PharmaCoNets

PharmaCoNets of Tibolone (S_PCN: 145.43 )

Tibolone regulated-network (S_DN: 19.71)

Drug Name

Pathway ID

Pathway name

P-value

No. of gene members

UniProt AC

Gene name

Detail of Coexpression

Tibolone

hsa00020

Citrate cycle (TCA cycle)

3.41E-02

P50213, O14521

IDH3A, SDHD

Tibolone

hsa00030

Pentose phosphate pathway

8.97E-03

P11413

G6PD

Tibolone

hsa00052

Galactose metabolism

1.03E-02

P06280, O43451

GLA, MGAM

Tibolone

hsa00053

Ascorbate and aldarate metabolism

4.93E-02

P14550

AKR1A1

Tibolone

hsa00071

Fatty acid degradation

3.77E-02

O75521, P11766, P33121

ECI2, ADH5, ACSL1

Tibolone

hsa00190

Oxidative phosphorylation

4.36E-03

Q16718, Q13488, O14521

NDUFA5, TCIRG1, SDHD

Tibolone

hsa00220

Arginine biosynthesis

4.88E-02

P49448

GLUD2

Tibolone

hsa00250

Alanine, aspartate and glutamate metabolism

4.88E-02

P49448

GLUD2

Tibolone

hsa00471

D-Glutamine and D-glutamate metabolism

1.65E-02

P49448

GLUD2

Tibolone

hsa00480

Glutathione metabolism

1.35E-02

P11413

G6PD

Tibolone

hsa00500

Starch and sucrose metabolism

1.00E-03

O43451, P46976, P06737

MGAM, GYG1, PYGL

Tibolone

hsa00512

Mucin type O-glycan biosynthesis

3.78E-02

O95395, Q8N4A0

GCNT3, GALNT4

Tibolone

hsa00533

Glycosaminoglycan biosynthesis - keratan sulfate

3.43E-02

Q9NY97

B3GNT2

Tibolone

hsa00565

Ether lipid metabolism

4.93E-02

Q8N661

TMEM86B

Tibolone

hsa00590

Arachidonic acid metabolism

3.85E-02

P11712, P09960

CYP2C9, LTA4H

Tibolone

hsa00591

Linoleic acid metabolism

4.07E-02

P11712

CYP2C9

Tibolone

hsa00600

Sphingolipid metabolism

3.76E-02

P15289

ARSA

Tibolone

hsa00630

Glyoxylate and dicarboxylate metabolism

1.88E-05

P40925, P15104

MDH1, GLUL

Tibolone

hsa00730

Thiamine metabolism

5.29E-03

P05186, P24666

ALPL, ACP1

Tibolone

hsa00770

Pantothenate and CoA biosynthesis

1.15E-02

O95498, Q9NRN7

VNN2, AASDHPPT

Tibolone

hsa00910

Nitrogen metabolism

4.88E-02

P49448

GLUD2

Tibolone

hsa00920

Sulfur metabolism

3.18E-02

Q16762

TST

Tibolone

hsa00970

Aminoacyl-tRNA biosynthesis

2.35E-05

O95363, P54136, P14868, Q15046

FARS2, RARS1, DARS, KARS

Tibolone

hsa00980

Metabolism of xenobiotics by cytochrome P450

9.14E-03

P78417, P11712

GSTO1, CYP2C9

Tibolone

hsa00982

Drug metabolism - cytochrome P450

9.14E-03

P11712, P78417

CYP2C9, GSTO1

Tibolone

hsa00983

Drug metabolism - other enzymes

2.44E-02

P32320, P05164

CDA, MPO

Tibolone

hsa01200

Carbon metabolism

2.91E-02

P11413

G6PD

Tibolone

hsa01210

2-Oxocarboxylic acid metabolism

3.43E-02

P50213

IDH3A

Tibolone

hsa01230

Biosynthesis of amino acids

3.91E-02

P51854, Q99707, P50213

TKTL1, MTR, IDH3A

Tibolone

hsa01521

EGFR tyrosine kinase inhibitor resistance

1.82E-02

P08069

IGF1R

Tibolone

hsa01522

Endocrine resistance

2.16E-02

P08069

IGF1R

Tibolone

hsa01523

Antifolate resistance

3.80E-02

Q92820, P04818

GGH, TYMS

Tibolone

hsa02010

ABC transporters

4.93E-02

Q8IZY2

ABCA7

Tibolone

hsa03008

Ribosome biogenesis in eukaryotes

4.94E-02

P19784, P67870

CSNK2A2, CSNK2B

Tibolone

hsa03040

Spliceosome

4.48E-08

Q14562, O43143, O60508, P08579, P26368, Q13595, Q07955, Q01130, P84103, Q13243, P11142, Q9Y2W2, O43447, O75643

DHX8, DHX15, CDC40, SNRPB2, U2AF2, TRA2A, SFRS1, SFRS2, SFRS3, SFRS5, HSPA8, WBP11, PPIH, ASCC3L1

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
P29375	JARID1A	Lysine-specific demethylase 5A	Q14562	DHX8	ATP-dependent RNA helicase DHX8	0.781
P29375	JARID1A	Lysine-specific demethylase 5A	O43143	DHX15	ATP-dependent RNA helicase DHX15	0.794
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O43143	DHX15	ATP-dependent RNA helicase DHX15	-0.76
P35610	SOAT1	Sterol O-acyltransferase 1	O60508	CDC40	Pre-mRNA-processing factor 17	0.76
P29375	JARID1A	Lysine-specific demethylase 5A	O60508	CDC40	Pre-mRNA-processing factor 17	0.875
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O60508	CDC40	Pre-mRNA-processing factor 17	-0.812
P35610	SOAT1	Sterol O-acyltransferase 1	P08579	SNRPB2	U2 small nuclear ribonucleoprotein B''	0.787
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P08579	SNRPB2	U2 small nuclear ribonucleoprotein B''	-0.822
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P26368	U2AF2	Splicing factor U2AF 65 kDa subunit	-0.751
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13595	TRA2A	Transformer-2 protein homolog alpha	-0.74
P35610	SOAT1	Sterol O-acyltransferase 1	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	0.712
P29375	JARID1A	Lysine-specific demethylase 5A	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	0.725
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q07955	SFRS1	Serine/arginine-rich splicing factor 1	-0.749
P35610	SOAT1	Sterol O-acyltransferase 1	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	0.822
P29375	JARID1A	Lysine-specific demethylase 5A	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	0.862
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q01130	SFRS2	Serine/arginine-rich splicing factor 2	-0.798
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P84103	SFRS3	Serine/arginine-rich splicing factor 3	-0.773
P29375	JARID1A	Lysine-specific demethylase 5A	Q13243	SFRS5	Serine/arginine-rich splicing factor 5	0.732
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13243	SFRS5	Serine/arginine-rich splicing factor 5	-0.822
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P11142	HSPA8	Heat shock cognate 71 kDa protein	-0.802
P35610	SOAT1	Sterol O-acyltransferase 1	Q9Y2W2	WBP11	WW domain-binding protein 11	0.711
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q9Y2W2	WBP11	WW domain-binding protein 11	-0.743
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O43447	PPIH	Peptidyl-prolyl cis-trans isomerase H	-0.766
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O75643	ASCC3L1	U5 small nuclear ribonucleoprotein 200 kDa helicase	-0.745

