Hepatocellular carcinoma

Summary

Hepatocellular carcinoma (MONDO:0007256) is a cancer (an umbrella term covering 8 Mondo subtypes) with 53 cohort genes (108 GWAS associations across 34 studies; 22 CIViC-evidence somatic drivers; 403 ClinVar predisposition records) and 2,567 clinical trials. The dominant Reactome pathway is TCF dependent signaling in response to WNT (6 cohort genes). Molecularly, FGF19 Overexpression confers sensitivity to Fisogatinib in Hepatocellular Carcinoma (CIViC Level B); 13 further subtype–drug associations are mapped below. Top therapeutic interventions include chlorotrianisene, sorafenib, and lenvatinib.

At a glance

• Classification: Cancer
• Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
• Umbrella term: 8 Mondo subtypes
• Cohort genes: 53
• GWAS associations: 108
• ClinVar variants: 403
• Clinical trials: 2,567
• Precision-medicine evidence (CIViC): 14 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

34 prevalence record(s), Orphanet, top 20 (validated / broadest geography first):

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 100 000	3.221	Europe	Validated
Point prevalence	1-5 / 10 000	15	Europe	Validated
Annual incidence	1-9 / 100 000	6.2	United States	Validated
Annual incidence	1-9 / 100 000	6.264	France	Validated
Annual incidence	1-9 / 100 000	2.106	United Kingdom	Validated
Annual incidence	1-9 / 100 000	5.129	Germany	Validated
Annual incidence	1-9 / 100 000	5.212	Spain	Validated
Annual incidence	1-9 / 100 000	9.266	Italy	Validated
Annual incidence	1-5 / 10 000	15	Greece	Validated
Annual incidence	1-9 / 100 000	5	Canada	Validated
Annual incidence	1-9 / 100 000	5	Oceania	Validated
Annual incidence	1-5 / 10 000	12.5	Latin America	Validated
Annual incidence	1-5 / 10 000	35	China	Validated
Annual incidence	1-5 / 10 000	29	Japan	Validated
Annual incidence	1-5 / 10 000	49	Korea, Republic of	Validated
Annual incidence	6-9 / 10 000	99	Mongolia	Validated
Annual incidence	1-5 / 10 000	16	Africa	Validated
Annual incidence	1-9 / 100 000	5.296	Austria	Validated
Annual incidence	1-9 / 100 000	2.275	Belgium	Validated
Annual incidence	1-9 / 100 000	1.697	Bulgaria	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	hepatocellular carcinoma
Mondo ID	MONDO:0007256
EFO	EFO:0000182
MeSH	D006528
OMIM	114550
Orphanet	88673
DOID	DOID:684, DOID:686
ICD-10-CM	C22.0
ICD-11	1294035808
NCIT	C3099
UMLS	C2239176
MedGen	389187
GARD	0016773
MedDRA	10049010
NORD	1907
Is cancer (heuristic)	yes

Also known as: adult hepatoma · adult primary hepatocellular carcinoma · cancer, hepatocellular · carcinoma of liver · carcinoma of liver cells · carcinoma of the liver cells · carcinoma, hepatocellular, malignant · HCC · hepatoblastoma, somatic · hepatocellular adenocarcinoma · hepatocellular cancer · hepatocellular cancer, somatic · hepatocellular carcinoma · hepatocellular carcinoma, childhood type, somatic · hepatocellular carcinoma, somatic · hepatoma · liver carcinoma · liver cell cancer (hepatocellular carcinoma) · liver cell carcinoma · primary carcinoma of liver cells (+1 more)

Data availability: 403 ClinVar variants · 108 GWAS associations (34 studies) · 92 cell lines · 111 intOGen driver records.

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › adenocarcinoma › hepatocellular carcinoma

Related subtypes (63): epididymal adenocarcinoma, rete testis adenocarcinoma, seminal vesicle adenocarcinoma, ethmoid sinus adenocarcinoma, lacrimal gland adenocarcinoma, papillary adenocarcinoma, fallopian tube adenocarcinoma, bladder adenocarcinoma, ovarian adenocarcinoma, trabecular adenocarcinoma, middle ear adenocarcinoma, bile duct adenocarcinoma, granular cell carcinoma, small intestine adenocarcinoma, urethra adenocarcinoma, villous adenocarcinoma, thymus gland adenocarcinoma, nasal cavity adenocarcinoma, ureter adenocarcinoma, adenocarcinoma in situ, gastroesophageal junction adenocarcinoma, maxillary sinus adenocarcinoma, mucinous adenocarcinoma, acinar cell carcinoma, adenoid cystic carcinoma, breast adenocarcinoma, clear cell adenocarcinoma, colorectal adenocarcinoma, endometrioid adenocarcinoma, esophageal adenocarcinoma, gastric adenocarcinoma, lung adenocarcinoma, prostate adenocarcinoma, renal cell carcinoma, signet ring cell carcinoma, cervical adenocarcinoma, serous adenocarcinoma, endometrium adenocarcinoma, sweat gland carcinoma, cystadenocarcinoma, tubular adenocarcinoma, mesonephric adenocarcinoma, scirrhous adenocarcinoma, pancreatic adenocarcinoma, follicular variant thyroid gland papillary carcinoma, gallbladder adenocarcinoma, hepatoid adenocarcinoma, intestinal type adenocarcinoma, micropapillary serous carcinoma, minor salivary gland adenocarcinoma, poorly differentiated thyroid gland carcinoma, salivary gland basal cell adenocarcinoma, submandibular gland adenocarcinoma, sebaceous adenocarcinoma, parathyroid gland carcinoma, pituitary adenocarcinoma, vaginal adenocarcinoma, Paget disease, diffuse type adenocarcinoma, vulvar adenocarcinoma, thyroid gland adenocarcinoma, gastroesophageal adenocarcinoma, adenoacanthoma

Subtypes (8): hepatocellular clear cell carcinoma, aflatoxin-related hepatocellular carcinoma, sclerosing hepatic carcinoma, fibrolamellar hepatocellular carcinoma, liver diffuse large B-cell lymphoma, adult hepatocellular carcinoma, pediatric hepatocellular carcinoma, hepatoblastoma

Genetics & variants

GWAS landscape

108 GWAS associations across 34 studies. Top hits map to 43 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs738408	3e-93	PNPLA3	T	0.55
rs58542926	3e-52	TM6SF2	T	0.61
rs2856723	3e-43	HLA-DQB1 - MTCO3P1	?	2.68
rs12682374	9e-29	PCAT1, CASC8, POU5F1B	?	0.93
rs1219651	1e-25	FGFR2	?	1.09
rs9272105	5e-22	HLA-DQA1	A	1.28
rs2981584	1e-21	FGFR2	?	0.94
rs10908278	3e-21	HNF1B	?	1.06
rs144861591	4e-20	H1-2 - H2BC4	T	0.45
rs2294915	2e-19	PNPLA3	T	1.75
rs9274407	4e-19	HLA-DQB1	?	0.24
rs17401966	2e-18	KIF1B	A	1.64
rs112149573	2e-17	TOX3	?	1.08
rs9275319	3e-17	HLA-DQB1 - MTCO3P1	A	1.49
rs78540526	1e-15	LINC01488 - PNCRNA-D	?	1.13
rs35409710	2e-15	HLA-DQB1	?	1.09
rs7463708	2e-15	PCAT1, PRNCR1, CASC19	?	1.08
rs11651755	1e-14	HNF1B	?	1.06
rs1485995	8e-14	LINC01488	?	0.95
rs3179778	1e-13	HLA-DPA1	A	0.21
rs4089	1e-13	KLHL8 - MIR5705	C	0.21
rs429358	1e-13	APOE	T	0.27
rs9273736	2e-13	HLA-DQB1	?	1.12
rs2976384	3e-13	PSCA, JRK	?	1.07
rs2596542	4e-13	MICA-AS1	A	1.39
rs10069690	7e-13	TERT	T	0.21
rs1110446	9e-13	TRIM31, TRIM31-AS1	?	1.93
rs58489806	3e-12	MAU2	T	1.88
rs2585181	3e-12	PSCA - LY6K	?	1.05
rs2523961	6e-11	MICD, POLR1HASP, POLR1HASP	?	1.91

