PharmaCoNets

PharmaCoNets of Methotrexate (S_PCN: 61.12 )

Methotrexate regulated-network (S_DN: 18.36)

Drug Name

Pathway ID

Pathway name

P-value

No. of gene members

UniProt AC

Gene name

Detail of Coexpression

Methotrexate

hsa00030

Pentose phosphate pathway

6.21E-04

P52209, P11413, P37837

PGD, G6PD, TALDO1

Methotrexate

hsa00052

Galactose metabolism

1.03E-02

P06280, O43451

GLA, MGAM

Methotrexate

hsa00190

Oxidative phosphorylation

3.27E-02

Q16718, Q13488, O14521

NDUFA5, TCIRG1, SDHD

Methotrexate

hsa00230

Purine metabolism

4.02E-02

P31350, P21589

RRM2, NT5E

Methotrexate

hsa00240

Pyrimidine metabolism

2.54E-04

P31350, P21589, P04818

RRM2, NT5E, TYMS

Methotrexate

hsa00280

Valine, leucine and isoleucine degradation

2.75E-02

P55809, Q9HCC0, Q02252, P11310

OXCT1, MCCC2, ALDH6A1, ACADM

Methotrexate

hsa00310

Lysine degradation

2.59E-02

Q96KQ7, P51648

EHMT2, ALDH3A2

Methotrexate

hsa00480

Glutathione metabolism

1.35E-02

P11413

G6PD

Methotrexate

hsa00500

Starch and sucrose metabolism

1.54E-03

O43451, P46976, P06737

MGAM, GYG1, PYGL

Methotrexate

hsa00512

Mucin type O-glycan biosynthesis

4.86E-02

O95395, Q9NY28

GCNT3, GALNT8

Methotrexate

hsa00531

Glycosaminoglycan degradation

4.51E-02

P22304, P06865

IDS, HEXA

Methotrexate

hsa00600

Sphingolipid metabolism

4.56E-02

Q9BX95, Q06136, P06280

SGPP1, FVT1, GLA

Methotrexate

hsa00630

Glyoxylate and dicarboxylate metabolism

9.62E-04

P40925, P40926, P15104

MDH1, MDH2, GLUL

Methotrexate

hsa00670

One carbon pool by folate

3.62E-02

P00374

DHFR

Methotrexate

hsa00730

Thiamine metabolism

5.29E-03

P05186, P24666

ALPL, ACP1

Methotrexate

hsa00790

Folate biosynthesis

3.62E-02

P00374

DHFR

Methotrexate

hsa00983

Drug metabolism - other enzymes

2.44E-02

P32320, P05164

CDA, MPO

Methotrexate

hsa01100

Metabolic pathways

1.66E-02

Q9Y234, O14521, P15144, Q99707, P11310, P27707, Q13370, P36959, Q13956, P22748, P55809, P06280, P30043, Q02252, O60701, O14772, O95954, Q9HCC0, P33121, P04406, Q96EB6, O15466, P36551, Q9BX95, P09960, Q9P2R7, Q9UHY7, P35573, Q13488, Q16718, Q02809

LIPT1, SDHD, ANPEP, MTR, ACADM, DCK, PDE3B, GMPR, PDE6H, CA4, OXCT1, GLA, BLVRB, ALDH6A1, UGDH, FPGT, FTCD, MCCC2, ACSL1, GAPDH, SIRT1, ST8SIA5, CPOX, SGPP1, LTA4H, SUCLA2, ENOPH1, AGL, TCIRG1, NDUFA5, PLOD1