Tibolone

hsa03060

Protein export

3.28E-02

Q15070

OXA1L

Tibolone

hsa03430

Mismatch repair

4.38E-02

P20585

MSH3

Tibolone

hsa03450

Non-homologous end-joining

4.21E-02

P13010

XRCC5

Tibolone

hsa04010

MAPK signaling pathway

4.15E-02

P08069

IGF1R

Tibolone

hsa04014

Ras signaling pathway

9.55E-04

P42338, P20827, P49767, P08069, Q13009, Q7LDG7, P63218, P50151, P19174

PIK3CB, EFNA1, VEGFC, IGF1R, TIAM1, RASGRP2, GNG5, GNG10, PLCG1

Tibolone

hsa04015

Rap1 signaling pathway

9.79E-05

P20827, P49767, P08069, P06213, Q96FS4, P11215, P25116, Q8TEU7, Q13009, O00522, Q7LDG7, P42338, P08514, P19174

EFNA1, VEGFC, IGF1R, INSR, SIPA1, ITGAM, F2R, RAPGEF6, TIAM1, KRIT1, RASGRP2, PIK3CB, ITGA2B, PLCG1

Tibolone

hsa04024

cAMP signaling pathway

4.25E-03

P63092, P42338, P26678, P0DP23, P61586, Q13370, Q13009

GNAS, PIK3CB, PLN, CALM1, RHOA, PDE3B, TIAM1

Tibolone

hsa04062

Chemokine signaling pathway

9.23E-03

P09769, P07948, P42338, P19174, P63218, P50151, P43250, Q7LDG7, Q13009, Q8WYR1

FGR, LYN, PIK3CB, PLCG1, GNG5, GNG10, GRK6, RASGRP2, TIAM1, PIK3R5

Tibolone

hsa04064

NF-kappa B signaling pathway

4.58E-03

Q13489, Q13546, Q9UDY8, Q9UNE0

BIRC3, RIPK1, MALT1, EDAR

Tibolone

hsa04066

HIF-1 signaling pathway

2.16E-02

P08069

IGF1R

Tibolone

hsa04068

FoxO signaling pathway

1.99E-02

P08069

IGF1R

Tibolone

hsa04070

Phosphatidylinositol signaling system

4.86E-02

P0DP23, P42338, P27987

CALM1, PIK3CB, ITPKB

Tibolone

hsa04071

Sphingolipid signaling pathway

1.94E-02

Q9H228, P01375, Q9UQC2

EDG8, TNF, GAB2

Tibolone

hsa04072

Phospholipase D signaling pathway

2.75E-02

P61586, O14986, P63092

RHOA, PIP5K1B, GNAS

Tibolone

hsa04080

Neuroactive ligand-receptor interaction

3.70E-02

P08311, P48058, Q15722, Q9H228, P43657, P21730, P35318

CTSG, GRIA4, LTB4R, EDG8, P2RY5, C5AR1, ADM

Tibolone

hsa04110

Cell cycle

6.80E-03

P06493, O75293, P30304, P33981, P42773, P01106

CDK1, GADD45B, CDC25A, TTK, CDKN2C, MYC

Tibolone

hsa04114

Oocyte meiosis

3.19E-03

P51812, Q02750, P16298, Q17RY0, P08069

RPS6KA3, MAP2K1, PPP3CB, CPEB4, IGF1R

Tibolone

hsa04120

Ubiquitin mediated proteolysis

3.44E-02

Q14145, Q13042, P62837, Q15751

KEAP1, CDC16, UBE2D2, HERC1

Tibolone

hsa04122

Sulfur relay system

3.18E-02

Q16762

TST

Tibolone

hsa04137

Mitophagy - animal

2.52E-02

P19784, P67870

CSNK2A2, CSNK2B

Tibolone

hsa04140

Autophagy - animal

2.82E-02

P08069

IGF1R

Tibolone

hsa04141

Protein processing in endoplasmic reticulum

2.78E-02

P07384, O95487, O95816

CAPN1, SEC24B, BAG2

Tibolone

hsa04150

mTOR signaling pathway

7.74E-03

P08069, Q02750, Q9NQL2, P51812

IGF1R, MAP2K1, RRAGD, RPS6KA3

Tibolone

hsa04151

PI3K-Akt signaling pathway

1.89E-03

P42338, P43657, P20827, P49767, P08238, Q8WYR1, P63218, P50151, O15335, Q13751, P14784, P30281

PIK3CB, P2RY5, EFNA1, VEGFC, HSP90AB1, PIK3R5, GNG5, GNG10, CHAD, LAMB3, IL2RB, CCND3

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
P35610	SOAT1	Sterol O-acyltransferase 1	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.813
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	0.777
P35610	SOAT1	Sterol O-acyltransferase 1	P43657	P2RY5	Lysophosphatidic acid receptor 6	0.784
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P43657	P2RY5	Lysophosphatidic acid receptor 6	-0.735
P35610	SOAT1	Sterol O-acyltransferase 1	P20827	EFNA1	Ephrin-A1	-0.763
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P20827	EFNA1	Ephrin-A1	0.715
P35610	SOAT1	Sterol O-acyltransferase 1	P49767	VEGFC	Vascular endothelial growth factor C	-0.711
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P49767	VEGFC	Vascular endothelial growth factor C	0.743
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P08238	HSP90AB1	Heat shock protein HSP 90-beta	-0.823
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q8WYR1	PIK3R5	Phosphoinositide 3-kinase regulatory subunit 5	0.752
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	0.941
P35610	SOAT1	Sterol O-acyltransferase 1	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	-0.838
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	0.948
P35610	SOAT1	Sterol O-acyltransferase 1	O15335	CHAD	Chondroadherin	-0.792
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O15335	CHAD	Chondroadherin	0.795
P35610	SOAT1	Sterol O-acyltransferase 1	Q13751	LAMB3	Laminin subunit beta-3	-0.805
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13751	LAMB3	Laminin subunit beta-3	0.844
P35610	SOAT1	Sterol O-acyltransferase 1	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.779
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P14784	IL2RB	Interleukin-2 receptor subunit beta	-0.835
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P30281	CCND3	G1/S-specific cyclin-D3	0.743