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90651054	Sato G	2023	43,098	334,343	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90308764	Sato G	2023	29,753	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90651069	Sato G	2023	29,753	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.
GCST90809296	Ghouse J	2025	3,748	1,861,536	Genome-wide meta-analysis identifies nine loci associated with higher risk of hepatocellular carcinoma development.
GCST90809294	Ghouse J	2025	2,792	235,223	Genome-wide meta-analysis identifies nine loci associated with higher risk of hepatocellular carcinoma development.
GCST90809295	Ghouse J	2025	2,792	235,223	Genome-wide meta-analysis identifies nine loci associated with higher risk of hepatocellular carcinoma development.
GCST90013702	Ishigaki K	2020	1,866	195,745	Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.
GCST001603	Li S	2012	1,538	0	GWAS identifies novel susceptibility loci on 6p21.32 and 21q21.3 for hepatocellular carcinoma in chronic hepatitis B virus carriers.
GCST90013741	Ishigaki K	2020	1,384	97,655	Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases.
GCST90308757	Sato G	2023	1,361	150,462	Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	4
Tier 2: splice/UTR	1
Tier 3: regulatory	1
Tier 4: intronic/intergenic	44

MAF distribution

Bucket	Variants
common (>=0.05)	49
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	1

Functional consequences

Consequence	Count
intron_variant	28
intergenic_variant	11
non_coding_transcript_exon_variant	4
missense_variant	3
synonymous_variant	1
stop_gained	1
regulatory_region_variant	1
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs738408	22	43928850	C>A,G,T	0.05	synonymous_variant	PNPLA3	3e-93	Tier 4: intronic/intergenic
rs58542926	19	19268740	C>A,T	0.05	stop_gained	TM6SF2	3e-52	Tier 1: coding
rs2856723	6	32699985	A>G	0.05	intergenic_variant	HLA-DQB1 - MTCO3P1	3e-43	Tier 4: intronic/intergenic
rs12682374	8	127398703	C>A,G,T	0.05	intron_variant	PCAT1, CASC8, POU5F1B	9e-29	Tier 4: intronic/intergenic
rs1219651	10	121584987	G>A,C,T	0.05	intron_variant	FGFR2	1e-25	Tier 4: intronic/intergenic
rs9272105	6	32632222	G>A,T	0.45	intergenic_variant	HLA-DQA1	5e-22	Tier 4: intronic/intergenic
rs2981584	10	121590702	A>C,G,T	0.05	intron_variant	FGFR2	1e-21	Tier 4: intronic/intergenic
rs10908278	17	37739961	A>C,G,T	0.05	intron_variant	HNF1B	3e-21	Tier 4: intronic/intergenic
rs144861591	6	26072764	C>T	0.05	intergenic_variant	H1-2 - H2BC4	4e-20	Tier 4: intronic/intergenic
rs2294915	22	43945024	C>G,T	0.05	intron_variant	PNPLA3	2e-19	Tier 4: intronic/intergenic
rs9274407	6	32665055	A>C,G,T	0.05	missense_variant	HLA-DQB1	4e-19	Tier 1: coding
rs17401966	1	10325413	A>G	0.28	intron_variant	KIF1B	2e-18	Tier 4: intronic/intergenic
rs112149573	16	52547333	G>C,T	0.05	intron_variant	TOX3	2e-17	Tier 4: intronic/intergenic
rs9275319	6	32698518	A>G,T	0.12	intergenic_variant	HLA-DQB1 - MTCO3P1	3e-17	Tier 4: intronic/intergenic
rs78540526	11	69516650	C>T	0.05	regulatory_region_variant	LINC01488 - PNCRNA-D	1e-15	Tier 3: regulatory
rs35409710	6	32661126	G>A	0.05	intron_variant	HLA-DQB1	2e-15	Tier 4: intronic/intergenic
rs7463708	8	127091810	G>A,C,T	0.05	non_coding_transcript_exon_variant	PCAT1, PRNCR1, CASC19	2e-15	Tier 4: intronic/intergenic
rs11651755	17	37739849	T>C	0.05	intron_variant	HNF1B	1e-14	Tier 4: intronic/intergenic
rs1485995	11	69492939	G>A,C	0.05	non_coding_transcript_exon_variant	LINC01488	8e-14	Tier 4: intronic/intergenic
rs3179778	6	33068197	A>G	0.05	intron_variant	HLA-DPA1	1e-13	Tier 4: intronic/intergenic
rs4089	4	87300193	C>G,T	0.05	intergenic_variant	KLHL8 - MIR5705	1e-13	Tier 4: intronic/intergenic
rs429358	19	44908684	T>C	0.05	missense_variant	APOE	1e-13	Tier 1: coding
rs9273736	6	32661595	G>A,C	0.05	intron_variant	HLA-DQB1	2e-13	Tier 4: intronic/intergenic
rs2976384	8	142671576	T>A,C	0.05	intergenic_variant	PSCA, JRK	3e-13	Tier 4: intronic/intergenic
rs2596542	6	31398818	C>A,G,T	0.33	intron_variant	MICA-AS1	4e-13	Tier 4: intronic/intergenic
rs10069690	5	1279675	C>T	0.05	intron_variant	TERT	7e-13	Tier 4: intronic/intergenic
rs1110446	6	30103160	C>A,G,T	0.05	3_prime_UTR_variant	TRIM31, TRIM31-AS1	9e-13	Tier 2: splice/UTR
rs58489806	19	19346108	C>T	0.05	intron_variant	MAU2	3e-12	Tier 4: intronic/intergenic
rs2585181	8	142690296	C>A	0.05	intergenic_variant	PSCA - LY6K	3e-12	Tier 4: intronic/intergenic
rs2523961	6	29971803	G>A,C,T	0.05	non_coding_transcript_exon_variant	MICD, POLR1HASP, POLR1HASP	6e-11	Tier 4: intronic/intergenic

ClinVar germline variants

403 retrieved; paginated sample, class counts are floors:

146 uncertain significance, 124 conflicting classifications of pathogenicity, 50 pathogenic, 27 pathogenic/likely pathogenic, 23 benign/likely benign, 13 likely pathogenic, 12 benign, 5 likely benign, 1 pathogenic/likely pathogenic/pathogenic, low penetrance, 1 pathogenic; other, 1 other