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
Q99707	MTR	Methionine synthase	Q9Y234	LIPT1	Lipoyltransferase 1, mitochondrial	0.764
Q99707	MTR	Methionine synthase	O14521	SDHD	Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial	0.735
Q99707	MTR	Methionine synthase	P15144	ANPEP	Aminopeptidase N	-0.755
Q99707	MTR	Methionine synthase	Q99707	MTR	Methionine synthase	1
Q99707	MTR	Methionine synthase	P11310	ACADM	Medium-chain specific acyl-CoA dehydrogenase, mitochondrial	0.862
Q99707	MTR	Methionine synthase	P27707	DCK	Deoxycytidine kinase	0.88
Q99707	MTR	Methionine synthase	Q13370	PDE3B	cGMP-inhibited 3',5'-cyclic phosphodiesterase B	0.764
Q99707	MTR	Methionine synthase	P36959	GMPR	GMP reductase 1	-0.819
Q99707	MTR	Methionine synthase	Q13956	PDE6H	Retinal cone rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit gamma	0.869
Q99707	MTR	Methionine synthase	P22748	CA4	Carbonic anhydrase 4	-0.8
Q99707	MTR	Methionine synthase	P55809	OXCT1	Succinyl-CoA:3-ketoacid coenzyme A transferase 1, mitochondrial	0.777
Q99707	MTR	Methionine synthase	P06280	GLA	Alpha-galactosidase A	-0.755
Q99707	MTR	Methionine synthase	P30043	BLVRB	Flavin reductase	-0.802
Q99707	MTR	Methionine synthase	Q02252	ALDH6A1	Methylmalonate-semialdehyde dehydrogenase [acylating], mitochondrial	0.782
Q99707	MTR	Methionine synthase	O60701	UGDH	UDP-glucose 6-dehydrogenase	0.791
Q99707	MTR	Methionine synthase	O14772	FPGT	Fucose-1-phosphate guanylyltransferase	0.818
Q99707	MTR	Methionine synthase	O95954	FTCD	Formimidoyltransferase-cyclodeaminase	-0.825
Q99707	MTR	Methionine synthase	Q9HCC0	MCCC2	Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial	0.782
Q99707	MTR	Methionine synthase	P33121	ACSL1	Long-chain-fatty-acid--CoA ligase 1	-0.737
Q99707	MTR	Methionine synthase	P04406	GAPDH	Glyceraldehyde-3-phosphate dehydrogenase	-0.819
Q99707	MTR	Methionine synthase	Q96EB6	SIRT1	NAD-dependent protein deacetylase sirtuin-1	0.702
Q99707	MTR	Methionine synthase	O15466	ST8SIA5	Alpha-2,8-sialyltransferase 8E	-0.754
Q99707	MTR	Methionine synthase	P36551	CPOX	Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial	0.769
Q99707	MTR	Methionine synthase	Q9BX95	SGPP1	Sphingosine-1-phosphate phosphatase 1	0.833
Q99707	MTR	Methionine synthase	P09960	LTA4H	Leukotriene A-4 hydrolase	-0.771
Q99707	MTR	Methionine synthase	Q9P2R7	SUCLA2	Succinate--CoA ligase [ADP-forming] subunit beta, mitochondrial	0.852
Q99707	MTR	Methionine synthase	Q9UHY7	ENOPH1	Enolase-phosphatase E1	0.803
Q99707	MTR	Methionine synthase	P35573	AGL	Glycogen debranching enzyme	0.718
Q99707	MTR	Methionine synthase	Q13488	TCIRG1	V-type proton ATPase 116 kDa subunit a 3	-0.726
Q99707	MTR	Methionine synthase	Q16718	NDUFA5	NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5	0.931
Q99707	MTR	Methionine synthase	Q02809	PLOD1	Procollagen-lysine,2-oxoglutarate 5-dioxygenase 1	-0.735

Methotrexate

hsa01200

Carbon metabolism

2.91E-02

P11413

G6PD

Methotrexate

hsa01523

Antifolate resistance

6.06E-03

Q92820, P04818

GGH, TYMS

Methotrexate

hsa03010

Ribosome

1.53E-05

P62753, P62906, P46776, Q07020, P61513, P27635, P62249, P23396

RPS6, RPL10A, RPL27A, RPL18, RPL37A, RPL10, RPS16, RPS3

Methotrexate

hsa03013

RNA transport

2.29E-04

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

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

Methotrexate

hsa03040

Spliceosome

4.48E-04

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

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

Methotrexate

hsa03060

Protein export

2.43E-02

Q15070, O76094

OXA1L, SRP72

Methotrexate

hsa04014

Ras signaling pathway

8.66E-03

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

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

Methotrexate

hsa04061

Viral protein interaction with cytokine and cytokine receptor

4.79E-02

P09341, P25024, P25025, P47992, Q9UBD3, P09603

CXCL1, CXCR1, CXCR2, XCL1, XCL2, CSF1

Methotrexate

hsa04062

Chemokine signaling pathway

1.10E-04

P25024, P25025, P09341, P47992, Q9UBD3, P07948, P19174, P62873, P63218, P50151, Q08881, Q13009, P14598, P42224, P25963, P49841

