PharmaCoNets

PharmaCoNets of Ripretinib (S_PCN: 102.60 )

Ripretinib regulated-network (S_DN: 16.66)

Drug Name

Pathway ID

Pathway name

P-value

No. of gene members

UniProt AC

Gene name

Detail of Coexpression

Ripretinib

hsa00071

Fatty acid degradation

3.50E-02

O75521, P00325, P11766, P33121

ECI2, ADH1B, ADH5, ACSL1

Ripretinib

hsa00220

Arginine biosynthesis

3.83E-02

P05089, P49448

ARG1, GLUD2

Ripretinib

hsa00500

Starch and sucrose metabolism

2.21E-03

O43451, P46976, P35573, P06737

MGAM, GYG1, AGL, PYGL

Ripretinib

hsa00730

Thiamine metabolism

4.07E-02

P05186, P24666

ALPL, ACP1

Ripretinib

hsa00830

Retinol metabolism

2.27E-03

P00325, P11766, P00352, Q9BPW9, O75911

ADH1B, ADH5, ALDH1A1, DHRS9, DHRS3

Ripretinib

hsa00970

Aminoacyl-tRNA biosynthesis

2.12E-02

P14868

DARS

Ripretinib

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

Ripretinib

hsa01521

EGFR tyrosine kinase inhibitor resistance

1.82E-02

P04049

RAF1

Ripretinib

hsa01522

Endocrine resistance

2.16E-02

P04049

RAF1

Ripretinib

hsa02010

ABC transporters

4.48E-02

Q8IZY2

ABCA7

Ripretinib

hsa03013

RNA transport

8.18E-05

P38919, Q15287, Q9UBU9, P37198, P35658, P63279, P55884, O15371, P20042

EIF4A3, RNPS1, NXF1, NUP62, NUP214, UBE2I, EIF3B, EIF3D, EIF2S2

Ripretinib

hsa03040

Spliceosome

3.98E-02

Q15427, P38159, P61978, P11142

SF3B4, RBMX, HNRPK, HSPA8

Ripretinib

hsa03060

Protein export

1.43E-02

P37108, Q15005

SRP14, SPCS2

Ripretinib

hsa03450

Non-homologous end-joining

4.21E-02

P13010

XRCC5

Ripretinib

hsa04010

MAPK signaling pathway

4.15E-02

P04049

RAF1

Ripretinib

hsa04012

ErbB signaling pathway

8.14E-03

P21860, Q13557, O14944, P04049

ERBB3, CAMK2D, EREG, RAF1

Ripretinib

hsa04014

Ras signaling pathway

3.65E-02

P04049

RAF1

Ripretinib

hsa04015

Rap1 signaling pathway

2.99E-02

P04049

RAF1

Ripretinib

hsa04020

Calcium signaling pathway

6.50E-04

Q96DU7, P45880, Q13557, P21860, P51828, P23634

ITPKC, VDAC2, CAMK2D, ERBB3, ADCY7, ATP2B4

Ripretinib

hsa04022

cGMP-PKG signaling pathway

1.40E-02

P04049, Q99941, P23634, P51828, P45880

RAF1, CREBL1, ATP2B4, ADCY7, VDAC2

Ripretinib

hsa04024

cAMP signaling pathway

2.49E-02

P04049

RAF1

Ripretinib

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

Ripretinib

hsa04061

Viral protein interaction with cytokine and cytokine receptor

1.32E-02

P09341, P25024, P47992, Q9UBD3, Q13651, P14784

CXCL1, CXCR1, XCL1, XCL2, IL10RA, IL2RB

Ripretinib

hsa04062

Chemokine signaling pathway

2.83E-03

P25024, P09341, P47992, Q9UBD3, P07948, P63218, P50151, P43250, Q08881, P04049

CXCR1, CXCL1, XCL1, XCL2, LYN, GNG5, GNG10, GRK6, ITK, RAF1

Ripretinib

hsa04064

NF-kappa B signaling pathway

3.28E-05

O00463, P14778, P01584, P01375, Q04759, Q13077, Q16548, P07948, P06239, Q8WV28, P24522, P09341, Q06643, Q9NQC7

TRAF5, IL1R1, IL1B, TNF, PRKCQ, TRAF1, BCL2A1, LYN, LCK, BLNK, GADD45A, CXCL1, LTB, CYLD

Genes in community(ComG)	Gene name of ComG	Protein name of ComG	Co-expressed genes in pathway (PathG)	Gene name of PathG	Protein name of PathG	Coexpression
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O00463	TRAF5	TNF receptor-associated factor 5	-0.932
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
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P14778	IL1R1	Interleukin-1 receptor type 1	0.766
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
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01584	IL1B	Interleukin-1 beta	0.807
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01375	TNF	Tumor necrosis factor	0.78
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q04759	PRKCQ	Protein kinase C theta type	-0.767
P06239	LCK	Tyrosine-protein kinase Lck	Q04759	PRKCQ	Protein kinase C theta type	0.779
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q13077	TRAF1	TNF receptor-associated factor 1	-0.796
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q13077	TRAF1	TNF receptor-associated factor 1	-0.73
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q16548	BCL2A1	Bcl-2-related protein A1	0.958
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q16548	BCL2A1	Bcl-2-related protein A1	0.875
P06239	LCK	Tyrosine-protein kinase Lck	P07948	LYN	Tyrosine-protein kinase Lyn	-0.701
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P06239	LCK	Tyrosine-protein kinase Lck	-0.726
P06239	LCK	Tyrosine-protein kinase Lck	P06239	LCK	Tyrosine-protein kinase Lck	1
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q8WV28	BLNK	B-cell linker protein	-0.704
Q16539	MAPK14	Mitogen-activated protein kinase 14	Q8WV28	BLNK	B-cell linker protein	-0.816
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P24522	GADD45A	Growth arrest and DNA damage-inducible protein GADD45 alpha	0.819
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
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P09341	CXCL1	Growth-regulated alpha protein	0.788
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
P06239	LCK	Tyrosine-protein kinase Lck	Q06643	LTB	Lymphotoxin-beta	0.846
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q9NQC7	CYLD	Ubiquitin carboxyl-terminal hydrolase CYLD	0.799

