PharmaCoNets

PharmaCoNets of Caffeine (S_PCN: 107.67 )

Caffeine regulated-network (S_DN: 18.25)

Drug Name

Pathway ID

Pathway name

P-value

No. of gene members

UniProt AC

Gene name

Detail of Coexpression

Caffeine

hsa00030

Pentose phosphate pathway

3.06E-04

P60891, P51854, P37837

PRPS1, TKTL1, TALDO1

Caffeine

hsa00052

Galactose metabolism

4.27E-02

P06280, O43451

GLA, MGAM

Caffeine

hsa00053

Ascorbate and aldarate metabolism

4.93E-02

P14550

AKR1A1

Caffeine

hsa00190

Oxidative phosphorylation

4.21E-04

Q16718, Q13488, P36542, O14521

NDUFA5, TCIRG1, ATP5C1, SDHD

Caffeine

hsa00220

Arginine biosynthesis

1.21E-02

P15104

GLUL

Caffeine

hsa00250

Alanine, aspartate and glutamate metabolism

2.42E-02

P15104

GLUL

Caffeine

hsa00340

Histidine metabolism

3.28E-02

O95954

FTCD

Caffeine

hsa00500

Starch and sucrose metabolism

6.17E-03

O43451, P46976, P06737

MGAM, GYG1, PYGL

Caffeine

hsa00565

Ether lipid metabolism

4.93E-02

Q8N661

TMEM86B

Caffeine

hsa00600

Sphingolipid metabolism

2.77E-02

Q9BX95, Q8TCT0, P15289

SGPP1, CERK, ARSA

Caffeine

hsa00630

Glyoxylate and dicarboxylate metabolism

4.84E-04

P40925, P40926, P15104

MDH1, MDH2, GLUL

Caffeine

hsa00670

One carbon pool by folate

4.88E-02

O95954

FTCD

Caffeine

hsa00730

Thiamine metabolism

2.27E-02

P05186, P24666

ALPL, ACP1

Caffeine

hsa00910

Nitrogen metabolism

2.42E-02

P15104

GLUL

Caffeine

hsa00983

Drug metabolism - other enzymes

5.93E-05

P04183, P32320, P05164

TK1, CDA, MPO

Caffeine

hsa01040

Biosynthesis of unsaturated fatty acids

2.92E-02

P22307, Q9H5J4

SCP2, ELOVL6

Caffeine

hsa01200

Carbon metabolism

4.32E-02

P51854, P37837, P60891

TKTL1, TALDO1, PRPS1

Caffeine

hsa01230

Biosynthesis of amino acids

1.16E-03

P51854, P60891, P15104, P37837

TKTL1, PRPS1, GLUL, TALDO1

Caffeine

hsa01522

Endocrine resistance

5.79E-03

P22694, Q02750, Q9UM47, P46527, P10415, Q13323

PRKACB, MAP2K1, NOTCH3, CDKN1B, BCL2, BIK

Caffeine

hsa02010

ABC transporters

4.93E-02

Q8IZY2

ABCA7

Caffeine

hsa03013

RNA transport

1.39E-04

O14980, Q09161, O14893, Q7Z3B4, P35658, P47813, Q14152, O75822, Q14240, Q9BZI7, Q06787, P51114

XPO1, NCBP1, GEMIN2, NUP54, NUP214, EIF1AX, EIF3A, EIF3J, EIF4A2, UPF3B, FMR1, FXR1

Caffeine

hsa03022

Basal transcription factors

3.50E-02

P20226, O00268, Q15544

TBP, TAF4, TAF11

Caffeine

hsa03040

Spliceosome

1.34E-04

Q14562, O43143, O60508, P17844, P08579, O75940, P51991, P61978, O75494, Q07955, Q01130, Q13243, P11142, O43447

DHX8, DHX15, CDC40, DDX5, SNRPB2, SMNDC1, HNRPA3, HNRPK, FUSIP1, SFRS1, SFRS2, SFRS5, HSPA8, PPIH

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
Q13370	PDE3B	cGMP-inhibited 3',5'-cyclic phosphodiesterase B	Q14562	DHX8	ATP-dependent RNA helicase DHX8	-0.853
P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	Q14562	DHX8	ATP-dependent RNA helicase DHX8	-0.708
Q13370	PDE3B	cGMP-inhibited 3',5'-cyclic phosphodiesterase B	O43143	DHX15	ATP-dependent RNA helicase DHX15	-0.818
P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	O60508	CDC40	Pre-mRNA-processing factor 17	-0.837
P07900	HSP90AA1	Heat shock protein HSP 90-alpha	P17844	DDX5	Probable ATP-dependent RNA helicase DDX5	0.73
P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	P08579	SNRPB2	U2 small nuclear ribonucleoprotein B''	-0.702
Q13370	PDE3B	cGMP-inhibited 3',5'-cyclic phosphodiesterase B	O75940	SMNDC1	Survival of motor neuron-related-splicing factor 30	0.786
P07900	HSP90AA1	Heat shock protein HSP 90-alpha	P51991	HNRPA3	Heterogeneous nuclear ribonucleoprotein A3	0.787
P07900	HSP90AA1	Heat shock protein HSP 90-alpha	P61978	HNRPK	Heterogeneous nuclear ribonucleoprotein K	0.827
Q13370	PDE3B	cGMP-inhibited 3',5'-cyclic phosphodiesterase B	O75494	FUSIP1	Serine/arginine-rich splicing factor 10	0.73
Q13370	PDE3B	cGMP-inhibited 3',5'-cyclic phosphodiesterase B	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	-0.776
Q13370	PDE3B	cGMP-inhibited 3',5'-cyclic phosphodiesterase B	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	-0.758
P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	-0.835
Q13370	PDE3B	cGMP-inhibited 3',5'-cyclic phosphodiesterase B	Q13243	SFRS5	Serine/arginine-rich splicing factor 5	-0.87
P07900	HSP90AA1	Heat shock protein HSP 90-alpha	P11142	HSPA8	Heat shock cognate 71 kDa protein	0.709
P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	O43447	PPIH	Peptidyl-prolyl cis-trans isomerase H	-0.761