CXCR1, CXCR2, CXCL1, XCL1, XCL2, LYN, PLCG1, GNB1, GNG5, GNG10, ITK, TIAM1, NCF1, STAT1, NFKBIA, 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
P41440	SLC19A1	Reduced folate transporter	P25024	CXCR1	C-X-C chemokine receptor type 1	0.778
P41440	SLC19A1	Reduced folate transporter	P25025	CXCR2	C-X-C chemokine receptor type 2	0.864
P41440	SLC19A1	Reduced folate transporter	P09341	CXCL1	Growth-regulated alpha protein	0.775
P41440	SLC19A1	Reduced folate transporter	P47992	XCL1	Lymphotactin	-0.742
P41440	SLC19A1	Reduced folate transporter	Q9UBD3	XCL2	Cytokine SCM-1 beta	-0.742
P41440	SLC19A1	Reduced folate transporter	P07948	LYN	Tyrosine-protein kinase Lyn	0.729
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P07948	LYN	Tyrosine-protein kinase Lyn	-0.782
P08238	HSP90AB1	Heat shock protein HSP 90-beta	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	0.869
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
P41440	SLC19A1	Reduced folate transporter	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	0.739
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
P41440	SLC19A1	Reduced folate transporter	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	0.722
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
P41440	SLC19A1	Reduced folate transporter	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.745
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
P41440	SLC19A1	Reduced folate transporter	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.747

