC domain-containing histone demethylation protein 2C	0.754
P06737	PYGL	Glycogen phosphorylase, liver form	O15550	UTX	Lysine-specific demethylase 6A	0.724
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	O15550	UTX	Lysine-specific demethylase 6A	0.73
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	O15550	UTX	Lysine-specific demethylase 6A	-0.778
P06737	PYGL	Glycogen phosphorylase, liver form	P35226	BMI1	Polycomb complex protein BMI-1	-0.73
P14780	MMP9	Matrix metalloproteinase-9	P35226	BMI1	Polycomb complex protein BMI-1	-0.89
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P35226	BMI1	Polycomb complex protein BMI-1	-0.778
P06737	PYGL	Glycogen phosphorylase, liver form	P35226	BMI1	Polycomb complex protein BMI-1	-0.73
P14780	MMP9	Matrix metalloproteinase-9	P35226	BMI1	Polycomb complex protein BMI-1	-0.89
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P35226	BMI1	Polycomb complex protein BMI-1	-0.778
P06737	PYGL	Glycogen phosphorylase, liver form	P05164	MPO	Myeloperoxidase	0.858
P14780	MMP9	Matrix metalloproteinase-9	P05164	MPO	Myeloperoxidase	0.812
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P05164	MPO	Myeloperoxidase	0.711
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	P05164	MPO	Myeloperoxidase	0.711
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P05164	MPO	Myeloperoxidase	-0.866
P06737	PYGL	Glycogen phosphorylase, liver form	P12838	DEFA4	Neutrophil defensin 4	0.7
P14780	MMP9	Matrix metalloproteinase-9	P12838	DEFA4	Neutrophil defensin 4	0.858
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P12838	DEFA4	Neutrophil defensin 4	0.767
P06737	PYGL	Glycogen phosphorylase, liver form	P08246	ELA2	Neutrophil elastase	0.817
P14780	MMP9	Matrix metalloproteinase-9	P08246	ELA2	Neutrophil elastase	0.859
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P08246	ELA2	Neutrophil elastase	0.703
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P08246	ELA2	Neutrophil elastase	-0.76
P06737	PYGL	Glycogen phosphorylase, liver form	Q9C0K0	BCL11B	B-cell lymphoma/leukemia 11B	-0.742
P14780	MMP9	Matrix metalloproteinase-9	Q9C0K0	BCL11B	B-cell lymphoma/leukemia 11B	-0.752
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q9C0K0	BCL11B	B-cell lymphoma/leukemia 11B	-0.765
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q9C0K0	BCL11B	B-cell lymphoma/leukemia 11B	0.879
P06737	PYGL	Glycogen phosphorylase, liver form	P41182	BCL6	B-cell lymphoma 6 protein	0.847
P14780	MMP9	Matrix metalloproteinase-9	P41182	BCL6	B-cell lymphoma 6 protein	0.812
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P41182	BCL6	B-cell lymphoma 6 protein	0.9
Q16581	C3AR1	C3a anaphylatoxin chemotactic receptor	P68431	H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12	Histone H3.1	-0.79
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
P14780	MMP9	Matrix metalloproteinase-9	P12980	LYL1	Protein lyl-1	0.716
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P12980	LYL1	Protein lyl-1	0.782
P06737	PYGL	Glycogen phosphorylase, liver form	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.822
P14780	MMP9	Matrix metalloproteinase-9	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.765
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.801
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	-0.734