Caffeine

hsa03050

Proteasome

4.83E-02

P55036

PSMD4

Caffeine

hsa03450

Non-homologous end-joining

4.48E-03

P78527

PRKDC

Caffeine

hsa04014

Ras signaling pathway

2.21E-03

Q02750, P20827, Q15389, Q9NRA1, P49767, P17252, P21359, P0DP23, P62873, P62879, P19174, P22694

MAP2K1, EFNA1, ANGPT1, PDGFC, VEGFC, PRKCA, NF1, CALM1, GNB1, GNB2, PLCG1, PRKACB

Caffeine

hsa04015

Rap1 signaling pathway

4.58E-02

P20827, Q9NRA1, P49767, P0DP23, P17252, P19174

EFNA1, PDGFC, VEGFC, CALM1, PRKCA, PLCG1

Caffeine

hsa04020

Calcium signaling pathway

2.01E-02

P17252, P19174, P0DP23, P20020, Q9NRA1, P49767

PRKCA, PLCG1, CALM1, ATP2B1, PDGFC, VEGFC

Caffeine

hsa04061

Viral protein interaction with cytokine and cytokine receptor

1.84E-02

P51684, P32248, P09341, P02775, P25025, P47992, Q9UBD3

CCR6, CCR7, CXCL1, PPBP, CXCR2, XCL1, XCL2

Caffeine

hsa04064

NF-kappa B signaling pathway

2.78E-04

P10415, Q13489, O00463, Q04759, Q9UDY8, Q13077, Q16548, Q8WV28, Q13315, P24522, P09341

BCL2, BIRC3, TRAF5, PRKCQ, MALT1, TRAF1, BCL2A1, BLNK, ATM, GADD45A, CXCL1

Caffeine

hsa04066

HIF-1 signaling pathway

4.48E-02

P17252, Q15389, Q02750, P46527

PRKCA, ANGPT1, MAP2K1, CDKN1B

Caffeine

hsa04070

Phosphatidylinositol signaling system

4.40E-02

P19174, P0DP23, P23743, P17252

PLCG1, CALM1, DGKA, PRKCA

Caffeine

hsa04071

Sphingolipid signaling pathway

6.78E-05

P17252, P21453, Q9H228, P01375, Q13362, Q9BX95, Q16539, P10415

PRKCA, S1PR1, EDG8, TNF, PPP2R5C, SGPP1, MAPK14, BCL2

Caffeine

hsa04080

Neuroactive ligand-receptor interaction

4.68E-05

P08311, P28472, Q15722, P21453, Q9H228, O00398, P21730, Q16581, P07550

CTSG, GABRB3, LTB4R, S1PR1, EDG8, P2RY10, C5AR1, C3AR1, ADRB2

Caffeine

hsa04110

Cell cycle

1.35E-02

P78527

PRKDC

Caffeine

hsa04115

p53 signaling pathway

3.98E-02

P24522, Q13315, Q53FA7, O95067, P10415

GADD45A, ATM, TP53I3, CCNB2, BCL2

Caffeine

hsa04140

Autophagy - animal

4.74E-02

P22694, Q14643, P10415

PRKACB, ITPR1, BCL2

Caffeine

hsa04141

Protein processing in endoplasmic reticulum

1.91E-03

P18848, Q15437, Q99941, P11142, P07900, Q9NR31

ATF4, SEC23B, CREBL1, HSPA8, HSP90AA1, SAR1A

Caffeine

hsa04142

Lysosome

4.27E-03

Q99437, P08311, P43234, P25774, Q9UBR2, P06280, P49279, Q9Y6Q5, Q9UPM8

ATP6V0B, CTSG, CTSO, CTSS, CTSZ, GLA, SLC11A1, AP1M2, AP4E1

Caffeine

hsa04145

Phagosome

1.83E-02

Q15080, P14598, Q13509, P68371, Q13488, Q99437, P25774

NCF4, NCF1, TUBB3, TUBB2C, TCIRG1, ATP6V0B, CTSS

Caffeine

hsa04146

Peroxisome

4.83E-02

O96011, P56589, Q9UKG9, O75521

PEX11B, PEX3, CROT, ECI2

Caffeine

hsa04151

PI3K-Akt signaling pathway

3.91E-03

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

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

Caffeine

hsa04210

Apoptosis

4.99E-03

Q13315, P10415, Q13489, O76075, P24522, Q16548, Q13077, P43234, Q9UBR2, P18848, Q14643

ATM, BCL2, BIRC3, DFFB, GADD45A, BCL2A1, TRAF1, CTSO, CTSZ, ATF4, ITPR1

Caffeine

hsa04211

Longevity regulating pathway

2.72E-02

P51828, Q99941, P18848

ADCY7, CREBL1, ATF4

Caffeine

hsa04217

Necroptosis

1.36E-02