ClinVar	Variant (HGVS)	Gene	Classification	Review
127312	NM_000038.6(APC):c.646C>T (p.Arg216Ter)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
140952	NM_000038.6(APC):c.637C>T (p.Arg213Ter)	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
183078	NM_000038.6(APC):c.3149del (p.Ala1050fs)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
184937	NM_000038.6(APC):c.994C>T (p.Arg332Ter)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
184999	NM_000038.6(APC):c.847C>T (p.Arg283Ter)	APC	Pathogenic	reviewed by expert panel
217924	NM_000038.6(APC):c.1312+3A>G	APC	Pathogenic	reviewed by expert panel
233970	NM_000038.6(APC):c.933+1G>A	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2583948	NM_000038.6(APC):c.423-12A>G	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2584112	NM_000038.6(APC):c.6634dup (p.Gln2212fs)	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3232245	NM_000038.6(APC):c.1380del (p.Glu461fs)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
3892976	NM_000038.6(APC):c.2898dup (p.Val967fs)	APC	Pathogenic	criteria provided, single submitter
3892977	NM_000038.6(APC):c.347del (p.Gly116fs)	APC	Pathogenic	criteria provided, single submitter
3892979	NC_000005.9:g.(?112043173)(112043595_?)del	APC	Pathogenic	criteria provided, single submitter
42248	NM_000038.6(APC):c.694C>T (p.Arg232Ter)	APC	Pathogenic	reviewed by expert panel
433627	NM_000038.6(APC):c.1779G>A (p.Trp593Ter)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
433656	NM_000038.6(APC):c.3901dup (p.Thr1301fs)	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
439408	NM_000038.6(APC):c.834+1G>A	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
449336	NM_000038.6(APC):c.4831C>T (p.Gln1611Ter)	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
470090	NM_000038.6(APC):c.74_75del (p.Gln25fs)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
482288	NM_000038.6(APC):c.645+1G>T	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
487050	NM_000038.6(APC):c.4970dup (p.Ser1658fs)	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
492663	NM_000038.6(APC):c.3527del (p.Pro1176fs)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
545962	NM_000038.6(APC):c.3867T>A (p.Cys1289Ter)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
618532	NM_000038.6(APC):c.4638_4639del (p.Asn1546fs)	APC	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
807	NM_000038.6(APC):c.1660C>T (p.Arg554Ter)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
810	NM_000038.6(APC):c.2805C>A (p.Tyr935Ter)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
814	NM_000038.6(APC):c.643C>T (p.Gln215Ter)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
816	NM_000038.6(APC):c.3927_3931del (p.Glu1309fs)	APC	Pathogenic	reviewed by expert panel
823	NM_000038.6(APC):c.4612_4613del (p.Glu1538fs)	APC	Pathogenic	criteria provided, multiple submitters, no conflicts
840	NM_000038.6(APC):c.1695del (p.Val566fs)	APC	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 167 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
RNASE3	Act	BLCA	CIViC #4767
CD44			CIViC #855
FGF19			CIViC #7909
FGF3			CIViC #1873
JAK1	LoF	ALL,BRCA,MLYM,OVT,PRAD,PROSTATE,STOMACH,UCEC	CIViC #3090
KIF23			CIViC #7502
KRAS	Act	ALL,AML,ANSC,BLADDER,BLCA,BRCA,CEAD,CESC,CHOL,CLLSLL,COAD,COADREAD,DLBCLNOS,EGC,ESCA,ESCC,HCC,LUAD,LUSC,MEL,MGCT,MT,NSCLC,OVT,PAAD,PANCREAS,PAST,PCM,PRAD,PRCC,READ,STAD,STOMACH,UCEC,UCS,WDTC	CIViC #30
NEDD9			CIViC #3852
PROM1			CIViC #7014
TERT	Act	PRCC	CIViC #79
TP53	LoF	ACC,ALL,AML,ANGS,ANSC,BCC,BL,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,EGC,ES,ESCA,ESCC,GB,GBC,GBM,GIST,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LNM,LUAD,LUSC,MBL,MEL,MLYM,MT,NBL,NETNOS,NHL,NPC,NSCLC,OS,OVT,PAAD,PANCREAS,PAST,PCM,PLMESO,PRAD,PRCC,PROSTATE,RCC,READ,SACA,SARCNOS,SCLC,SIC,SKCM,SKIN,SOFT_TISSUE,STAD,STOMACH,THYM,UCEC,UCS,UTUC,VULVA,WDTC,WT	CIViC #45
CASP8	LoF	BCC,BLCA,BRCA,CEAD,CESC,CSCC,HNSC,NHL,NPC,STAD,VULVA	CIViC #761
CDKN2A	LoF	ACYC,BLCA,BRCA,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,GBM,HCC,HNSC,LGGNOS,LUAD,LUSC,MEL,MLYM,NPC,NSCLC,OS,PAAD,PANCREAS,RCC,SKCM,SKIN,STAD,STOMACH,WDTC	CIViC #14
CTNNB1	Act	ACC,COAD,COADREAD,ESCA,HCC,LIHB,LUAD,MBL,MEL,NSCLC,OVT,PAST,PRAD,PROSTATE,RMS,SKIN,SOFT_TISSUE,STAD,UCEC,WT	CIViC #1290
FH			CIViC #1892
HLA-DQA1	Act	PLMESO
APC	LoF	AML,ANSC,CHOL,COAD,COADREAD,CSCC,EGC,ESCA,ESCC,HCC,LUAD,MEL,MT,NETNOS,NSCLC,PRAD,PROSTATE,READ,STAD,STOMACH,UM,VULVA	CIViC #66
PIK3CA	Act	ACYC,ANGS,ANSC,BCC,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,EPM,ESCA,ESCC,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MBL,MGCT,NPC,NSCLC,OVT,PAAD,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,UTUC,VULVA,WDTC	CIViC #37
AXIN1	LoF	ESCA,GBM,HCC
PMS2	ambiguous	HCC	CIViC #4371
RAD50	Act	GBM	CIViC #8032
RET	Act	ANGS,MEL,NSCLC,PGNG,SOFT_TISSUE,WDTC	CIViC #42

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGF3	Orphanet:2791	Otodental syndrome
FGF3	Orphanet:90024	Deafness with labyrinthine aplasia, microtia, and microdontia
FGF3	Orphanet:99806	Oculootodental syndrome
JAK1	Orphanet:574957	Mendelian susceptibility to mycobacterial diseases due to partial JAK1 deficiency
JAK1	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
KIF23	Orphanet:98870	Congenital dyserythropoietic anemia type III
KRAS	Orphanet:1333	Familial pancreatic carcinoma
KRAS	Orphanet:1340	Cardiofaciocutaneous syndrome
KRAS	Orphanet:144	Lynch syndrome
KRAS	Orphanet:146	Differentiated thyroid carcinoma
KRAS	Orphanet:2396	Encephalocraniocutaneous lipomatosis
KRAS	Orphanet:251615	Pilomyxoid astrocytoma
KRAS	Orphanet:2612	Linear nevus sebaceus syndrome
KRAS	Orphanet:268114	RAS-associated autoimmune leukoproliferative disease
KRAS	Orphanet:3339	Oculoectodermal syndrome
KRAS	Orphanet:648	Noonan syndrome
KRAS	Orphanet:86834	Juvenile myelomonocytic leukemia
PROM1	Orphanet:1872	Cone rod dystrophy
PROM1	Orphanet:319640	Retinal macular dystrophy type 2
PROM1	Orphanet:791	Retinitis pigmentosa
PROM1	Orphanet:827	Stargardt disease
SET	Orphanet:178469	Autosomal dominant non-syndromic intellectual disability
SET	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
STAT4	Orphanet:117	Behçet disease
STAT4	Orphanet:536	Systemic lupus erythematosus
STAT4	Orphanet:85408	Rheumatoid factor-negative polyarticular juvenile idiopathic arthritis
STAT4	Orphanet:85410	Oligoarticular juvenile idiopathic arthritis
STAT4	Orphanet:93552	Pediatric systemic lupus erythematosus
TERT	Orphanet:146	Differentiated thyroid carcinoma
TERT	Orphanet:1501	Adrenocortical carcinoma
TERT	Orphanet:1775	Dyskeratosis congenita
TERT	Orphanet:2032	Idiopathic pulmonary fibrosis
TERT	Orphanet:2495	Meningioma
TERT	Orphanet:3322	Hoyeraal-Hreidarsson syndrome
TERT	Orphanet:457246	Clear cell sarcoma of kidney
TERT	Orphanet:618	Familial melanoma
TERT	Orphanet:88	Idiopathic aplastic anemia
TLL1	Orphanet:99103	Atrial septal defect, ostium secundum type
TLL1	Orphanet:99106	Atrial septal defect, ostium primum type
TP53	Orphanet:1333	Familial pancreatic carcinoma
TP53	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
TP53	Orphanet:1501	Adrenocortical carcinoma
TP53	Orphanet:210159	Adult hepatocellular carcinoma
TP53	Orphanet:251576	Gliosarcoma
TP53	Orphanet:251579	Giant cell glioblastoma
TP53	Orphanet:251899	Choroid plexus carcinoma
TP53	Orphanet:2807	Papilloma of choroid plexus
TP53	Orphanet:293199	Pleomorphic rhabdomyosarcoma
TP53	Orphanet:3318	Essential thrombocythemia
TP53	Orphanet:524	Li-Fraumeni syndrome

Cohort genes → proteins

53 cohort genes, 52 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	26
civic_only	9
multi_evidence	18