Methotrexate

hsa04064

NF-kappa B signaling pathway

2.83E-02

P10415, Q13489, O00463, Q13546, Q9UDY8, Q13077, Q16548, P24522

BCL2, BIRC3, TRAF5, RIPK1, MALT1, TRAF1, BCL2A1, GADD45A

Methotrexate

hsa04070

Phosphatidylinositol signaling system

2.93E-02

P19174, P0DP23, P23743, P27987

PLCG1, CALM1, DGKA, ITPKB

Methotrexate

hsa04071

Sphingolipid signaling pathway

5.28E-05

P21453, Q9H228, P01375, Q13362, Q16537, Q9BX95, Q16539, P10415, Q9UQC2

S1PR1, EDG8, TNF, PPP2R5C, PPP2R5E, SGPP1, MAPK14, BCL2, GAB2

Methotrexate

hsa04072

Phospholipase D signaling pathway

3.55E-02

Q9UQC2, Q8WYR1, Q15438, P51828

GAB2, PIK3R5, PSCD1, ADCY7

Methotrexate

hsa04110

Cell cycle

2.34E-02

P06493, O60566, P33981

CDK1, BUB1B, TTK

Methotrexate

hsa04115

p53 signaling pathway

3.34E-02

P31350, P06493

RRM2, CDK1

Methotrexate

hsa04140

Autophagy - animal

3.72E-02

P22694, Q14643, P10415, Q9H1Y0, Q04759

PRKACB, ITPR1, BCL2, ATG5, PRKCQ

Methotrexate

hsa04141

Protein processing in endoplasmic reticulum

3.12E-05

P18848, P30101, Q15437, Q15436, P60604, Q99941, P11142, P07900, P08238, Q9NR31, P14625, Q9H173, Q9UNL2

ATF4, PDIA3, SEC23B, SEC23A, UBE2G2, CREBL1, HSPA8, HSP90AA1, HSP90AB1, SAR1A, HSP90B1, SIL1, SSR3

Methotrexate

hsa04142

Lysosome

3.32E-03

P06865, P22304, Q13510, P07602, P61916, Q04900

HEXA, IDS, ASAH1, PSAP, NPC2, CD164

Methotrexate

hsa04145

Phagosome

5.53E-04

O75015, P11215, Q15075, Q15080, P14598, Q71U36, Q13509, P68371, Q13488, O60603

FCGR3B, ITGAM, EEA1, NCF4, NCF1, TUBA1A, TUBB3, TUBB2C, TCIRG1, TLR2

Methotrexate

hsa04151

PI3K-Akt signaling pathway

4.12E-04

P62753, P27348, P07900, P14625, Q16363, P22105, Q99941, P18848, O00141

RPS6, YWHAQ, HSP90AA1, HSP90B1, LAMA4, TNXB, CREBL1, ATF4, SGK

Methotrexate

hsa04210

Apoptosis

3.58E-02

O76075, P01375, Q9NR28, Q16548

DFFB, TNF, DIABLO, BCL2A1

Methotrexate

hsa04211

Longevity regulating pathway

2.72E-02

P51828, Q99941, P18848

ADCY7, CREBL1, ATF4

Methotrexate

hsa04213

Longevity regulating pathway - multiple species

3.03E-02

P51828, P0DMV8

ADCY7, HSPA1A

Methotrexate

hsa04261

Adrenergic signaling in cardiomyocytes

3.65E-04

P67936, P51828, Q8WYR1, Q99941, P18848, Q13362, P0DP24, Q13557

TPM4, ADCY7, PIK3R5, CREBL1, ATF4, PPP2R5C, CALM2, CAMK2D

Methotrexate

hsa04270

Vascular smooth muscle contraction

1.86E-02

P0DP24, P51828, P35579, P35749

CALM2, ADCY7, MYH9, MYH11

Methotrexate

hsa04330

Notch signaling pathway

2.93E-02

Q13547, Q92769, Q92830

HDAC1, HDAC2, KAT2A

Methotrexate

hsa04340

Hedgehog signaling pathway

3.32E-02

P49841, P22694

GSK3B, PRKACB

Methotrexate

hsa04371

Apelin signaling pathway

7.95E-04

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

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

Methotrexate

hsa04540

Gap junction

1.08E-02

Q13509, P68371, Q71U36, Q9NRA1

TUBB3, TUBB2C, TUBA1A, PDGFC

Methotrexate

hsa04612

Antigen processing and presentation

2.84E-02

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

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

Methotrexate

hsa04613

Neutrophil extracellular trap formation

1.38E-03

O60603, P05164, P08246, Q9UM07, Q92769, Q6FI13, Q15080, P20160, P08311, P49913, O75015, P21730, P21462, O43315, Q16539

TLR2, MPO, ELA2, PADI4, HDAC2, H2AC18; H2AC19, NCF4, AZU1, CTSG, CAMP, FCGR3B, C5AR1, FPR1, AQP9, MAPK14

Methotrexate

hsa04621

NOD-like receptor signaling pathway

3.24E-02

Q16539, Q14643, P21796, P10599, P43490, O00463, P29728, P09341, P12838