Tibolone

hsa04152

AMPK signaling pathway

2.07E-03

P08069, Q96EB6, P36956

IGF1R, SIRT1, SREBF1

Tibolone

hsa04210

Apoptosis

3.58E-02

O76075, P01375, Q9NR28, Q16548

DFFB, TNF, DIABLO, BCL2A1

Tibolone

hsa04211

Longevity regulating pathway

1.34E-03

Q12778, P08069, Q9UEF7, Q96KQ7

FOXO1, IGF1R, KL, EHMT2

Tibolone

hsa04213

Longevity regulating pathway - multiple species

2.83E-03

P08069, Q9Y4H2, Q13547

IGF1R, IRS2, HDAC1

Tibolone

hsa04215

Apoptosis - multiple species

1.56E-02

Q13489, P10415

BIRC3, BCL2

Tibolone

hsa04217

Necroptosis

1.85E-03

P01375, P01568, P48023, Q13489, Q13546, Q14765, Q99878

TNF, IFNA21, FASLG, BIRC3, RIPK1, STAT4, H2AC14

Tibolone

hsa04218

Cellular senescence

4.79E-02

P01106, O75293, P30304, P06493

MYC, GADD45B, CDC25A, CDK1

Tibolone

hsa04310

Wnt signaling pathway

4.17E-03

P61586, P19784, P67870

RHOA, CSNK2A2, CSNK2B

Tibolone

hsa04340

Hedgehog signaling pathway

3.32E-02

P49841, P22694

GSK3B, PRKACB

Tibolone

hsa04360

Axon guidance

1.58E-04

P16333, P20827, O95631, P42338, P07332, P23528, P19174, Q06124

NCK1, EFNA1, NTN1, PIK3CB, FES, CFL1, PLCG1, PTPN11

Tibolone

hsa04370

VEGF signaling pathway

2.68E-03

P16298, Q05397, Q02750

PPP3CB, PTK2, MAP2K1

Tibolone

hsa04371

Apelin signaling pathway

1.00E-02

P63218, P50151, Q8WYR1, Q14814, Q14344, Q13485, P84022

GNG5, GNG10, PIK3R5, MEF2D, GNA13, SMAD4, SMAD3

Tibolone

hsa04390

Hippo signaling pathway

2.08E-02

P84022, Q13485, Q13489

SMAD3, SMAD4, BIRC3

Tibolone

hsa04510

Focal adhesion

8.84E-03

O14986, P61586, Q16363, P08069

PIP5K1B, RHOA, LAMA4, IGF1R

Tibolone

hsa04512

ECM-receptor interaction

3.73E-02

P07359, P08514

GP1BA, ITGA2B

Tibolone

hsa04514

Cell adhesion molecules

8.19E-03

P16109, P56750, O00501

SELP, CLDN17, CLDN5

Tibolone

hsa04520

Adherens junction

1.65E-05

P08069, P19784, P67870, P61586

IGF1R, CSNK2A2, CSNK2B, RHOA

Tibolone

hsa04530

Tight junction

1.64E-06

Q8TEU7, P63261, P16989, P56750, O00501, Q9Y478, Q92974, Q14247

RAPGEF6, ACTG1, CSDA, CLDN17, CLDN5, PRKAB1, ARHGEF2, CTTN

Tibolone

hsa04550

Signaling pathways regulating pluripotency of stem cells

1.99E-02

P08069

IGF1R

Tibolone

hsa04610

Complement and coagulation cascades

1.03E-03

P25116, P09871, P0C0L4

F2R, C1S, C4A

Tibolone

hsa04611

Platelet activation

5.18E-05

P25116, P08514, Q15746, Q8WYR1, P07359

F2R, ITGA2B, MYLK, PIK3R5, GP1BA

Tibolone

hsa04613

Neutrophil extracellular trap formation

1.07E-05

P16109, P11215, Q13547, Q93077, P58876, P62807, Q16778, O60814, P68431, P08514, P07359

SELP, ITGAM, HDAC1, HIST1H2AC, H2BC5, HIST1H2BC, HIST2H2BE, H2BC12, H3C1; H3C2; H3C3; H3C4; H3C6; H3C7; H3C8; H3C10; H3C11; H3C12, ITGA2B, GP1BA

Tibolone

hsa04620

Toll-like receptor signaling pathway

4.16E-02

Q13546, P01568

RIPK1, IFNA21

Tibolone

hsa04621

NOD-like receptor signaling pathway

4.72E-02

P01568, Q13489, Q13546

IFNA21, BIRC3, RIPK1

Tibolone

hsa04622

RIG-I-like receptor signaling pathway

2.39E-02

P01568, Q13546

IFNA21, RIPK1

Tibolone

hsa04623

Cytosolic DNA-sensing pathway

2.20E-03

P01568, Q13546

IFNA21, RIPK1

Tibolone

hsa04640

Hematopoietic cell lineage

1.37E-03

P13612, P21926, P14778, P27930, P15144, P07766, P09693, P01732, P01730, P09564

ITGA4, CD9, IL1R1, IL1R2, ANPEP, CD3E, CD3G, CD8A, CD4, CD7

Tibolone

hsa04650

Natural killer cell mediated cytotoxicity

9.90E-05

P16298, P50591, P78314, P06239, O60880, P20963, Q02750, Q13241, P26718, O75015, P26717, P26715

PPP3CB, TNFSF10, SH3BP2, LCK, SH2D1A, CD247, MAP2K1, KLRD1, KLRK1, FCGR3B, KLRC2, KLRC1

Tibolone

hsa04657

IL-17 signaling pathway

3.31E-02

P49841, P14780, P01375

GSK3B, MMP9, TNF

Tibolone

hsa04658

Th1 and Th2 cell differentiation

1.27E-04

Q04759, P07766, P20963, P09693, Q16539, P01730, P06239, P23771, Q9UL17

PRKCQ, CD3E, CD247, CD3G, MAPK14, CD4, LCK, GATA3, TBX21

Tibolone

hsa04659

Th17 cell differentiation

3.35E-07

P25963, Q04759, Q16539, P19174, P01730, P06239, P42224, P14784, P14778, P40189, Q9UL17, P23771, P84022, Q13485, P08238, P07766, P09693, P20963