Ripretinib

hsa04068

FoxO signaling pathway

1.99E-02

P04049

RAF1

Ripretinib

hsa04071

Sphingolipid signaling pathway

2.16E-02

P04049

RAF1

Ripretinib

hsa04072

Phospholipase D signaling pathway

2.82E-02

P04049

RAF1

Ripretinib

hsa04140

Autophagy - animal

2.82E-02

P04049

RAF1

Ripretinib

hsa04141

Protein processing in endoplasmic reticulum

3.64E-02

Q99941, O75460, P11142, Q9H3Z4, P07900

CREBL1, ERN1, HSPA8, DNAJC5, HSP90AA1

Ripretinib

hsa04150

mTOR signaling pathway

2.32E-02

P04049

RAF1

Ripretinib

hsa04210

Apoptosis

2.16E-02

P04049

RAF1

Ripretinib

hsa04218

Cellular senescence

2.49E-02

P04049

RAF1

Ripretinib

hsa04261

Adrenergic signaling in cardiomyocytes

3.98E-02

P51828, Q99941, Q13557, P23634

ADCY7, CREBL1, CAMK2D, ATP2B4

Ripretinib

hsa04270

Vascular smooth muscle contraction

2.32E-02

P04049

RAF1

Ripretinib

hsa04330

Notch signaling pathway

2.46E-03

Q92542, P49768, P46531

NCSTN, PSEN1, NOTCH1

Ripretinib

hsa04360

Axon guidance

2.49E-02

P04049

RAF1

Ripretinib

hsa04370

VEGF signaling pathway

8.29E-03

P04049

RAF1

Ripretinib

hsa04371

Apelin signaling pathway

2.65E-02

P04049

RAF1

Ripretinib

hsa04380

Osteoclast differentiation

2.05E-03

Q9NQC7, Q9UQC2, Q16539, P23458, P06239, P01584, P14778, O75015, Q8WV28, P01375, Q15080, P78324

CYLD, GAB2, MAPK14, JAK1, LCK, IL1B, IL1R1, FCGR3B, BLNK, TNF, NCF4, SIRPA

Ripretinib

hsa04510

Focal adhesion

3.48E-02

P04049

RAF1

Ripretinib

hsa04540

Gap junction

1.33E-02

P04049

RAF1

Ripretinib

hsa04550

Signaling pathways regulating pluripotency of stem cells

1.99E-02

P04049

RAF1

Ripretinib

hsa04610

Complement and coagulation cascades

1.91E-03

P0C0L4

C4A

Ripretinib

hsa04612

Antigen processing and presentation

1.75E-02

P13765, P01730, P26715, P26717, Q13241, P01732

HLA-DOB, CD4, KLRC1, KLRC2, KLRD1, CD8A

Ripretinib

hsa04613

Neutrophil extracellular trap formation

3.72E-03

P04049, O60603, P05164, P08246, Q9UM07, Q13547, Q92769, P0C0S5, Q15080, P08311, O75015, P21730, P21462, O43315, Q16539

RAF1, TLR2, MPO, ELA2, PADI4, HDAC1, HDAC2, H2AFZ, NCF4, CTSG, FCGR3B, C5AR1, FPR1, AQP9, MAPK14

Ripretinib

hsa04614

Renin-angiotensin system

2.74E-02

P15144, P08311, O75787

ANPEP, CTSG, ATP6AP2

Ripretinib

hsa04625

C-type lectin receptor signaling pathway

1.88E-03

Q9ULY5, P04049, P01584, Q9NQC7, P20749, Q14643, P01375, Q13191, P0DP24, Q16539

CLEC4E, RAF1, IL1B, CYLD, BCL3, ITPR1, TNF, CBLB, CALM2, MAPK14

Ripretinib

hsa04630

JAK-STAT signaling pathway

1.49E-02

P04049

RAF1

Ripretinib

hsa04640

Hematopoietic cell lineage

1.16E-04

P13612, P14778, P27930, P15144, P11836, P25063, P07766, P09693, P01732, P01730, P09564, P13765, P01375, P01584

ITGA4, IL1R1, IL1R2, ANPEP, MS4A1, CD24, CD3E, CD3G, CD8A, CD4, CD7, HLA-DOB, TNF, IL1B

Ripretinib

hsa04650

Natural killer cell mediated cytotoxicity

8.58E-05

P01375, P78314, P06239, O60880, P20963, P04049, Q13241, P26718, O14931, O75015, P26717, P26715

TNF, SH3BP2, LCK, SH2D1A, CD247, RAF1, 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
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01375	TNF	Tumor necrosis factor	0.78
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P78314	SH3BP2	SH3 domain-binding protein 2	0.761
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P06239	LCK	Tyrosine-protein kinase Lck	-0.726
P06239	LCK	Tyrosine-protein kinase Lck	P06239	LCK	Tyrosine-protein kinase Lck	1
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O60880	SH2D1A	SH2 domain-containing protein 1A	-0.823
P06239	LCK	Tyrosine-protein kinase Lck	O60880	SH2D1A	SH2 domain-containing protein 1A	0.906
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.786
P06239	LCK	Tyrosine-protein kinase Lck	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.927
P04049	RAF1	RAF proto-oncogene serine/threonine-protein kinase	P04049	RAF1	RAF proto-oncogene serine/threonine-protein kinase	1
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q13241	KLRD1	Natural killer cells antigen CD94	-0.82
P06239	LCK	Tyrosine-protein kinase Lck	Q13241	KLRD1	Natural killer cells antigen CD94	0.758
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P26718	KLRK1	NKG2-D type II integral membrane protein	-0.91
P06239	LCK	Tyrosine-protein kinase Lck	P26718	KLRK1	NKG2-D type II integral membrane protein	0.886
P06239	LCK	Tyrosine-protein kinase Lck	O14931	NCR3	Natural cytotoxicity triggering receptor 3	0.732
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O75015	FCGR3B	Low affinity immunoglobulin gamma Fc region receptor III-B	0.92
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P26717	KLRC2	NKG2-C type II integral membrane protein	-0.846
P06239	LCK	Tyrosine-protein kinase Lck	P26717	KLRC2	NKG2-C type II integral membrane protein	0.756
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	-0.846
P06239	LCK	Tyrosine-protein kinase Lck	P26715	KLRC1	NKG2-A/NKG2-B type II integral membrane protein	0.756