MAPK14, ITPR1, VDAC1, TXN, PBEF1, TRAF5, OAS2, CXCL1, DEFA4

Methotrexate

hsa04623

Cytosolic DNA-sensing pathway

2.59E-02

P01568, P25963

IFNA21, NFKBIA

Methotrexate

hsa04640

Hematopoietic cell lineage

8.19E-04

P13612, P14778, P27930, P15144, P11836, P25063, P07766, P09693, P01732, P13765, P01375, P09603

ITGA4, IL1R1, IL1R2, ANPEP, MS4A1, CD24, CD3E, CD3G, CD8A, HLA-DOB, TNF, CSF1

Methotrexate

hsa04650

Natural killer cell mediated cytotoxicity

1.77E-02

P78314, O60880, P20963, Q13241, P26718, O75015, P26717, P26715

SH3BP2, SH2D1A, CD247, KLRD1, KLRK1, FCGR3B, KLRC2, KLRC1

Methotrexate

hsa04657

IL-17 signaling pathway

3.31E-02

P49841, P14780, P01375

GSK3B, MMP9, TNF

Methotrexate

hsa04658

Th1 and Th2 cell differentiation

4.11E-04

Q04759, P07766, P20963, P09693, Q16539, Q14765, P23771, Q9UL17, P13765, Q13761

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

Methotrexate

hsa04659

Th17 cell differentiation

1.27E-03

P25963, Q04759, Q16539, P19174, P42224, P14784, P14778, Q9UL17, P84022, P08238, P07766, P09693, P20963

NFKBIA, PRKCQ, MAPK14, PLCG1, STAT1, IL2RB, IL1R1, TBX21, SMAD3, HSP90AB1, CD3E, CD3G, CD247

Methotrexate

hsa04660

T cell receptor signaling pathway

1.84E-05

P01375, Q9UDY8, Q04759, P10747, O95267, Q08881, P07766, P20963, P09693, P01732, Q13191, Q16539, P49841

TNF, MALT1, PRKCQ, CD28, RASGRP1, ITK, CD3E, CD247, CD3G, CD8A, CBLB, 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
Q9UM07	PADI4	Protein-arginine deiminase type-4	P01375	TNF	Tumor necrosis factor	0.788
Q9UM07	PADI4	Protein-arginine deiminase type-4	Q9UDY8	MALT1	Mucosa-associated lymphoid tissue lymphoma translocation protein 1	-0.779
P41440	SLC19A1	Reduced folate transporter	Q04759	PRKCQ	Protein kinase C theta type	-0.747
Q9UM07	PADI4	Protein-arginine deiminase type-4	Q04759	PRKCQ	Protein kinase C theta type	-0.91
Q9UM07	PADI4	Protein-arginine deiminase type-4	P10747	CD28	T-cell-specific surface glycoprotein CD28	-0.735
P41440	SLC19A1	Reduced folate transporter	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.817
Q9UM07	PADI4	Protein-arginine deiminase type-4	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.799
P41440	SLC19A1	Reduced folate transporter	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.745
Q9UM07	PADI4	Protein-arginine deiminase type-4	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.855
P41440	SLC19A1	Reduced folate transporter	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	-0.761
P41440	SLC19A1	Reduced folate transporter	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.773
Q9UM07	PADI4	Protein-arginine deiminase type-4	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.828
P41440	SLC19A1	Reduced folate transporter	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.811
Q9UM07	PADI4	Protein-arginine deiminase type-4	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.793
P41440	SLC19A1	Reduced folate transporter	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.72
Q9UM07	PADI4	Protein-arginine deiminase type-4	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.839
P41440	SLC19A1	Reduced folate transporter	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	-0.851
Q9UM07	PADI4	Protein-arginine deiminase type-4	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	-0.796
P41440	SLC19A1	Reduced folate transporter	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.8
P41440	SLC19A1	Reduced folate transporter	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.747