Tolvaptan

hsa05203

Viral carcinogenesis

2.63E-03

Q99941, P18848, P27348, Q15283, P61978, P62807, O60814

CREBL1, ATF4, YWHAQ, RASA2, HNRPK, HIST1H2BC, H2BC12

Tolvaptan

hsa05204

Chemical carcinogenesis

1.48E-02

P78417, P11712

GSTO1, CYP2C9

Tolvaptan

hsa05206

MicroRNAs in cancer

2.97E-03

P15311, P21860, P61978, P46531, P63279, P22105

VIL2, ERBB3, HNRPK, NOTCH1, UBE2I, TNXB

Tolvaptan

hsa05212

Pancreatic cancer

1.05E-02

P42224, P37173, P84022, O75293

STAT1, TGFBR2, SMAD3, GADD45B

Tolvaptan

hsa05214

Glioma

4.75E-02

P0DP23, P19174, O75293

CALM1, PLCG1, GADD45B

Tolvaptan

hsa05217

Basal cell carcinoma

1.43E-02

Q13635, P49841, Q9UJU2, P24522

PTCH1, GSK3B, LEF1, GADD45A

Tolvaptan

hsa05219

Bladder cancer

4.07E-02

P14780, P04637

MMP9, TP53

Tolvaptan

hsa05224

Breast cancer

4.75E-02

P49841, Q92837, P04637, P24522

GSK3B, FRAT1, TP53, GADD45A

Tolvaptan

hsa05235

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

3.39E-06

P42338, O95267, P19174, P07766, P20963, P09693, P06239, O60603, P10747, Q04759, Q16539, P01730

PIK3CB, RASGRP1, PLCG1, CD3E, CD247, CD3G, LCK, TLR2, CD28, PRKCQ, MAPK14, CD4

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	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.774
Q16539	MAPK14	Mitogen-activated protein kinase 14	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.716
Q13547	HDAC1	Histone deacetylase 1	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.7
P06239	LCK	Tyrosine-protein kinase Lck	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.928
Q13547	HDAC1	Histone deacetylase 1	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.802
P06239	LCK	Tyrosine-protein kinase Lck	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.927
Q13547	HDAC1	Histone deacetylase 1	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.87
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.74
Q16539	MAPK14	Mitogen-activated protein kinase 14	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.744
P06239	LCK	Tyrosine-protein kinase Lck	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	0.752
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	0.744
P06239	LCK	Tyrosine-protein kinase Lck	P06239	LCK	Tyrosine-protein kinase Lck	1
Q13547	HDAC1	Histone deacetylase 1	P06239	LCK	Tyrosine-protein kinase Lck	0.811
Q16539	MAPK14	Mitogen-activated protein kinase 14	O60603	TLR2	Toll-like receptor 2	0.73
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	O60603	TLR2	Toll-like receptor 2	-0.717
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P10747	CD28	T-cell-specific surface glycoprotein CD28	0.794
P06239	LCK	Tyrosine-protein kinase Lck	Q04759	PRKCQ	Protein kinase C theta type	0.779
Q13547	HDAC1	Histone deacetylase 1	Q04759	PRKCQ	Protein kinase C theta type	0.723
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q04759	PRKCQ	Protein kinase C theta type	0.776
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q16539	MAPK14	Mitogen-activated protein kinase 14	1
Q16539	MAPK14	Mitogen-activated protein kinase 14	P01730	CD4	T-cell surface glycoprotein CD4	-0.707
P06239	LCK	Tyrosine-protein kinase Lck	P01730	CD4	T-cell surface glycoprotein CD4	0.746

Tolvaptan

hsa05310

Asthma

2.81E-02

P13765, P12724, P01375

HLA-DOB, RNASE3, TNF

Tolvaptan

hsa05321

Inflammatory bowel disease

2.46E-10

O60603, P01375, P13765, Q14765, Q9UL17, P42226, P23771

TLR2, TNF, HLA-DOB, STAT4, TBX21, STAT6, GATA3

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
P06737	PYGL	Glycogen phosphorylase, liver form	O60603	TLR2	Toll-like receptor 2	0.836
P14780	MMP9	Matrix metalloproteinase-9	O60603	TLR2	Toll-like receptor 2	0.89
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	O60603	TLR2	Toll-like receptor 2	0.867
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	O60603	TLR2	Toll-like receptor 2	-0.717
P06737	PYGL	Glycogen phosphorylase, liver form	P01375	TNF	Tumor necrosis factor	0.759
P14780	MMP9	Matrix metalloproteinase-9	P01375	TNF	Tumor necrosis factor	0.897
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P01375	TNF	Tumor necrosis factor	0.774
P06737	PYGL	Glycogen phosphorylase, liver form	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.845
P14780	MMP9	Matrix metalloproteinase-9	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.714
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.73
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	0.795
P06737	PYGL	Glycogen phosphorylase, liver form	Q14765	STAT4	Signal transducer and activator of transcription 4	-0.736
P14780	MMP9	Matrix metalloproteinase-9	Q14765	STAT4	Signal transducer and activator of transcription 4	-0.861
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q14765	STAT4	Signal transducer and activator of transcription 4	-0.768
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q14765	STAT4	Signal transducer and activator of transcription 4	0.742
P06737	PYGL	Glycogen phosphorylase, liver form	Q9UL17	TBX21	T-box transcription factor TBX21	-0.738
P14780	MMP9	Matrix metalloproteinase-9	Q9UL17	TBX21	T-box transcription factor TBX21	-0.808
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	Q9UL17	TBX21	T-box transcription factor TBX21	-0.861
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	Q9UL17	TBX21	T-box transcription factor TBX21	0.735
P06737	PYGL	Glycogen phosphorylase, liver form	P42226	STAT6	Signal transducer and activator of transcription 6	0.852
P06737	PYGL	Glycogen phosphorylase, liver form	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.753
P14780	MMP9	Matrix metalloproteinase-9	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.747
P21730	C5AR1	C5a anaphylatoxin chemotactic receptor 1	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.767
P42330	AKR1C3	Aldo-keto reductase family 1 member C3	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	0.85