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNASE3	HGNC:10046	ENSG00000169397	P12724	Eosinophil cationic protein	civic_evidence
CD44	HGNC:1681	ENSG00000026508	P16070	CD44 antigen	civic_evidence
FGF19	HGNC:3675	ENSG00000162344	O95750	Fibroblast growth factor 19	civic_evidence
FGF3	HGNC:3681	ENSG00000186895	P11487	Fibroblast growth factor 3	civic_evidence
JAK1	HGNC:6190	ENSG00000162434	P23458	Tyrosine-protein kinase JAK1	civic_evidence
KIF23	HGNC:6392	ENSG00000137807	Q02241	Kinesin-like protein KIF23	civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	civic_evidence
NEDD9	HGNC:7733	ENSG00000111859	Q14511	Enhancer of filamentation 1	civic_evidence
PROM1	HGNC:9454	ENSG00000007062	O43490	Prominin-1	civic_evidence
SET	HGNC:10760	ENSG00000119335	Q01105	Protein SET	clinvar
STAT4	HGNC:11365	ENSG00000138378	Q14765	Signal transducer and activator of transcription 4	gwas
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	clinvar
TLL1	HGNC:11843	ENSG00000038295	O43897	Tolloid-like protein 1	gwas
TM6SF2	HGNC:11861	ENSG00000213996	Q9BZW4	Transmembrane 6 superfamily member 2	gwas
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	clinvar
C2	HGNC:1248	ENSG00000166278	P06681	Complement C2	gwas
UBE4B	HGNC:12500	ENSG00000130939	O95155	Ubiquitin conjugation factor E4 B	gwas
VDR	HGNC:12679	ENSG00000111424	P11473	Vitamin D3 receptor	clinvar
WNT9A	HGNC:12778	ENSG00000143816	O14904	Protein Wnt-9a	gwas
MRPS11	HGNC:14050	ENSG00000181991	P82912	Small ribosomal subunit protein uS11m	gwas
CASP8	HGNC:1509	ENSG00000064012	Q14790	Caspase-8	clinvar
WNT3A	HGNC:15983	ENSG00000154342	P56704	Protein Wnt-3a	gwas
KIF1B	HGNC:16636	ENSG00000054523	O60333	Kinesin-like protein KIF1B	gwas
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	clinvar
PNPLA3	HGNC:18590	ENSG00000100344	Q9NST1	1-acylglycerol-3-phosphate O-acyltransferase PNPLA3	gwas
EFCAB11	HGNC:20357	ENSG00000140025	Q9BUY7	EF-hand calcium-binding domain-containing protein 11	gwas
SAMM50	HGNC:24276	ENSG00000100347	Q9Y512	Sorting and assembly machinery component 50 homolog	gwas
CTNNB1	HGNC:2514	ENSG00000168036	P35222	Catenin beta-1	clinvar
VEPH1	HGNC:25735	ENSG00000197415	Q14D04	Ventricular zone-expressed PH domain-containing protein homolog 1	gwas
DLC1	HGNC:2897	ENSG00000164741	Q96QB1	Rho GTPase-activating protein 7	gwas
DYSF	HGNC:3097	ENSG00000135636	O75923	Dysferlin	gwas
AGA	HGNC:318	ENSG00000038002	P20933	N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase	gwas
MIR572	HGNC:32828	ENSG00000207716		microRNA 572	gwas
FH	HGNC:3700	ENSG00000091483	P07954	Fumarate hydratase, mitochondrial	clinvar
FZD4	HGNC:4042	ENSG00000174804	Q9ULV1	Frizzled-4	gwas
GLB1	HGNC:4298	ENSG00000170266	P16278	Beta-galactosidase	gwas
GRIK1	HGNC:4579	ENSG00000171189	P39086	Glutamate receptor ionotropic, kainate 1	gwas
HLA-DQA1	HGNC:4942	ENSG00000196735	P01909	HLA class II histocompatibility antigen, DQ alpha 1 chain	gwas
HLA-DQB1	HGNC:4944	ENSG00000179344	P01920	HLA class II histocompatibility antigen, DQ beta 1 chain	gwas
HLA-DRB1	HGNC:4948	ENSG00000196126	P01911	HLA class II histocompatibility antigen, DRB1 beta chain	gwas
IGF2R	HGNC:5467	ENSG00000197081	P11717	Cation-independent mannose-6-phosphate receptor	clinvar
APC	HGNC:583	ENSG00000134982	P25054	Adenomatous polyposis coli protein	clinvar
MET	HGNC:7029	ENSG00000105976	P08581	Hepatocyte growth factor receptor	clinvar
MICA	HGNC:7090	ENSG00000204520	Q29983	MHC class I polypeptide-related sequence A	gwas
NBN	HGNC:7652	ENSG00000104320	O60934	Nibrin	clinvar
PDGFRL	HGNC:8805	ENSG00000104213	Q15198	Platelet-derived growth factor receptor-like protein	clinvar
CDK14	HGNC:8883	ENSG00000058091	O94921	Cyclin-dependent kinase 14	gwas
PGD	HGNC:8891	ENSG00000142657	P52209	6-phosphogluconate dehydrogenase, decarboxylating	gwas
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	clinvar
AXIN1	HGNC:903	ENSG00000103126	O15169	Axin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNASE3	Eosinophil cationic protein	Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity.
CD44	CD44 antigen	Cell-surface receptor that plays a role in cell-cell interactions, cell adhesion and migration, helping them to sense and respond to changes in the tissue microenvironment.
FGF19	Fibroblast growth factor 19	Involved in the suppression of bile acid biosynthesis through down-regulation of CYP7A1 expression, following positive regulation of the JNK and ERK1/2 cascades.
FGF3	Fibroblast growth factor 3	Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation.
JAK1	Tyrosine-protein kinase JAK1	Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway.
KIF23	Kinesin-like protein KIF23	Component of the centralspindlin complex that serves as a microtubule-dependent and Rho-mediated signaling required for the myosin contractile ring formation during the cell cycle cytokinesis.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
NEDD9	Enhancer of filamentation 1	Scaffolding protein which plays a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion.
PROM1	Prominin-1	May play a role in cell differentiation, proliferation and apoptosis.
SET	Protein SET	Multitasking protein, involved in apoptosis, transcription, nucleosome assembly and histone chaperoning.
STAT4	Signal transducer and activator of transcription 4	Transcriptional regulator mainly expressed in hematopoietic cells that plays a critical role in cellular growth, differentiation and immune response.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
TLL1	Tolloid-like protein 1	Protease which processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase.
TM6SF2	Transmembrane 6 superfamily member 2	Regulator of liver fat metabolism influencing triglyceride secretion and hepatic lipid droplet content.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
C2	Complement C2	Precursor of the catalytic component of the C3 and C5 convertase complexes, which are part of the complement pathway, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive i…
UBE4B	Ubiquitin conjugation factor E4 B	Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases.
VDR	Vitamin D3 receptor	Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells.
WNT9A	Protein Wnt-9a	Ligand for members of the frizzled family of seven transmembrane receptors.
CASP8	Caspase-8	Thiol protease that plays a key role in programmed cell death by acting as a molecular switch for apoptosis, necroptosis and pyroptosis, and is required to prevent tissue damage during embryonic development and adulthood.
WNT3A	Protein Wnt-3a	Ligand for members of the frizzled family of seven transmembrane receptors.
KIF1B	Kinesin-like protein KIF1B	Has a plus-end-directed microtubule motor activity and functions as a motor for transport of vesicles and organelles along microtubules.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
PNPLA3	1-acylglycerol-3-phosphate O-acyltransferase PNPLA3	Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and precursor for both triglycerides and gl…
SAMM50	Sorting and assembly machinery component 50 homolog	Plays a crucial role in the maintenance of the structure of mitochondrial cristae and the proper assembly of the mitochondrial respiratory chain complexes.
CTNNB1	Catenin beta-1	Key downstream component of the canonical Wnt signaling pathway.
VEPH1	Ventricular zone-expressed PH domain-containing protein homolog 1	Interacts with TGF-beta receptor type-1 (TGFBR1) and inhibits dissociation of activated SMAD2 from TGFBR1, impeding its nuclear accumulation and resulting in impaired TGF-beta signaling.
DLC1	Rho GTPase-activating protein 7	Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling.
DYSF	Dysferlin	Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion.
AGA	N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase	Cleaves the GlcNAc-Asn bond which joins oligosaccharides to the peptide of asparagine-linked glycoproteins.
FH	Fumarate hydratase, mitochondrial	Catalyzes the reversible stereospecific interconversion of fumarate to L-malate.
FZD4	Frizzled-4	Receptor for Wnt proteins.
GLB1	Beta-galactosidase	Cleaves beta-linked terminal galactosyl residues from gangliosides, glycoproteins, and glycosaminoglycans.
GRIK1	Glutamate receptor ionotropic, kainate 1	Ionotropic glutamate receptor that functions as a cation-permeable ligand-gated ion channel, gated by L-glutamate and the glutamatergic agonist kainic acid.
HLA-DQA1	HLA class II histocompatibility antigen, DQ alpha 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DQB1	HLA class II histocompatibility antigen, DQ beta 1 chain	Binds peptides derived from antigens that access the endocytic route of antigen presenting cells (APC) and presents them on the cell surface for recognition by the CD4 T-cells.
HLA-DRB1	HLA class II histocompatibility antigen, DRB1 beta chain	A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
IGF2R	Cation-independent mannose-6-phosphate receptor	Mediates the transport of phosphorylated lysosomal enzymes from the Golgi complex and the cell surface to lysosomes.
APC	Adenomatous polyposis coli protein	Tumor suppressor.
MET	Hepatocyte growth factor receptor	Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand.
MICA	MHC class I polypeptide-related sequence A	Widely expressed membrane-bound protein which acts as a ligand to stimulate an activating receptor KLRK1/NKG2D, expressed on the surface of essentially all human natural killer (NK), gammadelta T and CD8 alphabeta T-cells.
NBN	Nibrin	Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.
CDK14	Cyclin-dependent kinase 14	Serine/threonine-protein kinase involved in the control of the eukaryotic cell cycle, whose activity is controlled by an associated cyclin.
PGD	6-phosphogluconate dehydrogenase, decarboxylating	Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
AXIN1	Axin-1	Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling.
PMS2	Mismatch repair endonuclease PMS2	Component of the post-replicative DNA mismatch repair system (MMR).
RAD50	DNA repair protein RAD50	Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis.
RET	Proto-oncogene tyrosine-protein kinase receptor Ret	Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN,…