Ripretinib

hsa04657

IL-17 signaling pathway

2.25E-03

O00463, Q16539, P49841, P09341, P14780, P80188, P01375, P01584

TRAF5, MAPK14, GSK3B, CXCL1, MMP9, LCN2, TNF, IL1B

Ripretinib

hsa04658

Th1 and Th2 cell differentiation

3.56E-07

Q04759, P07766, P20963, P09693, Q16539, P01730, P06239, Q14765, P23771, Q9UL17, P14784, P13765, P23458, Q13761

PRKCQ, CD3E, CD247, CD3G, MAPK14, CD4, LCK, STAT4, GATA3, TBX21, IL2RB, HLA-DOB, JAK1, 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
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q04759	PRKCQ	Protein kinase C theta type	-0.767
P06239	LCK	Tyrosine-protein kinase Lck	Q04759	PRKCQ	Protein kinase C theta type	0.779
P06239	LCK	Tyrosine-protein kinase Lck	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.928
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.786
P06239	LCK	Tyrosine-protein kinase Lck	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.927
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.835
P06239	LCK	Tyrosine-protein kinase Lck	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	0.752
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.883
P06239	LCK	Tyrosine-protein kinase Lck	P01730	CD4	T-cell surface glycoprotein CD4	0.746
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P06239	LCK	Tyrosine-protein kinase Lck	-0.726
P06239	LCK	Tyrosine-protein kinase Lck	P06239	LCK	Tyrosine-protein kinase Lck	1
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q14765	STAT4	Signal transducer and activator of transcription 4	-0.777
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.763
P06239	LCK	Tyrosine-protein kinase Lck	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	0.77
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q9UL17	TBX21	T-box transcription factor TBX21	-0.872
P06239	LCK	Tyrosine-protein kinase Lck	Q9UL17	TBX21	T-box transcription factor TBX21	0.866
P06239	LCK	Tyrosine-protein kinase Lck	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.727
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.785
P06239	LCK	Tyrosine-protein kinase Lck	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	0.777
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23458	JAK1	Tyrosine-protein kinase JAK1	0.757
P06239	LCK	Tyrosine-protein kinase Lck	Q13761	RUNX3	Runt-related transcription factor 3	0.85

Ripretinib

hsa04659

Th17 cell differentiation

2.50E-06

Q04759, Q16539, P01730, P06239, P14784, P13765, P14778, Q9UL17, P23771, P01584, P07766, P09693, P20963, P23458

PRKCQ, MAPK14, CD4, LCK, IL2RB, HLA-DOB, IL1R1, TBX21, GATA3, IL1B, CD3E, CD3G, CD247, JAK1

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
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q04759	PRKCQ	Protein kinase C theta type	-0.767
P06239	LCK	Tyrosine-protein kinase Lck	Q04759	PRKCQ	Protein kinase C theta type	0.779
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.883
P06239	LCK	Tyrosine-protein kinase Lck	P01730	CD4	T-cell surface glycoprotein CD4	0.746
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P06239	LCK	Tyrosine-protein kinase Lck	-0.726
P06239	LCK	Tyrosine-protein kinase Lck	P06239	LCK	Tyrosine-protein kinase Lck	1
P06239	LCK	Tyrosine-protein kinase Lck	P14784	IL2RB	Interleukin-2 receptor subunit beta	0.727
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	-0.785
P06239	LCK	Tyrosine-protein kinase Lck	P13765	HLA-DOB	HLA class II histocompatibility antigen, DO beta chain	0.777
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P14778	IL1R1	Interleukin-1 receptor type 1	0.766
P06239	LCK	Tyrosine-protein kinase Lck	P14778	IL1R1	Interleukin-1 receptor type 1	-0.782
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q9UL17	TBX21	T-box transcription factor TBX21	-0.872
P06239	LCK	Tyrosine-protein kinase Lck	Q9UL17	TBX21	T-box transcription factor TBX21	0.866
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	-0.763
P06239	LCK	Tyrosine-protein kinase Lck	P23771	GATA3	Trans-acting T-cell-specific transcription factor GATA-3	0.77
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01584	IL1B	Interleukin-1 beta	0.807
P06239	LCK	Tyrosine-protein kinase Lck	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.928
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.835
P06239	LCK	Tyrosine-protein kinase Lck	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	0.752
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.786
P06239	LCK	Tyrosine-protein kinase Lck	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.927
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23458	JAK1	Tyrosine-protein kinase JAK1	0.757