Tolvaptan

hsa05322

Systemic lupus erythematosus

1.31E-04

P09871, Q93077, P62807, O60814, P68431

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

Tolvaptan

hsa05323

Rheumatoid arthritis

1.60E-02

P13765, P10747, P09341, O60603

HLA-DOB, CD28, CXCL1, TLR2

Tolvaptan

hsa05332

Graft-versus-host disease

3.09E-06

P13765, P10747, P01375, P26715, Q13241

HLA-DOB, CD28, TNF, KLRC1, KLRD1

Tolvaptan

hsa05340

Primary immunodeficiency

2.19E-02

P01730, P01732, P07766, P06239

CD4, CD8A, CD3E, LCK

Tolvaptan

hsa05412

Arrhythmogenic right ventricular cardiomyopathy

4.48E-02

P54284

CACNB3

Tolvaptan

hsa05414

Dilated cardiomyopathy

2.60E-03

P54284, P09493, P26678

CACNB3, TPM1, PLN

Tolvaptan

hsa05415

Diabetic cardiomyopathy

1.28E-02

Q16718, O14521, Q16539, P49841

NDUFA5, SDHD, MAPK14, GSK3B

Tolvaptan

hsa05418

Fluid shear stress and atherosclerosis

2.62E-02

Q16539, P10599, P14780, P04637, P14778, P27930

MAPK14, TXN, MMP9, TP53, IL1R1, IL1R2

Community members of Tolvaptan (S_DC: 7.33)

UniProtAC

Gene Name

Protein Name

Reported/
Predicted

S_PV

PYGL

Glycogen phosphorylase, liver form

Predicted

0.3733

0.2211

0.3169

0.9457

P61586

RHOA

Transforming protein RhoA

Predicted

0.3541

0.0689

1.3149

P21730

C5AR1

C5a anaphylatoxin chemotactic receptor 1

Predicted

0.0258

0.2167

0.5396

0.986

Q16581

C3AR1

C3a anaphylatoxin chemotactic receptor

Predicted

0.1388

0.0385

0.3428

0.4892

P14780

MMP9

Matrix metalloproteinaseNone9

Predicted

0.1696

0.8424

0.7315

2.5012

P08238

HSP90AB1

Heat shock protein HSP 90Nonebeta

Predicted

0.0611

0.5208

0.741

1.8131

Q16539

MAPK14

MitogenNoneactivated protein kinase 14

Predicted

0.0149

3.0075

O00767

SCD

StearoylNoneCoA desaturase

Predicted

0.1686

0.187

0.1997

0.6581

P08235

NR3C2

Mineralocorticoid receptor

Predicted

0.1855

0.0137

2.1064

P49354

FNTA

Protein farnesyltransferase/geranylgeranyltransferase typeNone1 subunit alpha

Predicted

0.5303

0.7588

1.7827

Q9P1W9

PIM2

Serine/threonineNoneprotein kinase pimNone2

Predicted

0.1267

0.7674

0.2638

1.8619

P31645

SLC6A4

SodiumNonedependent serotonin transporter

Predicted

0.0477

0.0203

2.0442

P09619

PDGFRB

PlateletNonederived growth factor receptor beta

Predicted

0.0496

0.9444

0.7408

2.6543

P50052

AGTR2

TypeNone2 angiotensin II receptor

Predicted

0.0604

0.4365

0.1541

1.0572

P06239

LCK

TyrosineNoneprotein kinase Lck

Predicted

0.0576

0.7287

2.7575

P07900

HSP90AA1

Heat shock protein HSP 90Nonealpha

Predicted

0.4727

0.6064

0.741

2.1901

Q13547

HDAC1

Histone deacetylase 1

Predicted

0.0447

0.986

3.0084

Q92769

HDAC2

Histone deacetylase 2

Predicted

0.0473

0.986

3.0097

P42330

AKR1C3

AldoNoneketo reductase family 1 member C3

Predicted

0.4017

0.8348

0.1748

2.0453

P11712

CYP2C9

Cytochrome P450 2C9

Predicted

0.0106

0.1524

2.1577

P00734

Prothrombin

Predicted

0.0963

0.707

0.4977

1.9598

PharmaCoNets of Tolvaptan (SPCN: 131.17 )

Tolvaptan regulated-network (SDN: 17.89)

Community members of Tolvaptan (SDC: 7.33)

PharmaCoNets of Tolvaptan (S_PCN: 131.17 )

Tolvaptan regulated-network (S_DN: 17.89)

Community members of Tolvaptan (S_DC: 7.33)