NFKBIA, PRKCQ, MAPK14, PLCG1, CD4, LCK, STAT1, IL2RB, IL1R1, IL6ST, TBX21, GATA3, SMAD3, SMAD4, 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
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	P25963	NFKBIA	NF-kappa-B inhibitor alpha	-0.728
O43451	MGAM	Maltase-glucoamylase	Q04759	PRKCQ	Protein kinase C theta type	-0.777
O43451	MGAM	Maltase-glucoamylase	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.871
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	-0.766
O43451	MGAM	Maltase-glucoamylase	P01730	CD4	T-cell surface glycoprotein CD4	-0.724
O43451	MGAM	Maltase-glucoamylase	P06239	LCK	Tyrosine-protein kinase Lck	-0.748
P29375	JARID1A	Lysine-specific demethylase 5A	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.764
P29375	JARID1A	Lysine-specific demethylase 5A	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.768
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P14784	IL2RB	Interleukin-2 receptor subunit beta	-0.835
O43451	MGAM	Maltase-glucoamylase	P14778	IL1R1	Interleukin-1 receptor type 1	0.924
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P14778	IL1R1	Interleukin-1 receptor type 1	0.764
P29375	JARID1A	Lysine-specific demethylase 5A	P40189	IL6ST	Interleukin-6 receptor subunit beta	0.83
O43451	MGAM	Maltase-glucoamylase	Q9UL17	TBX21	T-box transcription factor TBX21	-0.799
O43451	MGAM	Maltase-glucoamylase	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.771
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	P84022	SMAD3	Mothers against decapentaplegic homolog 3	0.769
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P84022	SMAD3	Mothers against decapentaplegic homolog 3	0.725
O75469	NR1I2	Nuclear receptor subfamily 1 group I member 2	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	-0.721
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	-0.746
P29375	JARID1A	Lysine-specific demethylase 5A	P08238	HSP90AB1	Heat shock protein HSP 90-beta	0.711
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P08238	HSP90AB1	Heat shock protein HSP 90-beta	-0.823
O43451	MGAM	Maltase-glucoamylase	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	-0.73
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	-0.838
O43451	MGAM	Maltase-glucoamylase	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.755
O43451	MGAM	Maltase-glucoamylase	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.79