Protein-family classification

Druggable: 19 · Difficult: 7 · Unknown: 27 · Druggable fraction: 0.36

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Antibody/Immunoglobulin	5	2.8×	0.188
Kinase	5	2.6×	0.188
Nuclear receptor	1	7.3×	0.386
Protease	3	2.1×	0.396
Scaffold/PPI	4	1.3×	0.662
Other/Unknown	27	0.9×	0.963
Enzyme (other)	4	0.9×	0.963
Transcription factor	3	0.5×	0.963
GPCR	1	0.5×	0.963

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNASE3	Other/Unknown	no		RNaseA, RNaseA_AS, RNaseA_domain
CD44	Other/Unknown	no		Link_dom, CD44_antigen, C-type_lectin-like/link_sf
FGF19	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF, FGF15/19/21
FGF3	Other/Unknown	no		Fibroblast_GF_fam, IL1/FGF
JAK1	Kinase	yes	2.7.10.2	FERM_domain, Prot_kinase_dom, SH2
KIF23	Other/Unknown	no		Kinesin_motor_dom, Kinesin_motor_CS, P-loop_NTPase
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
NEDD9	Scaffold/PPI	no		SH3_domain, Serine_rich_dom, CAS_C
PROM1	Other/Unknown	no		Prominin
SET	Other/Unknown	no		NAP, NAP-like_sf
STAT4	Transcription factor	no		SH2, STAT, p53-like_TF_DNA-bd_sf
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
TLL1	Protease	yes		EGF-type_Asp/Asn_hydroxyl_site, EGF, CUB_dom
TM6SF2	Other/Unknown	no		EXPERA, TM6SF1-like, TM_Tm6sf1/2
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
C2	Protease	yes		Sushi_SCR_CCP_dom, Trypsin_dom, Peptidase_S1A
UBE4B	Transcription factor	no	2.3.2.27	Ubox_domain, Znf_RING/FYVE/PHD, Ub_conjug_fac_E4_core
VDR	Nuclear receptor	yes		VitD_rcpt, Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt
WNT9A	Other/Unknown	no		Wnt, Wnt9a, Wnt_CS
MRPS11	Other/Unknown	no		Ribosomal_uS11, Ribosomal_uS11_CS, Ribosomal_uS11_sf
CASP8	Enzyme (other)	yes	3.4.22.61	Pept_C14_p20, DED_dom, Pept_C14_p10
WNT3A	Other/Unknown	no		Wnt, Wnt3, Wnt_CS
KIF1B	Scaffold/PPI	no		FHA_dom, Kinesin_motor_dom, PH_domain
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
PNPLA3	Other/Unknown	no		PNPLA_dom, Acyl_Trfase/lysoPLipase, PLPL
EFCAB11	Other/Unknown	no		EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS
SAMM50	Other/Unknown	no		Bac_surfAg_D15, POTRA, D15-like
CTNNB1	Other/Unknown	no		Armadillo, ARM-like, Beta-catenin
VEPH1	Scaffold/PPI	no		PH_domain, PH-like_dom_sf, ARM-type_fold
DLC1	Other/Unknown	no		RhoGAP_dom, SAM, START_lipid-bd_dom
DYSF	Other/Unknown	no		C2_dom, Peroxin/Ferlin, Ferlin_A-domain
AGA	Protease	yes	3.5.1.26	Peptidase_T2, Ntn_hydrolases_N
MIR572	Other/Unknown	no
FH	Enzyme (other)	yes	4.2.1.2	Fumarate_lyase_fam, Fum_hydII, L-Aspartase-like
FZD4	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM
GLB1	Other/Unknown	no		Glycoside_Hdrlase_35, Galactose-bd-like_sf, GH_hydrolase_sf
GRIK1	Other/Unknown	no		Iontro_rcpt_C, Iono_Glu_rcpt_met, ANF_lig-bd_rcpt
HLA-DQA1	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
HLA-DQB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
HLA-DRB1	Antibody/Immunoglobulin	yes		MHC_II_b_N, Ig/MHC_CS, Ig_C1-set
IGF2R	Other/Unknown	no		CIMR_rpt, FN_type2_dom, Man6P_isomerase_rcpt-bd_dom_sf
APC	Other/Unknown	no		Armadillo, APC_rpt, SAMP
MET	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Semap_dom
MICA	Antibody/Immunoglobulin	yes		Ig_C1-set, Ig-like_dom, MHC_I-like_Ag-recog
NBN	Other/Unknown	no		FHA_dom, BRCT_dom, SMAD_FHA_dom_sf
PDGFRL	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
CDK14	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
PGD	Enzyme (other)	yes	1.1.1.44	6PGDH_Gnd/GntZ, 6PGDH_C, 6PGDH_NADP-bd
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
AXIN1	Other/Unknown	no		DIX, Axin_b-cat-bd, RGS

Expression context

Cohort genes with no expression data: 0.

48 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	53
unknown	0

Top tissues across cohort

Tissue	Cohort genes
right lung	5
stromal cell of endometrium	4
calcaneal tendon	4
ventricular zone	4
granulocyte	4
monocyte	4
ganglionic eminence	3
buccal mucosa cell	3
skeletal muscle tissue of rectus abdominis	3
pigmented layer of retina	3
adrenal tissue	3
parotid gland	2
gall bladder	2
primordial germ cell in gonad	2
type B pancreatic cell	2
secondary oocyte	2
lower lobe of lung	2
endometrium epithelium	2
sperm	2
jejunal mucosa	2

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNASE3	147	tissue_specific	marker	trabecular bone tissue, bone marrow, bone marrow cell
CD44	294	ubiquitous	marker	parotid gland, stromal cell of endometrium, mammalian vulva
FGF19	28	tissue_specific	marker	gall bladder, epithelial cell of pancreas, primordial germ cell in gonad
FGF3	23	tissue_specific	yes	cerebellar hemisphere, right hemisphere of cerebellum, cerebellar cortex
JAK1	295	ubiquitous	marker	type B pancreatic cell, skin of hip, calcaneal tendon
KIF23	201	ubiquitous	marker	ventricular zone, secondary oocyte, ganglionic eminence
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
NEDD9	269	ubiquitous	marker	right lung, lower lobe of lung, renal glomerulus
PROM1	252	broad	marker	bronchial epithelial cell, epithelium of bronchus, bronchus
SET	295	ubiquitous	marker	ganglionic eminence, endometrium epithelium, calcaneal tendon
STAT4	201	broad	marker	granulocyte, sperm, middle temporal gyrus
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
TLL1	162	broad	marker	secondary oocyte, buccal mucosa cell, primordial germ cell in gonad
TM6SF2	151	broad	marker	ileal mucosa, jejunal mucosa, duodenum
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
C2	138	ubiquitous	marker	liver, right lobe of liver, placenta
UBE4B	294	ubiquitous	marker	buccal mucosa cell, upper leg skin, hair follicle
VDR	224	ubiquitous	marker	tibia, hair follicle, jejunal mucosa
WNT9A	205	broad	yes	decidua, oocyte, gastrocnemius
MRPS11	281	ubiquitous	marker	apex of heart, mucosa of transverse colon, heart left ventricle
CASP8	252	ubiquitous	marker	monocyte, mononuclear cell, leukocyte
WNT3A	31	tissue_specific	yes	placenta, right lung, upper lobe of left lung
KIF1B	287	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, medial globus pallidus
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
PNPLA3	178	ubiquitous	marker	pigmented layer of retina, buccal mucosa cell, right lobe of liver
EFCAB11	260	ubiquitous	marker	sperm, male germ cell, left testis
SAMM50	292	ubiquitous	marker	endothelial cell, vastus lateralis, skeletal muscle tissue of rectus abdominis
CTNNB1	295	ubiquitous	marker	adrenal tissue, ventricular zone, periodontal ligament
VEPH1	178	ubiquitous	marker	pigmented layer of retina, ventricular zone, kidney epithelium
DLC1	268	ubiquitous	marker	adrenal tissue, lower lobe of lung, sural nerve

Protein interactions among cohort

Intra-cohort edges: 30.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
CTNNB1	15,668
KRAS	14,509
CDKN2A	9,311
CD44	6,810
MET	5,823
TERT	5,717
KIF23	5,382
MRPS11	5,290
JAK1	5,229