P01568, P42224, P08238, Q6FI13, Q93077, O43633, Q08752

IFNA21, STAT1, HSP90AB1, H2AC18; H2AC19, HIST1H2AC, CHMP2A, PPID

Caffeine

hsa04261

Adrenergic signaling in cardiomyocytes

1.33E-03

P07550, P51828, P22694, Q99941, P18848, Q13362, Q13557

ADRB2, ADCY7, PRKACB, CREBL1, ATF4, PPP2R5C, CAMK2D

Caffeine

hsa04340

Hedgehog signaling pathway

9.74E-03

P22694, Q13635, P10415

PRKACB, PTCH1, BCL2

Caffeine

hsa04350

TGF-beta signaling pathway

4.88E-02

P37173

TGFBR2

Caffeine

hsa04360

Axon guidance

2.88E-03

P20936, P16333, P20827, O95631, P17252, P34925, P19174

RASA1, NCK1, EFNA1, NTN1, PRKCA, RYK, PLCG1

Caffeine

hsa04380

Osteoclast differentiation

1.02E-02

Q9UQC2, Q16539, P14778, O75015, P01375, Q8N149

GAB2, MAPK14, IL1R1, FCGR3B, TNF, LILRA2

Caffeine

hsa04540

Gap junction

8.54E-05

P17252, P22694, Q13509, P68371, Q02750, Q9NRA1, Q14643

PRKCA, PRKACB, TUBB3, TUBB2C, MAP2K1, PDGFC, ITPR1

Caffeine

hsa04610

Complement and coagulation cascades

2.33E-03

P0C0L4

C4A

Caffeine

hsa04612

Antigen processing and presentation

4.24E-05

P13765, P48382, Q14953, P26715, P26717, Q13241, O43908, P01732, P01375

HLA-DOB, RFX5, KIR2DS5, KLRC1, KLRC2, KLRD1, KLRC4, CD8A, TNF

Caffeine

hsa04613

Neutrophil extracellular trap formation

1.55E-03

P17252, O60603, P05164, P08246, Q9UM07, Q6FI13, Q15080, P20160, P08311, P21730, P21462, O43315, Q16539

PRKCA, TLR2, MPO, ELA2, PADI4, H2AC18; H2AC19, NCF4, AZU1, CTSG, C5AR1, FPR1, AQP9, MAPK14

Caffeine

hsa04614

Renin-angiotensin system

1.52E-02

P50052

AGTR2

Caffeine

hsa04621

NOD-like receptor signaling pathway

2.27E-02

Q9H1Y0, P43490, O00463, Q05823, P01375, P49913, P59665, P59666, P12838

ATG5, PBEF1, TRAF5, RNASEL, TNF, CAMP, DEFA1; DEFA1B, DEFA3, DEFA4

Caffeine

hsa04623

Cytosolic DNA-sensing pathway

3.29E-02

P01568, P25963

IFNA21, NFKBIA

Caffeine

hsa04625

C-type lectin receptor signaling pathway

3.87E-02

Q9ULY5, P20749, P01375, Q16539

CLEC4E, BCL3, TNF, MAPK14

Caffeine

hsa04650

Natural killer cell mediated cytotoxicity

4.40E-05

P01375, O60880, P20963, Q13241, P26718, O75015, P26717, Q14953, P26715

TNF, SH2D1A, CD247, KLRD1, KLRK1, FCGR3B, KLRC2, KIR2DS5, KLRC1

Caffeine

hsa04657

IL-17 signaling pathway

8.78E-05

P25963, P08238, O00463, Q07955, Q16539, P49841, P19875, P14780, P04141, P80188, P01375, P06702

NFKBIA, HSP90AB1, TRAF5, SFRS1, MAPK14, GSK3B, CXCL2, MMP9, CSF2, LCN2, TNF, S100A9

Caffeine

hsa04658

Th1 and Th2 cell differentiation

1.30E-02

Q04759, P09693, Q16539, Q14765, P23771, Q9UL17, P13765

PRKCQ, CD3G, MAPK14, STAT4, GATA3, TBX21, HLA-DOB

Caffeine

hsa04659

Th17 cell differentiation

8.77E-03

Q04759, Q9HBE5, P84022

PRKCQ, IL21R, SMAD3

Caffeine

hsa04660

T cell receptor signaling pathway

3.54E-03

P04141, P25963, Q9UDY8, Q04759, P10747, O95267, Q08881, P19174, P16333, P09693, P01732, P29350, Q16539

CSF2, NFKBIA, MALT1, PRKCQ, CD28, RASGRP1, ITK, PLCG1, NCK1, CD3G, CD8A, PTPN6, MAPK14

Caffeine

hsa04662

B cell receptor signaling pathway

1.49E-03

P42338, P60033, P07948, P21854, Q8N149

PIK3CB, CD81, LYN, CD72, LILRA2