Ripretinib

hsa04660

T cell receptor signaling pathway

6.52E-06

P01375, Q04759, O95267, Q08881, P07766, P20963, P09693, P01730, P01732, Q13191, P06239, P04049, Q16539, P49841

TNF, PRKCQ, RASGRP1, ITK, CD3E, CD247, CD3G, CD4, CD8A, CBLB, LCK, RAF1, 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
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01375	TNF	Tumor necrosis factor	0.78
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q04759	PRKCQ	Protein kinase C theta type	-0.767
P06239	LCK	Tyrosine-protein kinase Lck	Q04759	PRKCQ	Protein kinase C theta type	0.779
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.852
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	-0.866
P06239	LCK	Tyrosine-protein kinase Lck	Q08881	ITK	Tyrosine-protein kinase ITK/TSK	0.774
P06239	LCK	Tyrosine-protein kinase Lck	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.928
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.786
P06239	LCK	Tyrosine-protein kinase Lck	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.927
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.835
P06239	LCK	Tyrosine-protein kinase Lck	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	0.752
P06239	LCK	Tyrosine-protein kinase Lck	P01730	CD4	T-cell surface glycoprotein CD4	0.746
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	-0.781
P06239	LCK	Tyrosine-protein kinase Lck	P01732	CD8A	T-cell surface glycoprotein CD8 alpha chain	0.841
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	-0.803
P06239	LCK	Tyrosine-protein kinase Lck	Q13191	CBLB	E3 ubiquitin-protein ligase CBL-B	0.714
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P06239	LCK	Tyrosine-protein kinase Lck	-0.726
P06239	LCK	Tyrosine-protein kinase Lck	P06239	LCK	Tyrosine-protein kinase Lck	1
P04049	RAF1	RAF proto-oncogene serine/threonine-protein kinase	P04049	RAF1	RAF proto-oncogene serine/threonine-protein kinase	1
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.883
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P49841	GSK3B	Glycogen synthase kinase-3 beta	0.812