Intra-cohort edges

A	B	Sources
AGA	IGF2R	intact
AGA	KIF1B	intact
APC	AXIN1	biogrid_interaction, intact, string_interaction
APC	CTNNB1	intact, string_interaction
AXIN1	CTNNB1	biogrid_interaction, intact, string_interaction
AXIN1	TP53	biogrid_interaction
AXIN1	WNT3A	string_interaction
CD44	FGF3	string_interaction
CD44	MET	string_interaction
CD44	PROM1	string_interaction
CDKN2A	KRAS	string_interaction
CDKN2A	TP53	string_interaction
CDKN2A	UBE4B	intact
CTNNB1	MET	biogrid_interaction
CTNNB1	PROM1	intact, string_interaction
CTNNB1	TERT	string_interaction
CTNNB1	WNT3A	string_interaction
CTNNB1	WNT9A	string_interaction
DYSF	KIF1B	biogrid_interaction, intact
FGF19	TP53	intact
FZD4	WNT3A	string_interaction
HLA-DQA1	HLA-DQB1	biogrid_interaction, intact
JAK1	STAT4	string_interaction
KIF1B	RET	string_interaction
KRAS	PIK3CA	string_interaction
KRAS	TP53	string_interaction
NBN	RAD50	biogrid_interaction, intact, string_interaction
PNPLA3	SAMM50	string_interaction
PNPLA3	TM6SF2	string_interaction
TP53	UBE4B	biogrid_interaction

Structural data

PDB: 42 · AlphaFold-only: 10 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KRAS	P01116	511
TP53	P04637	313
PIK3CA	P42336	135
MET	P08581	130
HLA-DRB1	P01911	108
MRPS11	P82912	75
VDR	P11473	52
JAK1	P23458	51
CTNNB1	P35222	50
CASP8	Q14790	36
RET	P07949	34
APC	P25054	31
HLA-DQA1	P01909	28
IGF2R	P11717	24
TERT	O14746	23
AXIN1	O15169	22
C2	P06681	14
RNASE3	P12724	11
DYSF	O75923	11
FZD4	Q9ULV1	11
GRIK1	P39086	11
HLA-DQB1	P01920	10
MICA	Q29983	10
PMS2	P54278	9
GLB1	P16278	8
DLC1	Q96QB1	7
FH	P07954	7
NBN	O60934	7
CD44	P16070	6
RAD50	Q92878	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TM6SF2	Q9BZW4	91.03
EFCAB11	Q9BUY7	87.38
STAT4	Q14765	86.87
PROM1	O43490	85.68
PDGFRL	Q15198	83.54
WNT9A	O14904	83.18
FGF3	P11487	79.32
VEPH1	Q14D04	73.24
PNPLA3	Q9NST1	71.70
CDK14	O94921	71.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 549. Enrichment computed across 53 evidence-associated genes (44 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 44 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TCF dependent signaling in response to WNT	6	16.1×	1e-03	TERT, WNT9A, WNT3A, CTNNB1, APC, AXIN1
Disassembly of the destruction complex and recruitment of AXIN to the membrane	4	32.4×	0.001	WNT3A, CTNNB1, APC, AXIN1
RAF/MAP kinase cascade	7	9.7×	0.001	FGF19, FGF3, JAK1, KRAS, MET, PIK3CA, RET
Signaling by GSK3beta mutants	3	51.9×	0.001	CTNNB1, APC, AXIN1
CTNNB1 S33 mutants aren’t phosphorylated	3	51.9×	0.001	CTNNB1, APC, AXIN1
CTNNB1 S37 mutants aren’t phosphorylated	3	51.9×	0.001	CTNNB1, APC, AXIN1
CTNNB1 S45 mutants aren’t phosphorylated	3	51.9×	0.001	CTNNB1, APC, AXIN1
CTNNB1 T41 mutants aren’t phosphorylated	3	51.9×	0.001	CTNNB1, APC, AXIN1
Interferon gamma signaling	5	14.3×	0.001	CD44, HLA-DQA1, HLA-DQB1, HLA-DRB1, JAK1
Beta-catenin phosphorylation cascade	3	45.8×	0.002	CTNNB1, APC, AXIN1
Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	3	38.9×	0.003	CDKN2A, CTNNB1, MET
Sensing of DNA Double Strand Breaks	2	86.5×	0.009	NBN, RAD50
MET activates PI3K/AKT signaling	2	86.5×	0.009	MET, PIK3CA
Constitutive Signaling by Aberrant PI3K in Cancer	4	11.5×	0.015	FGF19, FGF3, MET, PIK3CA
Signaling by RNF43 mutants	2	57.7×	0.017	WNT3A, FZD4
RUNX3 regulates p14-ARF	2	51.9×	0.017	CDKN2A, KRAS
Interleukin-21 signaling	2	51.9×	0.017	STAT4, JAK1
Signaling by AXIN mutants	2	47.2×	0.017	APC, AXIN1
Signaling by CTNNB1 phospho-site mutants	2	47.2×	0.017	APC, AXIN1
Signaling by APC mutants	2	47.2×	0.017	APC, AXIN1
Signaling by AMER1 mutants	2	47.2×	0.017	APC, AXIN1
MET activates RAS signaling	2	47.2×	0.017	KRAS, MET
PI3K Cascade	3	18.5×	0.017	FGF19, FGF3, PIK3CA
Signaling by FGFR2 in disease	3	18.1×	0.017	FGF3, KRAS, PIK3CA
Transcriptional Regulation by VENTX	3	18.1×	0.017	TP53, CDKN2A, CTNNB1
Signaling by FGFR4 in disease	2	43.3×	0.019	KRAS, PIK3CA
Interleukin-35 Signalling	2	43.3×	0.019	STAT4, JAK1
HDR through MMEJ (alt-NHEJ)	2	39.9×	0.020	NBN, RAD50
Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants	2	39.9×	0.020	KRAS, PIK3CA
Signaling by PDGFRA extracellular domain mutants	2	39.9×	0.020	KRAS, PIK3CA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 51 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
apoptotic process involved in mammary gland involution	2	220.3×	0.005	VDR, CDKN2A
peptide antigen assembly with MHC class II protein complex	3	62.0×	0.005	HLA-DQA1, HLA-DQB1, HLA-DRB1
replicative senescence	3	58.3×	0.005	TERT, TP53, CDKN2A
positive regulation of execution phase of apoptosis	3	49.6×	0.005	TP53, CASP8, DLC1
canonical Wnt signaling pathway	5	15.0×	0.005	WNT9A, WNT3A, CTNNB1, FZD4, AXIN1
telomeric 3’ overhang formation	2	165.2×	0.006	NBN, RAD50
positive regulation of apoptotic process involved in mammary gland involution	2	165.2×	0.006	VDR, CDKN2A
cytokine-mediated signaling pathway	5	12.8×	0.006	STAT4, CD44, CTNNB1, JAK1, KRAS
cellular response to retinoic acid	4	18.4×	0.006	WNT9A, WNT3A, FZD4, RET
negative regulation of telomere capping	2	132.2×	0.007	NBN, RAD50
liver development	4	17.4×	0.007	IGF2R, KRAS, MET, PIK3CA
antigen processing and presentation of exogenous peptide antigen via MHC class II	3	32.0×	0.008	HLA-DQA1, HLA-DQB1, HLA-DRB1
positive regulation of skeletal muscle tissue development	2	110.1×	0.009	WNT3A, CTNNB1
positive regulation of immune response	3	28.3×	0.010	HLA-DQA1, HLA-DQB1, HLA-DRB1
positive regulation of homotypic cell-cell adhesion	2	94.4×	0.010	CTNNB1, JAK1
negative regulation of cell population proliferation	7	5.8×	0.010	TP53, VDR, WNT9A, CDKN2A, CTNNB1, DLC1, APC
positive regulation of T cell activation	3	26.1×	0.010	HLA-DQA1, HLA-DQB1, HLA-DRB1
negative regulation of cyclin-dependent protein serine/threonine kinase activity	2	82.6×	0.011	CDKN2A, APC
DNA strand resection involved in replication fork processing	2	82.6×	0.011	NBN, RAD50
positive regulation of apoptotic process	6	6.7×	0.011	TP53, CASP8, CDKN2A, CTNNB1, IGF2R, APC
lymphocyte migration into lymphoid organs	2	73.4×	0.013	NEDD9, RET
neuroblast proliferation	3	21.6×	0.014	TP53, CTNNB1, NBN
R-loop processing	2	66.1×	0.014	NBN, RAD50
telomere maintenance via recombination	2	60.1×	0.015	TERT, RAD50
DNA double-strand break processing	2	60.1×	0.015	NBN, RAD50
dorsal/ventral axis specification	2	60.1×	0.015	CTNNB1, AXIN1
somatic stem cell division	2	60.1×	0.015	WNT3A, CDKN2A
homologous recombination	2	55.1×	0.016	NBN, RAD50
myoblast proliferation	2	55.1×	0.016	CTNNB1, KRAS
establishment of blood-brain barrier	2	55.1×	0.016	CTNNB1, FZD4