Caffeine

hsa04664

Fc epsilon RI signaling pathway

2.20E-03

P01375, Q16539, P42338, Q9UQC2, P07948, P09917

TNF, MAPK14, PIK3CB, GAB2, LYN, ALOX5

Caffeine

hsa04668

TNF signaling pathway

2.12E-03

P01375, O00463, Q16539, P18848, P19875, P20749, P14780

TNF, TRAF5, MAPK14, ATF4, CXCL2, BCL3, MMP9

Caffeine

hsa04670

Leukocyte transendothelial migration

4.37E-02

P14780, P13612, P17252, Q16539, Q15080, Q08881, P42681

MMP9, ITGA4, PRKCA, MAPK14, NCF4, ITK, TXK

Caffeine

hsa04672

Intestinal immune network for IgA production

1.55E-02

P10747, P13765, P13612

CD28, HLA-DOB, ITGA4

Caffeine

hsa04713

Circadian entrainment

3.32E-02

P0DP23, P17252, P62873, O15055

CALM1, PRKCA, GNB1, PER2

Caffeine

hsa04714

Thermogenesis

3.31E-02

P51828, P62753, P12074, O15239

ADCY7, RPS6, COX6A1, NDUFA1

Caffeine

hsa04720

Long-term potentiation

1.09E-02

P17252, P51812, P22694, Q02750

PRKCA, RPS6KA3, PRKACB, MAP2K1

Caffeine

hsa04723

Retrograde endocannabinoid signaling

2.28E-02

Q14643, P17252, P22694, Q16539, Q16718

ITPR1, PRKCA, PRKACB, MAPK14, NDUFA5

Caffeine

hsa04724

Glutamatergic synapse

5.94E-03

O15399, P63218, P50151, P15104

GRIN2D, GNG5, GNG10, GLUL

Caffeine

hsa04725

Cholinergic synapse

4.09E-06

P51828, P22694, Q14643, P17252, P62879, P63218, P50151, P18848, Q13557, P42338, P10415, Q02750

ADCY7, PRKACB, ITPR1, PRKCA, GNB2, GNG5, GNG10, ATF4, CAMK2D, PIK3CB, BCL2, MAP2K1

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
P07900	HSP90AA1	Heat shock protein HSP 90-alpha	P51828	ADCY7	Adenylate cyclase type 7	0.726
Q13315	ATM	Serine-protein kinase ATM	P22694	PRKACB	cAMP-dependent protein kinase catalytic subunit beta	0.858
P21453	S1PR1	Sphingosine 1-phosphate receptor 1	P22694	PRKACB	cAMP-dependent protein kinase catalytic subunit beta	0.71
P05164	MPO	Myeloperoxidase	P22694	PRKACB	cAMP-dependent protein kinase catalytic subunit beta	-0.817
P21453	S1PR1	Sphingosine 1-phosphate receptor 1	Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	0.768
P05164	MPO	Myeloperoxidase	Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	-0.818
Q13315	ATM	Serine-protein kinase ATM	P17252	PRKCA	Protein kinase C alpha type	0.739
Q13315	ATM	Serine-protein kinase ATM	P62879	GNB2	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2	-0.716
P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	0.747
P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	0.752
P05164	MPO	Myeloperoxidase	P18848	ATF4	Cyclic AMP-dependent transcription factor ATF-4	0.732
P07900	HSP90AA1	Heat shock protein HSP 90-alpha	P18848	ATF4	Cyclic AMP-dependent transcription factor ATF-4	0.783
P07900	HSP90AA1	Heat shock protein HSP 90-alpha	Q13557	CAMK2D	Calcium/calmodulin-dependent protein kinase type II subunit delta	0.763
P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	1
P21453	S1PR1	Sphingosine 1-phosphate receptor 1	P10415	BCL2	Apoptosis regulator Bcl-2	0.723
P05164	MPO	Myeloperoxidase	P10415	BCL2	Apoptosis regulator Bcl-2	-0.81
Q13315	ATM	Serine-protein kinase ATM	Q02750	MAP2K1	Dual specificity mitogen-activated protein kinase kinase 1	-0.797