Ripretinib

hsa04662

B cell receptor signaling pathway

9.95E-03

P04049

RAF1

Ripretinib

hsa04664

Fc epsilon RI signaling pathway

1.16E-02

P04049

RAF1

Ripretinib

hsa04666

Fc gamma R-mediated phagocytosis

2.32E-02

P04049

RAF1

Ripretinib

hsa04668

TNF signaling pathway

4.74E-02

Q99941, P01584, O95429

CREBL1, IL1B, BAG4

Ripretinib

hsa04720

Long-term potentiation

1.66E-02

P04049

RAF1

Ripretinib

hsa04722

Neurotrophin signaling pathway

2.32E-02

P04049

RAF1

Ripretinib

hsa04726

Serotonergic synapse

1.33E-02

P04049

RAF1

Ripretinib

hsa04730

Long-term depression

1.16E-02

P04049

RAF1

Ripretinib

hsa04750

Inflammatory mediator regulation of TRP channels

1.51E-03

P14778, P01584, P51828, P22694, Q13557, Q16539, Q14643, Q04759, P0DP24

IL1R1, IL1B, ADCY7, PRKACB, CAMK2D, MAPK14, ITPR1, PRKCQ, CALM2

Ripretinib

hsa04810

Regulation of actin cytoskeleton

3.81E-02

P04049

RAF1

Ripretinib

hsa04910

Insulin signaling pathway

1.49E-02

P04049

RAF1

Ripretinib

hsa04911

Insulin secretion

1.48E-02

P51828, Q99941, Q13557

ADCY7, CREBL1, CAMK2D

Ripretinib

hsa04912

GnRH signaling pathway

2.74E-02

P51828, Q16539, Q9Y6R4, Q14643, P0DP24, P22694, P04049

ADCY7, MAPK14, MAP3K4, ITPR1, CALM2, PRKACB, RAF1

Ripretinib

hsa04914

Progesterone-mediated oocyte maturation

2.16E-02

P04049

RAF1

Ripretinib

hsa04915

Estrogen signaling pathway

1.26E-02

P04049, Q99941, P51828, P07900, P11142

RAF1, CREBL1, ADCY7, HSP90AA1, HSPA8

Ripretinib

hsa04916

Melanogenesis

1.33E-02

P04049

RAF1

Ripretinib

hsa04917

Prolactin signaling pathway

6.63E-03

P04049

RAF1

Ripretinib

hsa04919

Thyroid hormone signaling pathway

1.82E-02

P04049

RAF1

Ripretinib

hsa04921

Oxytocin signaling pathway

2.32E-02

P04049

RAF1

Ripretinib

hsa04925

Aldosterone synthesis and secretion

5.19E-03

Q99941, P51828, Q13557, P23634

CREBL1, ADCY7, CAMK2D, ATP2B4

Ripretinib

hsa04926

Relaxin signaling pathway

2.32E-02

P04049

RAF1

Ripretinib

hsa04928

Parathyroid hormone synthesis, secretion and action

1.99E-02

P04049

RAF1

Ripretinib

hsa04929

GnRH secretion

4.98E-03

P04049

RAF1

Ripretinib

hsa04934

Cushing syndrome

3.48E-03

Q99941, P51828, O15169, Q13557

CREBL1, ADCY7, AXIN1, CAMK2D

Ripretinib

hsa04935

Growth hormone synthesis, secretion and action

2.16E-02

P04049

RAF1

Ripretinib

hsa04964

Proximal tubule bicarbonate reclamation

4.48E-02

P00918

CA2

Ripretinib

hsa04966

Collecting duct acid secretion

4.48E-02

P00918

CA2

Ripretinib

hsa04971

Gastric acid secretion

1.48E-02

P51828, P15311, Q13557

ADCY7, VIL2, CAMK2D

Ripretinib

hsa05010

Alzheimer disease

2.07E-02

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

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