Methotrexate

hsa04664

Fc epsilon RI signaling pathway

4.48E-04

P04141, P07948, P19174, P09917, P20292

CSF2, LYN, PLCG1, ALOX5, ALOX5AP

Methotrexate

hsa04668

TNF signaling pathway

4.96E-02

O00463, Q13546, Q13489, Q16539, Q13077, P14780

TRAF5, RIPK1, BIRC3, MAPK14, TRAF1, MMP9

Methotrexate

hsa04672

Intestinal immune network for IgA production

1.66E-02

P10747, P13765, P13612

CD28, HLA-DOB, ITGA4

Methotrexate

hsa04713

Circadian entrainment

2.18E-02

P0DP23, P62873, P63218, P50151

CALM1, GNB1, GNG5, GNG10

Methotrexate

hsa04714

Thermogenesis

3.31E-02

P51828, P62753, P12074, O15239

ADCY7, RPS6, COX6A1, NDUFA1

Methotrexate

hsa04724

Glutamatergic synapse

1.57E-02

P62873, P63218, P50151, P15104

GNB1, GNG5, GNG10, GLUL

Methotrexate

hsa04725

Cholinergic synapse

2.17E-02

P51828, P18848, Q13557

ADCY7, ATF4, CAMK2D

Methotrexate

hsa04726

Serotonergic synapse

3.80E-02

P62873, P63218, P50151, P09917

GNB1, GNG5, GNG10, ALOX5

Methotrexate

hsa04727

GABAergic synapse

4.18E-03

P62873, P63218, P50151, P15104

GNB1, GNG5, GNG10, GLUL

Methotrexate

hsa04728

Dopaminergic synapse

4.78E-02

Q99941, P18848, Q13557

CREBL1, ATF4, CAMK2D

Methotrexate

hsa04730

Long-term depression

4.86E-02

Q14344, P07948

GNA13, LYN

Methotrexate

hsa04744

Phototransduction

9.21E-03

P62873, P0DP23

GNB1, CALM1

Methotrexate

hsa04910

Insulin signaling pathway

2.35E-02

P22694, P06737, P49841

PRKACB, PYGL, GSK3B

Methotrexate

hsa04911

Insulin secretion

4.03E-04

P51828, Q99941, P18848, Q13557

ADCY7, CREBL1, ATF4, CAMK2D

Methotrexate

hsa04912

GnRH signaling pathway

2.17E-02

P51828, P18848, Q13557

ADCY7, ATF4, CAMK2D

Methotrexate

hsa04915

Estrogen signaling pathway

1.02E-04

Q99941, P18848, P51828, P07900, P0DMV8, P11142, P0DP24, Q15788

CREBL1, ATF4, ADCY7, HSP90AA1, HSPA1A, HSPA8, CALM2, NCOA1

Methotrexate

hsa04918

Thyroid hormone synthesis

1.98E-04

P51828, Q99941, P18848, P14625, P02768

ADCY7, CREBL1, ATF4, HSP90B1, ALB

Methotrexate

hsa04919

Thyroid hormone signaling pathway

7.11E-03

P49841, P22694, O60244, Q9NVC6

GSK3B, PRKACB, MED14, MED17

Methotrexate

hsa04921

Oxytocin signaling pathway

2.92E-02

P0DP24, P51828, Q96RR4, Q8WYR1

CALM2, ADCY7, CAMKK2, PIK3R5

Methotrexate

hsa04924

Renin secretion

3.64E-02

P22694, P07550, Q14643

PRKACB, ADRB2, ITPR1

Methotrexate

hsa04925

Aldosterone synthesis and secretion

1.69E-03

Q99941, P18848, P51828, Q13557

CREBL1, ATF4, ADCY7, CAMK2D

Methotrexate

hsa04926

Relaxin signaling pathway

3.34E-02

Q99941, P18848, P51828

CREBL1, ATF4, ADCY7

Methotrexate

hsa04927

Cortisol synthesis and secretion

6.33E-04

Q14643, Q99941, P18848, P51828, P22694

ITPR1, CREBL1, ATF4, ADCY7, PRKACB

Methotrexate

hsa04928

Parathyroid hormone synthesis, secretion and action

2.17E-02

P51828, Q99941, P18848

ADCY7, CREBL1, ATF4

Methotrexate

hsa04931

Insulin resistance

1.94E-02

P01375, P49841, P06737

TNF, GSK3B, PYGL

Methotrexate

hsa04934

Cushing syndrome

1.12E-03

Q99941, P18848, P51828, Q13557

CREBL1, ATF4, ADCY7, CAMK2D

Methotrexate

hsa04935

Growth hormone synthesis, secretion and action

2.72E-02

P51828, Q99941, P18848

ADCY7, CREBL1, ATF4

Methotrexate

hsa04940

Type I diabetes mellitus

3.64E-02

P10747, P13765, P01375

CD28, HLA-DOB, TNF

Methotrexate

hsa04962

Vasopressin-regulated water reabsorption

2.18E-02

P52566, P62491

ARHGDIB, RAB11A

Methotrexate

hsa04970

Salivary secretion

4.92E-02

P07550, P22694, Q14643, P49913

ADRB2, PRKACB, ITPR1, CAMP

Methotrexate

hsa04976

Bile secretion

2.44E-02

P22694, P08183

PRKACB, ABCB1

Methotrexate

hsa05012

Parkinson disease

1.77E-02

P60604, P19174, P0DP23, Q71U36, Q13509, P68371

UBE2G2, PLCG1, CALM1, TUBA1A, TUBB3, TUBB2C

Methotrexate

hsa05030

Cocaine addiction

4.87E-02

Q99941, P18848

CREBL1, ATF4

Methotrexate

hsa05031

Amphetamine addiction

6.41E-03

Q13557, Q99941, P18848

CAMK2D, CREBL1, ATF4

Methotrexate

hsa05032

Morphine addiction

2.18E-02

P62873, P63218, P50151, Q13370

GNB1, GNG5, GNG10, PDE3B

Methotrexate

hsa05034

Alcoholism

2.79E-02

P62879, Q9BTM1

GNB2, H2AFJ

Methotrexate

hsa05120

Epithelial cell signaling in Helicobacter pylori infection

3.32E-04

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

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

Methotrexate

hsa05130

Pathogenic Escherichia coli infection

3.19E-02

Q71U36, P16333, Q13509, P68371, Q14344, P25963

TUBA1A, NCK1, TUBB3, TUBB2C, GNA13, NFKBIA

Methotrexate

hsa05132