Caffeine

hsa04726

Serotonergic synapse

2.43E-02

P22694, P17252, P62879, Q02750

PRKACB, PRKCA, GNB2, MAP2K1

Caffeine

hsa04727

GABAergic synapse

1.08E-03

P62879, P63218, P50151, P15104, P22694, O60296, P17252

GNB2, GNG5, GNG10, GLUL, PRKACB, TRAK2, PRKCA

Caffeine

hsa04728

Dopaminergic synapse

4.78E-02

Q99941, P18848, Q13557

CREBL1, ATF4, CAMK2D

Caffeine

hsa04744

Phototransduction

1.18E-02

P62873, P0DP23

GNB1, CALM1

Caffeine

hsa04750

Inflammatory mediator regulation of TRP channels

3.39E-02

P22694, Q16539, Q14643, P17252, Q04759

PRKACB, MAPK14, ITPR1, PRKCA, PRKCQ

Caffeine

hsa04911

Insulin secretion

4.03E-04

P51828, Q99941, P18848, Q13557

ADCY7, CREBL1, ATF4, CAMK2D

Caffeine

hsa04912

GnRH signaling pathway

4.73E-03

P17252, P51828, P18848, Q13557, Q16539, Q14643, P22694

PRKCA, ADCY7, ATF4, CAMK2D, MAPK14, ITPR1, PRKACB

Caffeine

hsa04913

Ovarian steroidogenesis

1.27E-03

P42330, P22694

AKR1C3, PRKACB

Caffeine

hsa04915

Estrogen signaling pathway

9.55E-04

P14780, P22694, Q99941, P18848, P51828, P07900, P11142, Q14643, P10415

MMP9, PRKACB, CREBL1, ATF4, ADCY7, HSP90AA1, HSPA8, ITPR1, BCL2

Caffeine

hsa04918

Thyroid hormone synthesis

6.10E-04

P22694, P51828, Q99941, P18848, Q14643, P02768

PRKACB, ADCY7, CREBL1, ATF4, ITPR1, ALB

Caffeine

hsa04919

Thyroid hormone signaling pathway

2.22E-02

P17252, Q02750, P22694, Q12778, Q9UM47

PRKCA, MAP2K1, PRKACB, FOXO1, NOTCH3

Caffeine

hsa04922

Glucagon signaling pathway

4.80E-02

P22694, P06737, Q12778, Q14643, P07195

PRKACB, PYGL, FOXO1, ITPR1, LDHB

Caffeine

hsa04924

Renin secretion

2.90E-04

P22694, P07550, Q14643

PRKACB, ADRB2, ITPR1

Caffeine

hsa04925

Aldosterone synthesis and secretion

1.69E-03

Q99941, P18848, P51828, Q13557

CREBL1, ATF4, ADCY7, CAMK2D

Caffeine

hsa04926

Relaxin signaling pathway

3.75E-05

P42338, P63218, P50151, Q99941, P18848, P22694, P49767, P14780, P51828, P30679, P49407

PIK3CB, GNG5, GNG10, CREBL1, ATF4, PRKACB, VEGFC, MMP9, ADCY7, GNA15, ARRB1

Caffeine

hsa04927

Cortisol synthesis and secretion

6.24E-07

Q14643, Q99941, P18848, P51828, P22694

ITPR1, CREBL1, ATF4, ADCY7, PRKACB

Caffeine

hsa04928

Parathyroid hormone synthesis, secretion and action

2.23E-06

Q14643, P51828, P22694, P23771, Q02750, P17252, Q99941, P18848, P10415, Q9Y5Q3

ITPR1, ADCY7, PRKACB, GATA3, MAP2K1, PRKCA, CREBL1, ATF4, BCL2, MAFB

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
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	1
P21453	S1PR1	Sphingosine 1-phosphate receptor 1	Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	0.768
P05164	MPO	Myeloperoxidase	Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	-0.818
P07900	HSP90AA1	Heat shock protein HSP 90-alpha	P51828	ADCY7	Adenylate cyclase type 7	0.726
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	P22694	PRKACB	cAMP-dependent protein kinase catalytic subunit beta	0.816
Q13315	ATM	Serine-protein kinase ATM	P22694	PRKACB	cAMP-dependent protein kinase catalytic subunit beta	0.858
P21453	S1PR1	Sphingosine 1-phosphate receptor 1	P22694	PRKACB	cAMP-dependent protein kinase catalytic subunit beta	0.71
P05164	MPO	Myeloperoxidase	P22694	PRKACB	cAMP-dependent protein kinase catalytic subunit beta	-0.817
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	0.873
P21453	S1PR1	Sphingosine 1-phosphate receptor 1	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	0.778
P05164	MPO	Myeloperoxidase	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.871
Q13315	ATM	Serine-protein kinase ATM	Q02750	MAP2K1	Dual specificity mitogen-activated protein kinase kinase 1	-0.797
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	P17252	PRKCA	Protein kinase C alpha type	0.786
Q13315	ATM	Serine-protein kinase ATM	P17252	PRKCA	Protein kinase C alpha type	0.739
P07900	HSP90AA1	Heat shock protein HSP 90-alpha	Q99941	CREBL1	Cyclic AMP-dependent transcription factor ATF-6 beta	0.777
P05164	MPO	Myeloperoxidase	P18848	ATF4	Cyclic AMP-dependent transcription factor ATF-4	0.732
P07900	HSP90AA1	Heat shock protein HSP 90-alpha	P18848	ATF4	Cyclic AMP-dependent transcription factor ATF-4	0.783
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	P10415	BCL2	Apoptosis regulator Bcl-2	0.858
P21453	S1PR1	Sphingosine 1-phosphate receptor 1	P10415	BCL2	Apoptosis regulator Bcl-2	0.723
P05164	MPO	Myeloperoxidase	P10415	BCL2	Apoptosis regulator Bcl-2	-0.81
Q13315	ATM	Serine-protein kinase ATM	Q9Y5Q3	MAFB	Transcription factor MafB	0.706