Tibolone

hsa04660

T cell receptor signaling pathway

6.29E-04

Q04759, P07766, P20963, P09693, P01730, P01732, Q13191, P06239, Q16539, P49841

PRKCQ, CD3E, CD247, CD3G, CD4, CD8A, CBLB, LCK, MAPK14, GSK3B

Tibolone

hsa04662

B cell receptor signaling pathway

9.03E-05

P42338, P60033, P07948, P21854, Q8N149

PIK3CB, CD81, LYN, CD72, LILRA2

Tibolone

hsa04664

Fc epsilon RI signaling pathway

1.29E-03

P42338, P07948, P19174, P09917

PIK3CB, LYN, PLCG1, ALOX5

Tibolone

hsa04666

Fc gamma R-mediated phagocytosis

3.08E-02

P42338, P23528, P14598

PIK3CB, CFL1, NCF1

Tibolone

hsa04713

Circadian entrainment

4.94E-02

P62873, P63092

GNB1, GNAS

Tibolone

hsa04714

Thermogenesis

1.25E-02

P15336, P63261, Q9Y478

ATF2, ACTG1, PRKAB1

Tibolone

hsa04720

Long-term potentiation

1.38E-02

P16298, P51812, Q02750

PPP3CB, RPS6KA3, MAP2K1

Tibolone

hsa04721

Synaptic vesicle cycle

1.80E-02

Q13488, P31645

TCIRG1, SLC6A4

Tibolone

hsa04722

Neurotrophin signaling pathway

3.27E-02

P49841, O43524, P48023

GSK3B, FOXO3, FASLG

Tibolone

hsa04723

Retrograde endocannabinoid signaling

4.94E-02

P48169, P62873

GABRA4, GNB1

Tibolone

hsa04724

Glutamatergic synapse

2.85E-03

P43003, P63092, P62873, P50151, P15104

SLC1A3, GNAS, GNB1, GNG10, GLUL

Tibolone

hsa04726

Serotonergic synapse

2.52E-02

P63092, P62873

GNAS, GNB1

Tibolone

hsa04730

Long-term depression

1.16E-02

P08069

IGF1R

Tibolone

hsa04810

Regulation of actin cytoskeleton

2.58E-02

Q15746, P08514, P25116

MYLK, ITGA2B, F2R

Tibolone

hsa04910

Insulin signaling pathway

2.35E-02

P22694, P06737, P49841

PRKACB, PYGL, GSK3B

Tibolone

hsa04913

Ovarian steroidogenesis

8.40E-04

P06213, P08069

INSR, IGF1R

Tibolone

hsa04914

Progesterone-mediated oocyte maturation

9.67E-04

P08069, Q17RY0, P42338, Q13370, P08238, P51812, Q02750

IGF1R, CPEB4, PIK3CB, PDE3B, HSP90AB1, RPS6KA3, MAP2K1

Tibolone

hsa04919

Thyroid hormone signaling pathway

7.11E-03

P49841, P22694, O60244, Q9NVC6

GSK3B, PRKACB, MED14, MED17

Tibolone

hsa04920

Adipocytokine signaling pathway

2.80E-02

Q06124, Q9Y478

PTPN11, PRKAB1

Tibolone

hsa04923

Regulation of lipolysis in adipocytes

3.76E-02

P06213

INSR

Tibolone

hsa04924

Renin secretion

3.77E-02

Q13370, P0DP23

PDE3B, CALM1

Tibolone

hsa04930

Type II diabetes mellitus

3.14E-02

P06213

INSR

Tibolone

hsa04931

Insulin resistance

1.94E-02

P01375, P49841, P06737

TNF, GSK3B, PYGL

Tibolone

hsa04932

Non-alcoholic fatty liver disease

2.74E-02

P01375, P49841, P48023

TNF, GSK3B, FASLG

Tibolone

hsa04933

AGE-RAGE signaling pathway in diabetic complications

2.11E-03

P84022, Q13485, P10415, P42338, P49767, P19174

SMAD3, SMAD4, BCL2, PIK3CB, VEGFC, PLCG1

Tibolone

hsa04940

Type I diabetes mellitus

1.87E-02

P48023, P01375

FASLG, TNF

Tibolone

hsa04960

Aldosterone-regulated sodium reabsorption

3.14E-02

P06213

INSR