Salmonella infection

2.75E-02

P25963, P08238, O75369, Q71U36, Q13509, P68371, P49754

NFKBIA, HSP90AB1, FLNB, TUBA1A, TUBB3, TUBB2C, VPS41

Methotrexate

hsa05134

Legionellosis

4.75E-02

P25963, P11215, P11142

NFKBIA, ITGAM, HSPA8

Methotrexate

hsa05140

Leishmaniasis

4.82E-02

P14598, P11215, P42224, P25963

NCF1, ITGAM, STAT1, NFKBIA

Methotrexate

hsa05144

Malaria

4.92E-02

O60603, P01375, P35443, P26718

TLR2, TNF, THBS4, KLRK1

Methotrexate

hsa05145

Toxoplasmosis

3.55E-02

P23458, Q8WYR1, P0DMV8

JAK1, PIK3R5, HSPA1A

Methotrexate

hsa05146

Amoebiasis

1.48E-02

P09341, P27930, P01375, O60603, P05089, P22694, P08311

CXCL1, IL1R2, TNF, TLR2, ARG1, PRKACB, CTSG

Methotrexate

hsa05161

Hepatitis B

3.34E-02

Q99941, P18848, P27348

CREBL1, ATF4, YWHAQ

Methotrexate

hsa05163

Human cytomegalovirus infection

1.79E-04

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

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

Methotrexate

hsa05167

Kaposi sarcoma-associated herpesvirus infection

4.85E-05

P01568, P42224, P25963, P49841, P62873, P63218, P50151, P09341, P19174, Q14643, O15123, P07948, Q16539, P04141, P0DP23

IFNA21, STAT1, NFKBIA, GSK3B, GNB1, GNG5, GNG10, CXCL1, PLCG1, ITPR1, ANGPT2, LYN, MAPK14, CSF2, CALM1

Methotrexate

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

Methotrexate

hsa05169

Epstein-Barr virus infection

1.24E-03

Q13547, Q92769, O00463, Q16539, P07948, P30101, Q13761, P24522, P30279, P29728, P07766, P09693, P20963

HDAC1, HDAC2, TRAF5, MAPK14, LYN, PDIA3, RUNX3, GADD45A, CCND2, OAS2, CD3E, CD3G, CD247

Methotrexate

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

Methotrexate

hsa05171

Coronavirus disease - COVID-19

4.36E-05

P23396, P62753, P62249, P62906, P27635, Q07020, P46776, P61513

RPS3, RPS6, RPS16, RPL10A, RPL10, RPL18, RPL27A, RPL37A

Methotrexate

hsa05200

Pathways in cancer

2.14E-04

P17301, P08238, P42224, P25963, P19174, P43246, P84022, P20585, P62873, P62879, P63218, P50151, Q14344, O75293, P0DP23, P01568, P14784

ITGA2, HSP90AB1, STAT1, NFKBIA, PLCG1, MSH2, SMAD3, MSH3, GNB1, GNB2, GNG5, GNG10, GNA13, GADD45B, CALM1, IFNA21, IL2RB

Methotrexate

hsa05202

Transcriptional misregulation in cancer

2.85E-04

Q15532, P41732, P14780, P27930, Q15744, Q16548, Q13489, Q13077, P35226, P05164, P12838, P08246, Q9C0K0, Q92769, P12980, P24522

SS18, TSPAN7, MMP9, IL1R2, CEBPE, BCL2A1, BIRC3, TRAF1, BMI1, MPO, DEFA4, ELA2, BCL11B, 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
P09958	FURIN	Furin	Q15532	SS18	Protein SSXT	-0.749
P09958	FURIN	Furin	P41732	TSPAN7	Tetraspanin-7	0.719
Q9UM07	PADI4	Protein-arginine deiminase type-4	P14780	MMP9	Matrix metalloproteinase-9	0.9
P09958	FURIN	Furin	P14780	MMP9	Matrix metalloproteinase-9	0.843
Q9UM07	PADI4	Protein-arginine deiminase type-4	P27930	IL1R2	Interleukin-1 receptor type 2	0.721
P09958	FURIN	Furin	P27930	IL1R2	Interleukin-1 receptor type 2	0.763
Q9UM07	PADI4	Protein-arginine deiminase type-4	Q15744	CEBPE	CCAAT/enhancer-binding protein epsilon	0.772
Q9UM07	PADI4	Protein-arginine deiminase type-4	Q16548	BCL2A1	Bcl-2-related protein A1	0.776
P09958	FURIN	Furin	Q16548	BCL2A1	Bcl-2-related protein A1	0.793
P09958	FURIN	Furin	Q13489	BIRC3	Baculoviral IAP repeat-containing protein 3	-0.714
P09958	FURIN	Furin	Q13077	TRAF1	TNF receptor-associated factor 1	-0.741
Q9UM07	PADI4	Protein-arginine deiminase type-4	P35226	BMI1	Polycomb complex protein BMI-1	-0.716
P09958	FURIN	Furin	P35226	BMI1	Polycomb complex protein BMI-1	-0.742
Q9UM07	PADI4	Protein-arginine deiminase type-4	P35226	BMI1	Polycomb complex protein BMI-1	-0.716
P09958	FURIN	Furin	P35226	BMI1	Polycomb complex protein BMI-1	-0.742
Q9UM07	PADI4	Protein-arginine deiminase type-4	P05164	MPO	Myeloperoxidase	0.909
P09958	FURIN	Furin	P05164	MPO	Myeloperoxidase	0.708
Q9UM07	PADI4	Protein-arginine deiminase type-4	P12838	DEFA4	Neutrophil defensin 4	0.882
Q9UM07	PADI4	Protein-arginine deiminase type-4	P08246	ELA2	Neutrophil elastase	0.889
P09958	FURIN	Furin	P08246	ELA2	Neutrophil elastase	0.757
Q9UM07	PADI4	Protein-arginine deiminase type-4	Q9C0K0	BCL11B	B-cell lymphoma/leukemia 11B	-0.85
P09958	FURIN	Furin	Q9C0K0	BCL11B	B-cell lymphoma/leukemia 11B	-0.811
P09958	FURIN	Furin	Q92769	HDAC2	Histone deacetylase 2	-0.798
Q9UM07	PADI4	Protein-arginine deiminase type-4	P12980	LYL1	Protein lyl-1	0.702
Q9UM07	PADI4	Protein-arginine deiminase type-4	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.859
P09958	FURIN	Furin	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.806