Caffeine

hsa04929

GnRH secretion

4.62E-02

P42338, P49407

PIK3CB, ARRB1

Caffeine

hsa04933

AGE-RAGE signaling pathway in diabetic complications

1.72E-02

P42224, Q12778, P49767, P17252, P19174

STAT1, FOXO1, VEGFC, PRKCA, PLCG1

Caffeine

hsa04934

Cushing syndrome

2.44E-04

Q14643, Q99941, P18848, P51828, P22694, Q13557, P04628

ITPR1, CREBL1, ATF4, ADCY7, PRKACB, CAMK2D, WNT1

Caffeine

hsa04935

Growth hormone synthesis, secretion and action

2.72E-02

P51828, Q99941, P18848

ADCY7, CREBL1, ATF4

Caffeine

hsa04964

Proximal tubule bicarbonate reclamation

4.93E-02

P00918

CA2

Caffeine

hsa04966

Collecting duct acid secretion

4.93E-02

P00918

CA2

Caffeine

hsa04970

Salivary secretion

1.18E-04

P07550, P22694, Q14643, P17252, P49913

ADRB2, PRKACB, ITPR1, PRKCA, CAMP

Caffeine

hsa05012

Parkinson disease

3.12E-02

Q16718, O14521, P19174, P0DP23, Q13509, P68371

NDUFA5, SDHD, PLCG1, CALM1, TUBB3, TUBB2C

Caffeine

hsa05014

Amyotrophic lateral sclerosis

2.72E-02

P01375, Q16718, O14521, P36542, P09651, Q7Z3B4, P35658, P43243, Q09161, Q16629

TNF, NDUFA5, SDHD, ATP5C1, HNRNPA1, NUP54, NUP214, MATR3, NCBP1, SFRS7

Caffeine

hsa05022

Pathways of neurodegeneration - multiple diseases

2.29E-02

Q13509, P68371, Q16718, O14521, Q13561, P19174, P17252, Q08752, P0DP23

TUBB3, TUBB2C, NDUFA5, SDHD, DCTN2, PLCG1, PRKCA, PPID, CALM1

Caffeine

hsa05030

Cocaine addiction

4.87E-02

Q99941, P18848

CREBL1, ATF4

Caffeine

hsa05031

Amphetamine addiction

8.84E-04

Q13557, P22694, Q99941, P18848, Q13547

CAMK2D, PRKACB, CREBL1, ATF4, HDAC1

Caffeine

hsa05110

Vibrio cholerae infection

2.60E-03

Q13488, Q99437, P17252, P19174

TCIRG1, ATP6V0B, PRKCA, PLCG1

Caffeine

hsa05132

Salmonella infection

1.70E-02

P25963, P08238, P04406, O75369, Q13561, Q13509, P68371, P49754

NFKBIA, HSP90AB1, GAPDH, FLNB, DCTN2, TUBB3, TUBB2C, VPS41

Caffeine

hsa05133

Pertussis

4.20E-02

P0C0L4

C4A

Caffeine

hsa05140

Leishmaniasis

1.72E-02

P14598, P42224, P25963, P29350, Q15080

NCF1, STAT1, NFKBIA, PTPN6, NCF4

Caffeine

hsa05143

African trypanosomiasis

1.31E-02

P69905, P68871

HBA2, HBB

Caffeine

hsa05144

Malaria

1.94E-04

P60033, P69905, P68871, P01375, P35443, P26718

CD81, HBA2, HBB, TNF, THBS4, KLRK1

Caffeine

hsa05146

Amoebiasis

2.41E-02

P19875, P01375, P30679, P22694

CXCL2, TNF, GNA15, PRKACB

Caffeine

hsa05150

Staphylococcus aureus infection

1.19E-05

P21730, P21462, O75015, Q14532, P59665, P59666, P12838, P49913

C5AR1, FPR1, FCGR3B, KRT32, DEFA1; DEFA1B, DEFA3, DEFA4, CAMP

Caffeine

hsa05152

Tuberculosis

4.16E-02

Q99437, P25774

ATP6V0B, CTSS

Caffeine

hsa05161

Hepatitis B

3.34E-02

Q99941, P18848, P27348

CREBL1, ATF4, YWHAQ

Caffeine

hsa05163

Human cytomegalovirus infection

2.80E-02

P01375, P49841, P14778, P25025, Q16539, O00463

TNF, GSK3B, IL1R1, CXCR2, MAPK14, TRAF5

Caffeine

hsa05165

Human papillomavirus infection

4.71E-03

P46527, Q02750, P35443, Q92796, Q05086, Q9UM47, P22694, Q13362, Q12778, Q13315

CDKN1B, MAP2K1, THBS4, DLG3, UBE3A, NOTCH3, PRKACB, PPP2R5C, FOXO1, ATM

Caffeine

hsa05167

Kaposi sarcoma-associated herpesvirus infection

5.71E-03

P01568, P42224, P25963, P40189, P62873, P19174, P04141, P0DP23

IFNA21, STAT1, NFKBIA, IL6ST, GNB1, PLCG1, CSF2, CALM1

Caffeine

hsa05168

Herpes simplex virus 1 infection

4.15E-03

P25963, P01568, Q9GZY0, P42224, Q07955, Q01130, Q13243, Q13398, Q03923, P52738, O75820, Q9UDV6

NFKBIA, IFNA21, NXF2; NXF2B, STAT1, SFRS1, SFRS2, SFRS5, ZNF211, ZNF85, ZNF140, ZNF189, ZNF212

Caffeine

hsa05169

Epstein-Barr virus infection

3.72E-02