Ripretinib

hsa05020

Prion disease

1.81E-02

P01584, P46531, P11142, P05496, P12074, P45880, Q99941

IL1B, NOTCH1, HSPA8, ATP5G1, COX6A1, VDAC2, CREBL1

Ripretinib

hsa05034

Alcoholism

2.49E-02

P04049

RAF1

Ripretinib

hsa05120

Epithelial cell signaling in Helicobacter pylori infection

2.45E-02

Q16539, P09341, P25024, P25025

MAPK14, CXCL1, CXCR1, CXCR2

Ripretinib

hsa05132

Salmonella infection

4.98E-02

P04049

RAF1

Ripretinib

hsa05133

Pertussis

3.51E-02

P0C0L4

C4A

Ripretinib

hsa05140

Leishmaniasis

1.93E-03

P13612, O75015, P23458, P13765, O60603, P01375, P01584, P49006, Q16539, Q15080

ITGA4, FCGR3B, JAK1, HLA-DOB, TLR2, TNF, IL1B, MARCKSL1, MAPK14, NCF4

Ripretinib

hsa05144

Malaria

2.43E-02

P60033, O60603, P01375, P35443, P01584, P26718

CD81, TLR2, TNF, THBS4, IL1B, KLRK1

Ripretinib

hsa05146

Amoebiasis

2.57E-04

P01584, P09341, P14778, P27930, P01375, O60603, P05089, P22694, P12814, P08311

IL1B, CXCL1, IL1R1, IL1R2, TNF, TLR2, ARG1, PRKACB, ACTN1, CTSG

Ripretinib

hsa05150

Staphylococcus aureus infection

1.31E-02

P0C0L4, P13646

C4A, KRT13

Ripretinib

hsa05152

Tuberculosis

3.98E-02

P04049

RAF1

Ripretinib

hsa05160

Hepatitis C

1.99E-02

P04049

RAF1

Ripretinib

hsa05161

Hepatitis B

1.99E-02

P04049

RAF1

Ripretinib

hsa05163

Human cytomegalovirus infection

4.00E-02

P04049, Q14643, P49841, P14778, P25025, Q16539, P04637, O00463

RAF1, ITPR1, GSK3B, IL1R1, CXCR2, MAPK14, TP53, TRAF5

Ripretinib

hsa05164

Influenza A

3.65E-02

P04049

RAF1

Ripretinib

hsa05167

Kaposi sarcoma-associated herpesvirus infection

3.15E-02

P04049

RAF1

Ripretinib

hsa05169

Epstein-Barr virus infection

4.84E-03

P13765, P01106, Q13547, O00463, P07948, Q13761, P24522, P07766, P09693, P20963

HLA-DOB, MYC, HDAC1, TRAF5, LYN, RUNX3, GADD45A, CD3E, CD3G, CD247

Ripretinib

hsa05170

Human immunodeficiency virus 1 infection

3.48E-02

P04049

RAF1

Ripretinib

hsa05202

Transcriptional misregulation in cancer

6.59E-03

P17844, P14780, P27930, Q16548, Q13077, P35226, P05164, P12838, P08246, Q9C0K0, P41182, Q13547, Q92769, P12980, P24522

DDX5, MMP9, IL1R2, BCL2A1, TRAF1, BMI1, MPO, DEFA4, ELA2, BCL11B, BCL6, HDAC1, HDAC2, LYL1, GADD45A

Ripretinib

hsa05205

Proteoglycans in cancer

3.48E-02

P04049

RAF1

Ripretinib

hsa05206

MicroRNAs in cancer

6.19E-04

P15311, P21860, P61978, P46531, P63279, P22105, P04049

VIL2, ERBB3, HNRPK, NOTCH1, UBE2I, TNXB, RAF1

Ripretinib

hsa05210

Colorectal cancer

1.66E-02

P04049

RAF1

Ripretinib

hsa05211

Renal cell carcinoma

1.16E-02

P04049

RAF1

Ripretinib

hsa05212

Pancreatic cancer

1.16E-02

P04049

RAF1

Ripretinib

hsa05213

Endometrial cancer

9.95E-03

P04049

RAF1

Ripretinib

hsa05214

Glioma

9.95E-03

P04049

RAF1