Tibolone

hsa04964

Proximal tubule bicarbonate reclamation

4.53E-03

P00918, P49448

CA2, GLUD2

Tibolone

hsa04966

Collecting duct acid secretion

4.93E-02

P00918

CA2

Tibolone

hsa04972

Pancreatic secretion

3.65E-02

P63092, P61586

GNAS, RHOA

Tibolone

hsa04975

Fat digestion and absorption

9.50E-04

O14494

PLPP1

Tibolone

hsa04976

Bile secretion

2.44E-02

P22694, P08183

PRKACB, ABCB1

Tibolone

hsa05032

Morphine addiction

2.47E-03

P62873, P48169, P63092

GNB1, GABRA4, GNAS

Tibolone

hsa05034

Alcoholism

2.05E-05

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

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

Tibolone

hsa05120

Epithelial cell signaling in Helicobacter pylori infection

3.76E-02

Q16539, P09341, P25024, P25025

MAPK14, CXCL1, CXCR1, CXCR2

Tibolone

hsa05130

Pathogenic Escherichia coli infection

2.02E-04

Q14247, P56750, O00501, Q92974, P63261, P25116, Q06124, O95487

CTTN, CLDN17, CLDN5, ARHGEF2, ACTG1, F2R, PTPN11, SEC24B

Tibolone

hsa05132

Salmonella infection

5.76E-04

P25963, Q13546, Q13489, P10415, Q9BQS8, O60282, P68371

NFKBIA, RIPK1, BIRC3, BCL2, FYCO1, KIF5C, TUBB2C

Tibolone

hsa05133

Pertussis

1.86E-03

P09871, P0C0L4, Q02556

C1S, C4A, IRF8

Tibolone

hsa05135

Yersinia infection

1.52E-02

P13612, P06239, Q16539, P49841, P01730, P01732

ITGA4, LCK, MAPK14, GSK3B, CD4, CD8A

Tibolone

hsa05140

Leishmaniasis

4.50E-03

P14598, O60603, P25963, P29350, Q15080

NCF1, TLR2, NFKBIA, PTPN6, NCF4

Tibolone

hsa05143

African trypanosomiasis

7.50E-04

P01375, P69905, P68871, P48023

TNF, HBA2, HBB, FASLG

Tibolone

hsa05144

Malaria

3.09E-02

P69905, P68871

HBA2, HBB

Tibolone

hsa05145

Toxoplasmosis

2.78E-02

P25963, P10415, Q13489

NFKBIA, BCL2, BIRC3

Tibolone

hsa05146

Amoebiasis

2.10E-02

P09341, P14778, P27930, P05089, P12814, P08311

CXCL1, IL1R1, IL1R2, ARG1, ACTN1, CTSG

Tibolone

hsa05160

Hepatitis C

1.27E-02

P60033, P49841, P01375, P48023

CD81, GSK3B, TNF, FASLG

Tibolone

hsa05161

Hepatitis B

8.49E-03

P25963, Q13485, P10415, P84022

NFKBIA, SMAD4, BCL2, SMAD3

Tibolone

hsa05163

Human cytomegalovirus infection

2.09E-02

P62873, P61586, P63092, P61769

GNB1, RHOA, GNAS, B2M

Tibolone

hsa05167

Kaposi sarcoma-associated herpesvirus infection

1.94E-02

P62879, P16298, Q02750, P0CG47

GNB2, PPP3CB, MAP2K1, UBB

Tibolone

hsa05168

Herpes simplex virus 1 infection

1.15E-02

P42224, Q07955, Q01130, Q13243, P42338, Q13398, Q03923, Q9UDV6

STAT1, SFRS1, SFRS2, SFRS5, PIK3CB, ZNF211, ZNF85, ZNF212

Tibolone

hsa05170

Human immunodeficiency virus 1 infection

6.02E-03

Q02750, P62879, P16298, Q05397, P20333

MAP2K1, GNB2, PPP3CB, PTK2, TNFRSF1B

Tibolone

hsa05200

Pathways in cancer

1.31E-03

Q13751, P42338, P08238, P42224, P19174, P43246, P84022, Q13485, Q13547, P14923, P30281, P49767, P43657, P63218, P50151, Q14344, Q7LDG7, O75293, P0DP23, P14784, P40189