Q13547, P42338, P07948, Q13761, O75293, P07766

HDAC1, PIK3CB, LYN, RUNX3, GADD45B, CD3E

Caffeine

hsa05171

Coronavirus disease - COVID-19

1.36E-02

P25963, P42224, P01568, P40189, P04141, P19174, P17252

NFKBIA, STAT1, IFNA21, IL6ST, CSF2, PLCG1, PRKCA

Caffeine

hsa05200

Pathways in cancer

1.75E-02

P08238, P42224, P25963, P19174, P17252, P43246, P14923, P49767, Q12778, P62873, O75293, P0DP23, P01568, P40189

HSP90AB1, STAT1, NFKBIA, PLCG1, PRKCA, MSH2, JUP, VEGFC, FOXO1, GNB1, GADD45B, CALM1, IFNA21, IL6ST

Caffeine

hsa05202

Transcriptional misregulation in cancer

1.63E-05

Q12778, Q15532, Q13315, P41732, P14780, Q15744, Q16548, Q13489, Q13077, O15550, P46527, P35226, P05164, P12838, P08246, Q9C0K0, P24522

FOXO1, SS18, ATM, TSPAN7, MMP9, CEBPE, BCL2A1, BIRC3, TRAF1, UTX, CDKN1B, BMI1, MPO, DEFA4, ELA2, BCL11B, 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
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	Q12778	FOXO1	Forkhead box protein O1	0.729
Q13315	ATM	Serine-protein kinase ATM	Q12778	FOXO1	Forkhead box protein O1	0.821
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	Q15532	SS18	Protein SSXT	0.771
P05164	MPO	Myeloperoxidase	Q15532	SS18	Protein SSXT	-0.719
Q13315	ATM	Serine-protein kinase ATM	Q13315	ATM	Serine-protein kinase ATM	1
P05164	MPO	Myeloperoxidase	Q13315	ATM	Serine-protein kinase ATM	-0.725
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	P41732	TSPAN7	Tetraspanin-7	-0.789
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	P14780	MMP9	Matrix metalloproteinase-9	-0.81
P05164	MPO	Myeloperoxidase	P14780	MMP9	Matrix metalloproteinase-9	0.812
Q13315	ATM	Serine-protein kinase ATM	Q15744	CEBPE	CCAAT/enhancer-binding protein epsilon	-0.709
P05164	MPO	Myeloperoxidase	Q15744	CEBPE	CCAAT/enhancer-binding protein epsilon	0.799
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	Q16548	BCL2A1	Bcl-2-related protein A1	-0.822
P05164	MPO	Myeloperoxidase	Q16548	BCL2A1	Bcl-2-related protein A1	0.782
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	0.701
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	Q13077	TRAF1	TNF receptor-associated factor 1	0.768
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	O15550	UTX	Lysine-specific demethylase 6A	-0.767
P05164	MPO	Myeloperoxidase	O15550	UTX	Lysine-specific demethylase 6A	0.763
Q13315	ATM	Serine-protein kinase ATM	P46527	CDKN1B	Cyclin-dependent kinase inhibitor 1B	0.708
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	P35226	BMI1	Polycomb complex protein BMI-1	0.703
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	P35226	BMI1	Polycomb complex protein BMI-1	0.703
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	P05164	MPO	Myeloperoxidase	-0.818
Q13315	ATM	Serine-protein kinase ATM	P05164	MPO	Myeloperoxidase	-0.725
P05164	MPO	Myeloperoxidase	P05164	MPO	Myeloperoxidase	1
P05164	MPO	Myeloperoxidase	P12838	DEFA4	Neutrophil defensin 4	0.733
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	P08246	ELA2	Neutrophil elastase	-0.816
Q13315	ATM	Serine-protein kinase ATM	P08246	ELA2	Neutrophil elastase	-0.742
P05164	MPO	Myeloperoxidase	P08246	ELA2	Neutrophil elastase	0.903
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	Q9C0K0	BCL11B	B-cell lymphoma/leukemia 11B	0.925
Q13315	ATM	Serine-protein kinase ATM	Q9C0K0	BCL11B	B-cell lymphoma/leukemia 11B	0.741
P05164	MPO	Myeloperoxidase	Q9C0K0	BCL11B	B-cell lymphoma/leukemia 11B	-0.854
Q14643	ITPR1	Inositol 1,4,5-trisphosphate receptor type 1	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	-0.853
P05164	MPO	Myeloperoxidase	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.812