Therapeutics

Drugs indicated for this disease

1 approved, 79 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Tremelimumab	Approved (phase 4)
Acetazolamide	Phase 3 (in late-stage trials)
Aglatimagene Besadenovec	Phase 3 (in late-stage trials)
Albumin Human	Phase 3 (in late-stage trials)
Aprepitant	Phase 3 (in late-stage trials)
Arginine	Phase 3 (in late-stage trials)
Arginine Hydrochloride	Phase 3 (in late-stage trials)
Aspirin	Phase 3 (in late-stage trials)
Atezolizumab	Phase 3 (in late-stage trials)
Azathioprine	Phase 3 (in late-stage trials)
Benmelstobart	Phase 3 (in late-stage trials)
Bevacizumab	Phase 3 (in late-stage trials)
Brivanib	Phase 3 (in late-stage trials)
CS-1003	Phase 3 (in late-stage trials)
Cabozantinib	Phase 3 (in late-stage trials)
Cadonilimab	Phase 3 (in late-stage trials)
Camrelizumab	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Catequentinib	Phase 3 (in late-stage trials)
Chlorotrianisene	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Cyclosporine	Phase 3 (in late-stage trials)
Dexamethasone	Phase 3 (in late-stage trials)
Dextrose	Phase 3 (in late-stage trials)
Doxorubicin	Phase 3 (in late-stage trials)
Durvalumab	Phase 3 (in late-stage trials)
Epirubicin	Phase 3 (in late-stage trials)
Erlotinib	Phase 3 (in late-stage trials)
Ethiodized Oil	Phase 3 (in late-stage trials)
Fluorouracil	Phase 3 (in late-stage trials)
Gemcitabine	Phase 3 (in late-stage trials)
Granisetron	Phase 3 (in late-stage trials)
Hydroxycamptothecin	Phase 3 (in late-stage trials)
INTERFERON ALFA-2B	Phase 3 (in late-stage trials)
Icaritin	Phase 3 (in late-stage trials)
Interferon Alfa	Phase 3 (in late-stage trials)
Ipilimumab	Phase 3 (in late-stage trials)
Irinotecan	Phase 3 (in late-stage trials)
Lamivudine	Phase 3 (in late-stage trials)
Lenvatinib	Phase 3 (in late-stage trials)
Levamisole	Phase 3 (in late-stage trials)
Linifanib	Phase 3 (in late-stage trials)
Lobaplatin	Phase 3 (in late-stage trials)
Mitomycin	Phase 3 (in late-stage trials)
Mitomycin A	Phase 3 (in late-stage trials)
Muparfostat	Phase 3 (in late-stage trials)
Mycophenolate Mofetil	Phase 3 (in late-stage trials)
Nivolumab	Phase 3 (in late-stage trials)
Octreotide	Phase 3 (in late-stage trials)
Orantinib	Phase 3 (in late-stage trials)
Oxaliplatin	Phase 3 (in late-stage trials)
PEGINTERFERON ALFA-2B	Phase 3 (in late-stage trials)
Pegargiminase	Phase 3 (in late-stage trials)
Pembrolizumab	Phase 3 (in late-stage trials)
Penpulimab	Phase 3 (in late-stage trials)
Pexastimogene Devacirepvec	Phase 3 (in late-stage trials)
Pirarubicin	Phase 3 (in late-stage trials)
Polyethylene Glycol	Phase 3 (in late-stage trials)
Pravastatin	Phase 3 (in late-stage trials)
Prednisolone	Phase 3 (in late-stage trials)
Raltitrexed	Phase 3 (in late-stage trials)
Ramucirumab	Phase 3 (in late-stage trials)
Regorafenib	Phase 3 (in late-stage trials)
Rivoceranib	Phase 3 (in late-stage trials)
Seocalcitol	Phase 3 (in late-stage trials)
Serplulimab	Phase 3 (in late-stage trials)
Sintilimab	Phase 3 (in late-stage trials)
Sirolimus	Phase 3 (in late-stage trials)
Sitravatinib	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Somatostatin	Phase 3 (in late-stage trials)
Sorafenib	Phase 3 (in late-stage trials)
Tacrolimus Anhydrous	Phase 3 (in late-stage trials)
Tenofovir Anhydrous	Phase 3 (in late-stage trials)
Thalidomide	Phase 3 (in late-stage trials)
Thymopentin	Phase 3 (in late-stage trials)
Tiragolumab	Phase 3 (in late-stage trials)
Tislelizumab	Phase 3 (in late-stage trials)
Tivantinib	Phase 3 (in late-stage trials)
Toripalimab	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Abemaciclib, Adagloxad Simolenin, Adebrelimab, Amivantamab, Arsenic Trioxide, Avelumab, Axitinib, Baclofen, Bavituximab, Capecitabine, Capmatinib, Carotuximab, Cetuximab, Dovitinib, Endostatin, Endostatin, N-Terminal-Mggshhhhh, Envafolimab, Enzalutamide, Erfonrilimab, Etodolac, Etoposide, Everolimus, Filgrastim, Finotonlimab, Floxuridine, Fludarabine, Fruquintinib, Futibatinib, Ganciclovir, Gimeracil, Guadecitabine, Hydroxychloroquine, Idarubicin, Ivonescimab, Lanreotide, Lenalidomide, Linsitinib, Lisinopril Anhydrous, Menatetrenone, Metformin, Namodenoson, Nimotuzumab, Nintedanib, Ociperlimab, Oteracil, P-Toluenesulfonamide, PEGINTERFERON ALFA-2A, Paclitaxel, Paclitaxel Docosahexaenoic Acid, Palbociclib, Pasireotide, Patupilone, Perflutren, Pevonedistat, Piflufolastat, Prednisone, Propranolol, Pucotenlimab, Quavonlimab, Relatlimab, Ribociclib, Rilvegostomig, Rituximab, Simvastatin, Sulfur Hexafluoride, Sunitinib, Surufatinib, Tegafur, Temozolomide, Temsirolimus, Tertomotide, Thymalfasin, Tigatuzumab, Tirapazamine, Tivozanib, Trametinib, Trebananib, Ubidecarenone, Uracil, Urea, Vancomycin, Vandetanib, Veliparib, Volrustomig.