Ripretinib

hsa05215

Prostate cancer

1.33E-02

P04049

RAF1

Ripretinib

hsa05217

Basal cell carcinoma

3.50E-02

Q13635, P49841, Q9UJU2, P24522

PTCH1, GSK3B, LEF1, GADD45A

Ripretinib

hsa05218

Melanoma

6.63E-03

P04049

RAF1

Ripretinib

hsa05219

Bladder cancer

5.65E-03

P14780, P04637, P04049

MMP9, TP53, RAF1

Ripretinib

hsa05220

Chronic myeloid leukemia

9.95E-03

P04049

RAF1

Ripretinib

hsa05221

Acute myeloid leukemia

8.29E-03

P04049

RAF1

Ripretinib

hsa05223

Non-small cell lung cancer

6.63E-03

P04049

RAF1

Ripretinib

hsa05224

Breast cancer

1.24E-02

P04049, P49841, Q92837, P04637, P24522

RAF1, GSK3B, FRAT1, TP53, GADD45A

Ripretinib

hsa05225

Hepatocellular carcinoma

1.33E-02

P04049

RAF1

Ripretinib

hsa05226

Gastric cancer

8.29E-03

P04049

RAF1

Ripretinib

hsa05230

Central carbon metabolism in cancer

9.95E-03

P04049

RAF1

Ripretinib

hsa05231

Choline metabolism in cancer

1.33E-02

P04049

RAF1

Ripretinib

hsa05235

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

6.00E-05

O95267, P07766, P20963, P09693, P06239, P04049, P23458, O60603, Q04759, Q16539, P01730

RASGRP1, CD3E, CD247, CD3G, LCK, RAF1, JAK1, TLR2, 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
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.852
Q16539	MAPK14	Mitogen-activated protein kinase 14	O95267	RASGRP1	RAS guanyl-releasing protein 1	-0.716
P06239	LCK	Tyrosine-protein kinase Lck	P07766	CD3E	T-cell surface glycoprotein CD3 epsilon chain	0.928
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	-0.786
P06239	LCK	Tyrosine-protein kinase Lck	P20963	CD247	T-cell surface glycoprotein CD3 zeta chain	0.927
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P09693	CD3G	T-cell surface glycoprotein CD3 gamma chain	-0.835
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
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P06239	LCK	Tyrosine-protein kinase Lck	-0.726
P06239	LCK	Tyrosine-protein kinase Lck	P06239	LCK	Tyrosine-protein kinase Lck	1
P04049	RAF1	RAF proto-oncogene serine/threonine-protein kinase	P04049	RAF1	RAF proto-oncogene serine/threonine-protein kinase	1
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	P23458	JAK1	Tyrosine-protein kinase JAK1	0.757
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	O60603	TLR2	Toll-like receptor 2	0.842
Q16539	MAPK14	Mitogen-activated protein kinase 14	O60603	TLR2	Toll-like receptor 2	0.73
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q04759	PRKCQ	Protein kinase C theta type	-0.767
P06239	LCK	Tyrosine-protein kinase Lck	Q04759	PRKCQ	Protein kinase C theta type	0.779
P43490	PBEF1	Nicotinamide phosphoribosyltransferase	Q16539	MAPK14	Mitogen-activated protein kinase 14	0.883
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