Caffeine

hsa05203

Viral carcinogenesis

1.46E-02

Q99941, P18848, P27348, P61978

CREBL1, ATF4, YWHAQ, HNRPK

Caffeine

hsa05205

Proteoglycans in cancer

3.68E-02

P14780, P01375, P23588, Q13635, P22694

MMP9, TNF, EIF4B, PTCH1, PRKACB

Caffeine

hsa05206

MicroRNAs in cancer

3.66E-02

P46527, Q9UM47, P16070, Q13315, P17252, Q02750

CDKN1B, NOTCH3, CD44, ATM, PRKCA, MAP2K1

Caffeine

hsa05212

Pancreatic cancer

3.40E-02

P37173

TGFBR2

Caffeine

hsa05214

Glioma

1.09E-02

P0DP23, P17252, P19174, O75293

CALM1, PRKCA, PLCG1, GADD45B

Caffeine

hsa05231

Choline metabolism in cancer

2.25E-03

Q9NRA1, Q9Y259, P19174, P23743, P17252

PDGFC, CHKB, PLCG1, DGKA, PRKCA

Caffeine

hsa05235

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

3.98E-03

P25963, O95267, P19174, P09693, P29350, P42224, O60603, P10747, Q04759, Q16539

NFKBIA, RASGRP1, PLCG1, CD3G, PTPN6, STAT1, TLR2, CD28, PRKCQ, MAPK14

Caffeine

hsa05321

Inflammatory bowel disease

2.74E-06

O60603, P01375, P13765, Q14765, Q9UL17, P23771, P84022, Q9HBE5

TLR2, TNF, HLA-DOB, STAT4, TBX21, GATA3, SMAD3, IL21R

Caffeine

hsa05332

Graft-versus-host disease

9.06E-06

P13765, P10747, P01375, P26715, Q13241

HLA-DOB, CD28, TNF, KLRC1, KLRD1

Caffeine

hsa05340

Primary immunodeficiency

3.73E-02

P11912, P16871

CD79A, IL7R

Caffeine

hsa05412

Arrhythmogenic right ventricular cardiomyopathy

4.93E-02

P54284

CACNB3

Caffeine

hsa05415

Diabetic cardiomyopathy

1.20E-02

P17252, P14598, Q15080, Q16718, O14521, P04406

PRKCA, NCF1, NCF4, NDUFA5, SDHD, GAPDH

Caffeine

hsa05418

Fluid shear stress and atherosclerosis

1.08E-03

Q16539, Q14145, P10599, P14780, P01375, P14778, P27930

MAPK14, KEAP1, TXN, MMP9, TNF, IL1R1, IL1R2

Community members of Caffeine (S_DC: 5.90)

UniProtAC

Gene Name

Protein Name

Reported/
Predicted

S_PV

PDE4B

cAMPNonespecific 3',5'Nonecyclic phosphodiesterase 4B

Reported

0.0253

0.9946

0.22

2.2219

Q13370

PDE3B

cGMPNoneinhibited 3',5'Nonecyclic phosphodiesterase B

Reported

0.0906

0.1614

0.3558

0.7239

P78527

PRKDC

DNANonedependent protein kinase catalytic subunit

Reported

0.178

0.1944

0.2496

0.7273

P42338

PIK3CB

Phosphatidylinositol 4,5Nonebisphosphate 3Nonekinase catalytic subunit beta isoform

Reported

0.0447

0.9416

2.9055

Q14643

ITPR1

Inositol 1,4,5Nonetrisphosphate receptor type 1

Reported

0.0464

0.012

1.0472

Q13315

ATM

SerineNoneprotein kinase ATM

Reported

0.7747

0.2014

0.9391

1.7293

Q13231

CHIT1

ChitotriosidaseNone1

Predicted

0.0357

0.0429

0.1963

0.3

P00918

CA2

Carbonic anhydrase 2

Predicted

0.1125

0.2215

2.2778

P50052

AGTR2

TypeNone2 angiotensin II receptor

Predicted

0.0604

0.4365

0.1541

1.0572

P07900

HSP90AA1

Heat shock protein HSP 90Nonealpha

Predicted

0.4727

0.6064

0.741

2.1901

P21453

S1PR1

Sphingosine 1Nonephosphate receptor 1

Predicted

0.1434

0.3847

0.221

1.0621

P25774

CTSS

Cathepsin S

Predicted

0.3185

0.4932

0.5168

1.6625

P49841

GSK3B

Glycogen synthase kinaseNone3 beta

Predicted

0.1678

3.0839

Q96EB6

SIRT1

NADNonedependent protein deacetylase sirtuinNone1

Predicted

0.2865

0.4571

0.5784

1.6358

Q14790

CASP8

CaspaseNone8

Predicted

0.15

0.0558

1.1867

P01375

TNF

Tumor necrosis factor

Predicted

0.1865

0.551

2.1953

P05164

MPO

Myeloperoxidase

Predicted

0.2035

0.5368

0.5502

1.7255

Q92736

RYR2

Ryanodine receptor 2

Predicted

0.3011

0.0221

0.4706

0.6655

P07550

ADRB2

BetaNone2 adrenergic receptor

Predicted

0.0071

0.2205

2.224

Gene name	UniProt_ID	Bioactivity	Value (nM)
PRKDC	P78527	IC50	10000000
ATM	Q13315	IC50	200000

PharmaCoNets of Caffeine (SPCN: 107.67 )

Caffeine regulated-network (SDN: 18.25)

Community members of Caffeine (SDC: 5.90)

PharmaCoNets of Caffeine (S_PCN: 107.67 )

Caffeine regulated-network (S_DN: 18.25)

Community members of Caffeine (S_DC: 5.90)