LAMB3, PIK3CB, HSP90AB1, STAT1, PLCG1, MSH2, SMAD3, SMAD4, HDAC1, JUP, CCND3, VEGFC, P2RY5, GNG5, GNG10, GNA13, RASGRP2, GADD45B, CALM1, IL2RB, IL6ST

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
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13751	LAMB3	Laminin subunit beta-3	0.844
P29375	JARID1A	Lysine-specific demethylase 5A	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	-0.79
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P42338	PIK3CB	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform	0.777
P29375	JARID1A	Lysine-specific demethylase 5A	P08238	HSP90AB1	Heat shock protein HSP 90-beta	0.711
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P08238	HSP90AB1	Heat shock protein HSP 90-beta	-0.823
P29375	JARID1A	Lysine-specific demethylase 5A	P42224	STAT1	Signal transducer and activator of transcription 1-alpha/beta	0.764
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P19174	PLCG1	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1	-0.766
P29375	JARID1A	Lysine-specific demethylase 5A	P43246	MSH2	DNA mismatch repair protein Msh2	0.87
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P43246	MSH2	DNA mismatch repair protein Msh2	-0.811
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P84022	SMAD3	Mothers against decapentaplegic homolog 3	0.725
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13485	SMAD4	Mothers against decapentaplegic homolog 4	-0.746
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q13547	HDAC1	Histone deacetylase 1	-0.754
P29375	JARID1A	Lysine-specific demethylase 5A	P14923	JUP	Junction plakoglobin	-0.735
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P30281	CCND3	G1/S-specific cyclin-D3	0.743
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P49767	VEGFC	Vascular endothelial growth factor C	0.743
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P43657	P2RY5	Lysophosphatidic acid receptor 6	-0.735
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P63218	GNG5	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5	0.941
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P50151	GNG10	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10	0.948
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q14344	GNA13	Guanine nucleotide-binding protein subunit alpha-13	0.87
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	Q7LDG7	RASGRP2	RAS guanyl-releasing protein 2	0.704
P29375	JARID1A	Lysine-specific demethylase 5A	O75293	GADD45B	Growth arrest and DNA damage-inducible protein GADD45 beta	-0.748
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	O75293	GADD45B	Growth arrest and DNA damage-inducible protein GADD45 beta	0.731
P29375	JARID1A	Lysine-specific demethylase 5A	P0DP23	CALM1	Calmodulin-1	0.755
P29375	JARID1A	Lysine-specific demethylase 5A	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.768
P09917	ALOX5	Polyunsaturated fatty acid 5-lipoxygenase	P14784	IL2RB	Interleukin-2 receptor subunit beta	-0.835
P29375	JARID1A	Lysine-specific demethylase 5A	P40189	IL6ST	Interleukin-6 receptor subunit beta	0.83