Methotrexate

hsa05203

Viral carcinogenesis

1.46E-02

Q99941, P18848, P27348, P61978

CREBL1, ATF4, YWHAQ, HNRPK

Methotrexate

hsa05212

Pancreatic cancer

4.75E-02

P42224, P84022, O75293

STAT1, SMAD3, GADD45B

Methotrexate

hsa05214

Glioma

4.75E-02

P0DP23, P19174, O75293

CALM1, PLCG1, GADD45B

Methotrexate

hsa05215

Prostate cancer

4.48E-02

P18848, P14625

ATF4, HSP90B1

Methotrexate

hsa05217

Basal cell carcinoma

2.01E-02

Q13635, P04628, Q9UJU2, P24522

PTCH1, WNT1, LEF1, GADD45A

Methotrexate

hsa05230

Central carbon metabolism in cancer

1.12E-02

P11413

G6PD

Methotrexate

hsa05235

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

3.65E-02

O95267, P07766, P20963, P09693, Q04759, Q16539

RASGRP1, CD3E, CD247, CD3G, PRKCQ, MAPK14

Methotrexate

hsa05310

Asthma

1.66E-02

P13765, P12724, P01375

HLA-DOB, RNASE3, TNF

Methotrexate

hsa05321

Inflammatory bowel disease

1.14E-03

O60603, P01375, P13765, Q14765, Q9UL17, P23771

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

Methotrexate

hsa05323

Rheumatoid arthritis

1.58E-02

P01375, P13765, P10747, P09341, O60603

TNF, HLA-DOB, CD28, CXCL1, TLR2

Methotrexate

hsa05332

Graft-versus-host disease

2.03E-03

P13765, P10747, P01375, P26715, Q13241

HLA-DOB, CD28, TNF, KLRC1, KLRD1

Methotrexate

hsa05415

Diabetic cardiomyopathy

3.59E-02

P11413

G6PD

Community members of Methotrexate (S_DC: 3.33)

UniProtAC

Gene Name

Protein Name

Reported/
Predicted

S_PV

DHFR

Dihydrofolate reductase

Reported

0.338

0.1868

0.2263

0.7688

P04818

TYMS

Thymidylate synthase

Reported

0.4553

0.2706

0.1893

0.9582

Q15788

NCOA1

Nuclear receptor coactivator 1

Predicted

0.4368

0.0828

0.3114

0.6954

P52209

PGD

6Nonephosphogluconate dehydrogenase, decarboxylating

Predicted

0.195

0.1454

0.2642

0.6525

P11413

G6PD

GlucoseNone6Nonephosphate 1Nonedehydrogenase

Predicted

0.4435

0.6369

0.2929

1.7884

P41440

SLC19A1

Reduced folate transporter

Predicted

0.1425

0.038

0.0985

0.2457

Q9UM07

PADI4

ProteinNonearginine deiminase typeNone4

Predicted

0.1488

0.2778

0.4267

1.0567

Q99707

MTR

Methionine synthase

Predicted

0.1612

0.0562

0.195

0.3881

P08183

ABCB1

ATPNonedependent translocase ABCB1

Predicted

0.0788

0.2052

2.2446

P08238

HSP90AB1

Heat shock protein HSP 90Nonebeta

Predicted

0.0611

0.5208

0.741

1.8131

P14625

HSP90B1

Endoplasmin

Predicted

0.2336

0.1497

0.5384

0.9546

P07900

HSP90AA1

Heat shock protein HSP 90Nonealpha

Predicted

0.4727

0.6064

0.741

2.1901

P31939

ATIC

Bifunctional purine biosynthesis protein ATIC

Reported

P09958

FURIN

Furin

Predicted

0.1569

0.075

0.2286

Gene name	UniProt_ID	Bioactivity	Value (nM)
DHFR	P00374	IC50	0.6
DHFR	P00374	IC50	0.7
DHFR	P00374	IC50	0.72
DHFR	P00374	Ki	0.00034
DHFR	P00374	Ki	0.0012
DHFR	P00374	Ki	0.01
DHFR	P00374	Kd	0.194984
TYMS	P04818	IC50	10
TYMS	P04818	IC50	3600
TYMS	P04818	IC50	29000
TYMS	P04818	Ki	600

PharmaCoNets of Methotrexate (SPCN: 61.12 )

Methotrexate regulated-network (SDN: 18.36)

Community members of Methotrexate (SDC: 3.33)

PharmaCoNets of Methotrexate (S_PCN: 61.12 )

Methotrexate regulated-network (S_DN: 18.36)

Community members of Methotrexate (S_DC: 3.33)