Tibolone

hsa05202

Transcriptional misregulation in cancer

8.55E-04

P27930, P11215, P08069, Q13547, P12980

IL1R2, ITGAM, IGF1R, HDAC1, LYL1

Tibolone

hsa05203

Viral carcinogenesis

1.22E-03

Q13547, Q15283, P58876, P62807, Q16778, O60814

HDAC1, RASA2, H2BC5, HIST1H2BC, HIST2H2BE, H2BC12

Tibolone

hsa05204

Chemical carcinogenesis

1.48E-02

P78417, P11712

GSTO1, CYP2C9

Tibolone

hsa05205

Proteoglycans in cancer

3.48E-02

P08069

IGF1R

Tibolone

hsa05210

Colorectal cancer

1.78E-02

P84022, Q13485, P10415

SMAD3, SMAD4, BCL2

Tibolone

hsa05211

Renal cell carcinoma

1.06E-02

Q06124, Q99814

PTPN11, EPAS1

Tibolone

hsa05212

Pancreatic cancer

2.34E-04

P42338, P42224, P84022, Q13485, O75293

PIK3CB, STAT1, SMAD3, SMAD4, GADD45B

Tibolone

hsa05213

Endometrial cancer

3.79E-02

O15169, Q02750

AXIN1, MAP2K1

Tibolone

hsa05214

Glioma

1.88E-03

P08069, P0DP23, P42338, O75293

IGF1R, CALM1, PIK3CB, GADD45B

Tibolone

hsa05215

Prostate cancer

1.33E-02

P08069

IGF1R

Tibolone

hsa05216

Thyroid cancer

3.80E-02

P01106, O75293

MYC, GADD45B

Tibolone

hsa05218

Melanoma

6.63E-03

P08069

IGF1R

Tibolone

hsa05220

Chronic myeloid leukemia

1.44E-03

Q13547, Q13485, P25963, P84022, P42338, O75293

HDAC1, SMAD4, NFKBIA, SMAD3, PIK3CB, GADD45B

Tibolone

hsa05222

Small cell lung cancer

1.50E-02

Q13489, P10415, P25963

BIRC3, BCL2, NFKBIA

Tibolone

hsa05223

Non-small cell lung cancer

1.39E-02

P10826, Q9HC35, O75293

RARB, EML4, GADD45B

Tibolone

hsa05224

Breast cancer

1.49E-02

P08069

IGF1R

Tibolone

hsa05225

Hepatocellular carcinoma

1.33E-02

P08069

IGF1R

Tibolone

hsa05226

Gastric cancer

4.33E-03

Q02750, O15169, P84022, Q13485, P10415

MAP2K1, AXIN1, SMAD3, SMAD4, BCL2

Tibolone

hsa05230

Central carbon metabolism in cancer

1.12E-02

P11413

G6PD

Tibolone

hsa05235

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

1.92E-04

P07766, P20963, P09693, P06239, Q04759, Q16539, Q9HC35, P01730

CD3E, CD247, CD3G, LCK, PRKCQ, MAPK14, EML4, CD4

Tibolone

hsa05322

Systemic lupus erythematosus

4.80E-06

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

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

Tibolone

hsa05330

Allograft rejection

2.72E-02

P48023, P01375

FASLG, TNF

Tibolone

hsa05332

Graft-versus-host disease

3.70E-02

P48023, P01375

FASLG, TNF

Tibolone

hsa05340

Primary immunodeficiency

2.90E-04

P01730, P01732, P11912, P07766, P06239

CD4, CD8A, CD79A, CD3E, LCK

Tibolone

hsa05412

Arrhythmogenic right ventricular cardiomyopathy

4.93E-02

P54284

CACNB3

Tibolone

hsa05415

Diabetic cardiomyopathy

3.59E-02

P11413

G6PD

Tibolone

hsa05418

Fluid shear stress and atherosclerosis

3.73E-02

P42338, P14598, P0DP23, P08238

PIK3CB, NCF1, CALM1, HSP90AB1

Community members of Tibolone (S_DC: 7.38)

UniProtAC

Gene Name

Protein Name

Reported/
Predicted

S_PV

CYP19A1

Aromatase

Predicted

0.8156

0.1588

2.5666

P14416

DRD2

D(2) dopamine receptor

Predicted

0.0604

0.4779

2.5081

P11413

G6PD

GlucoseNone6Nonephosphate 1Nonedehydrogenase

Predicted

0.4435

0.6369

0.2929

1.7884

Q06124

PTPN11

TyrosineNoneprotein phosphatase nonNonereceptor type 11

Predicted

0.1513

0.4566

0.613

1.6017

P06213

INSR

Insulin receptor

Predicted

0.2794

0.7813

0.7209

2.4232

P08069

IGF1R

InsulinNonelike growth factor 1 receptor

Predicted

0.2082

0.9561

0.9883

3.0047

P49336

CDK8

CyclinNonedependent kinase 8

Predicted

0.1356

0.647

1.3618

P48169

GABRA4

GammaNoneaminobutyric acid receptor subunit alphaNone4

Predicted

0.3253

0.565

0.1579

1.4506

P08235

NR3C2

Mineralocorticoid receptor

Predicted

0.1855

0.0137

2.1064

P29375

JARID1A

LysineNonespecific demethylase 5A

Predicted

0.3605

0.7052

1.5906

P35610

SOAT1

Sterol ONoneacyltransferase 1

Predicted

0.3855

0.2936

0.0165

0.7964

P11712

CYP2C9

Cytochrome P450 2C9

Predicted

0.0106

0.1524

2.1577

P08183

ABCB1

ATPNonedependent translocase ABCB1

Predicted

0.0788

0.2052

2.2446

O15245

SLC22A1

Solute carrier family 22 member 1

Predicted

0.0149

0.0219

2.0294

P09874

PARP1

Poly [ADPNoneribose] polymerase 1

Predicted

0.5536

0.4482

2.725

O43451

MGAM

MaltaseNoneglucoamylase

Predicted

0.1954

0.1678

0.191

0.6242

P18054

ALOX12

Polyunsaturated fatty acid lipoxygenase ALOX12

Predicted

0.0075

0.3703

0.2416

0.986

P09917

ALOX5

Polyunsaturated fatty acid 5Nonelipoxygenase

Predicted

0.3822

0.2701

2.4612

O75469

NR1I2

Nuclear receptor subfamily 1 group I member 2

Predicted

0.0315

0.9493

1.9143

P00918

CA2

Carbonic anhydrase 2

Predicted

0.1125

0.2215

2.2778

Q9HB89

NMUR1

NeuromedinNoneU receptor 1

Predicted

0.0024

0.303

0.6072

P52732

KIF11

KinesinNonelike protein KIF11

Predicted

0.0082

0.8281

1.6602

PharmaCoNets of Tibolone (SPCN: 145.43 )

Tibolone regulated-network (SDN: 19.71)

Community members of Tibolone (SDC: 7.38)

PharmaCoNets of Tibolone (S_PCN: 145.43 )

Tibolone regulated-network (S_DN: 19.71)

Community members of Tibolone (S_DC: 7.38)