Drug target analysis

Approved (phase 4): 12 · Phase ≥3: 14 · Phased (≥1): 18 · Undrugged: 35

Druggability breadth: 34 of 53 evidence-associated genes (64%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
JAK1	FEDRATINIB
KRAS	VEMURAFENIB
TERT	BERBERINE
TP53	NITROFURANTOIN
VDR	CHOLECALCIFEROL
CASP8	PRIMAQUINE PHOSPHATE
CTNNB1	DITHIAZANINE IODIDE
GLB1	MIGALASTAT
MET	AFATINIB
CDK14	FEDRATINIB
PIK3CA	IDELALISIB
RET	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
RET	135	4
MET	95	4
JAK1	68	4
PIK3CA	67	4
CDK14	17	4
KRAS	11	4
TERT	10	4
VDR	10	4
CTNNB1	4	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
FEDRATINIB	4	CDK14, JAK1, MET, PIK3CA, RET
RUXOLITINIB	4	JAK1, RET
TOFACITINIB	4	JAK1, RET
UPADACITINIB	4	JAK1, RET
MOMELOTINIB	4	JAK1
PONATINIB	4	JAK1, RET
RUXOLITINIB PHOSPHATE	4	JAK1
ENTRECTINIB	4	JAK1, MET, RET
PACRITINIB	4	JAK1
TOFACITINIB CITRATE	4	JAK1, RET
BARICITINIB	4	JAK1, RET
CERITINIB	4	JAK1, MET, RET
PEFICITINIB	4	JAK1
FILGOTINIB	4	JAK1
ABROCITINIB	4	JAK1
RITLECITINIB	4	JAK1
DEUCRAVACITINIB	4	JAK1
NINTEDANIB	4	CDK14, JAK1, MET, RET
SUNITINIB	4	CDK14, JAK1, MET, PIK3CA, RET
CRIZOTINIB	4	JAK1, MET, PIK3CA, RET
MIDOSTAURIN	4	JAK1, MET, PIK3CA, RET
VEMURAFENIB	4	KRAS, RET
DABRAFENIB	4	KRAS, MET
LONAFARNIB	4	KRAS
SOTORASIB	4	KRAS
ADAGRASIB	4	KRAS
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 10.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
MET	2,015	Binding:2005, Functional:6, ADMET:4
RET	1,586	Binding:1573, Functional:10, ADMET:3
JAK1	1,502	Binding:1428, Functional:49, ADMET:24, Toxicity:1
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
VDR	561	Binding:459, Functional:99, ADMET:3
TERT	391	Binding:389, Functional:2
CTNNB1	361	Binding:358, Functional:3
CDK14	179	Binding:179
GLB1	124	Binding:123, ADMET:1
CASP8	116	Binding:106, Functional:10
GRIK1	70	Binding:55, Functional:15
WNT3A	31	Binding:31
APC	24	Binding:24
STAT4	20	Binding:20
PGD	19	Binding:19
HLA-DRB1	17	Binding:17
KIF23	15	Binding:15
AXIN1	11	Binding:11
CD44	9	Binding:9
SET	8	Binding:8
FZD4	7	Functional:6, Binding:1
RAD50	7	Binding:7
TLL1	5	Binding:5
IGF2R	5	Binding:4, Functional:1
C2	4	Binding:4
CDKN2A	2	Binding:2
HLA-DQA1	2	Binding:2
NBN	2	Binding:2
KIF1B	1	Binding:1
SAMM50	1	Binding:1
FH	1	Binding:1
MICA	1	Binding:1
PMS2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
JAK1	2.7.10.2	non-specific protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
UBE4B	2.3.2.27, 2.3.2.B12	RING-type E3 ubiquitin transferase,
CASP8	3.4.22.61	caspase-8
AGA	3.5.1.26	N4-(beta-N-acetylglucosaminyl)-L-asparaginase
FH	4.2.1.2	fumarate hydratase
MET	2.7.10.1	receptor protein-tyrosine kinase
PGD	1.1.1.44	phosphogluconate dehydrogenase (NADP+-dependent, decarboxylating)
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
RET	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
JAK1	1,502
KRAS	861
TERT	391
TP53	869
VDR	561
CASP8	116
CTNNB1	361
GLB1	124
MET	2,015
CDK14	179
PIK3CA	2,034
RET	1,586

Pharmacogenomics

Cohort genes with a PharmGKB record: 53; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

30 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
FEDRATINIB	4	CDK14, JAK1, MET, PIK3CA, RET
RUXOLITINIB	4	JAK1, RET
TOFACITINIB	4	JAK1, RET
UPADACITINIB	4	JAK1, RET
MOMELOTINIB	4	JAK1
PONATINIB	4	JAK1, RET
RUXOLITINIB PHOSPHATE	4	JAK1
ENTRECTINIB	4	JAK1, MET, RET
PACRITINIB	4	JAK1
TOFACITINIB CITRATE	4	JAK1, RET
BARICITINIB	4	JAK1, RET
CERITINIB	4	JAK1, MET, RET
PEFICITINIB	4	JAK1
FILGOTINIB	4	JAK1
ABROCITINIB	4	JAK1
RITLECITINIB	4	JAK1
DEUCRAVACITINIB	4	JAK1
NINTEDANIB	4	CDK14, JAK1, MET, RET
SUNITINIB	4	CDK14, JAK1, MET, PIK3CA, RET
CRIZOTINIB	4	JAK1, MET, PIK3CA, RET
MIDOSTAURIN	4	JAK1, MET, PIK3CA, RET
VEMURAFENIB	4	KRAS, RET
DABRAFENIB	4	KRAS, MET
LONAFARNIB	4	KRAS
SOTORASIB	4	KRAS
ADAGRASIB	4	KRAS
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
NITROFURANTOIN	4	TP53
DIOSMIN	4	TP53

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	12	JAK1, KRAS, TERT, TP53, VDR, CASP8, CTNNB1, GLB1, MET, CDK14 (+2 more)
B	Phased (≥1) drug, not yet approved	6	KIF23, SET, WNT3A, GRIK1, PGD, RAD50
C	Druggable family + PDB, no drug	9	TLL1, C2, AGA, FH, FZD4, HLA-DQA1, HLA-DQB1, HLA-DRB1, MICA
D	Druggable family + AlphaFold only, no drug	1	PDGFRL
E	Difficult family or no structure, no drug	25	RNASE3, CD44, FGF19, FGF3, NEDD9, PROM1, STAT4, TM6SF2, UBE4B, WNT9A (+15 more)

Undrugged target profiles

35 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
WNT9A	0	CTNNB1
APC	24	CTNNB1
NBN	2	RAD50
AXIN1	11	CTNNB1
RNASE3	0	—
CD44	9	—
FGF19	0	—
FGF3	0	—
NEDD9	0	—
PROM1	0	—
STAT4	20	—
TLL1	5	—
TM6SF2	0	—
C2	4	—
UBE4B	0	—
MRPS11	0	—
KIF1B	1	—
CDKN2A	2	—
PNPLA3	0	—
EFCAB11	0	—
SAMM50	1	—
VEPH1	0	—
DLC1	0	—
DYSF	0	—
AGA	0	—
MIR572	0	—
FH	1	—
FZD4	7	—
HLA-DQA1	2	—
HLA-DQB1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2,567.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	582
PHASE1/PHASE2	195
PHASE3	192
PHASE4	73
PHASE2/PHASE3	58

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02785380	PHASE4	NOT_YET_RECRUITING	Laparoscopic Surgery VS RFA for Recurrent HCC
NCT03024684	PHASE4	ACTIVE_NOT_RECRUITING	Statin for Preventing Hepatocellular Carcinoma Recurrence After Curative Treatment
NCT04032860	PHASE4	ACTIVE_NOT_RECRUITING	RCT of Different Effects of Nucleot(s)Ide Analogues on the Prognosis of HBV-HCC Patients After Curative Resection
NCT05185505	PHASE4	RECRUITING	Atezolizumab and Bevacizumab Pre-Liver Transplantation for Patients With Hepatocellular Carcinoma Beyond Milan Criteria
NCT05331911	PHASE4	RECRUITING	Impact of Propofol-Based Total Intravenous Anesthesia Versus Anesthesia With Sevoflurane on Long-term Outcomes With Patients Undergoing Elective Excision of Primary Liver Tumors
NCT06311916	PHASE4	NOT_YET_RECRUITING	Efficacy and Safety of Neoadjuvant Therapy in Patients With Resectable HCC Screened by a Multimodal Deep Learning Model.
NCT06311929	PHASE4	RECRUITING	Precision Adjuvant Therapy After Surgery for Hepatocellular Carcinoma
NCT06311942	PHASE4	RECRUITING	Triple vs. Dual Adjuvant Therapy Following Liver Resection for HCC.
NCT06464380	PHASE4	NOT_YET_RECRUITING	Anti-cancer Potentiality of Saffron Against Hepatocellular Carcinoma
NCT06594744	PHASE4	RECRUITING	Endoscopic Variceal Ligation vs Carvedilol for the Prevention of First Esophageal Variceal Bleeding in Patients With HCC
NCT06717919	PHASE4	RECRUITING	HOPE Against Cancer Recurrence in HCC
NCT06923176	PHASE4	NOT_YET_RECRUITING	Effect of Biejia-Ruangan Compound on Survival Rate and Recurrence Rate of Hepatocellular Carcinoma After Radical Treatment
NCT06930573	PHASE4	RECRUITING	A Study of AK112, a PD-1/ VEGF Bispecific Antibody, for Resectable Hepatocellular Carcinoma With High Recurrence Risk
NCT07059494	PHASE4	RECRUITING	Atezolizumab and Bevacizumab in Combination With Y^90 Radioembolization in HCC for Liver Transplant
NCT07150624	PHASE4	RECRUITING	The Treatment of Liver Injury After Liver Resection With Polyene Phosphatidylcholine
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT00168987	PHASE4	COMPLETED	Influence of an Oral Nutritional Supplement Rich in Omega-3 Fatty Acids on Functional State and Quality of Life in Malnourished Patients With Gastroenterological Tumors
NCT00554905	PHASE4	UNKNOWN	Radiofrequency Ablation With or With Transcatheter Arterial Embolization for Hepatocellular Carcinoma
NCT00555334	PHASE4	UNKNOWN	Nucleoid as an Adjuvant Therapy After Radiofrequency Ablation for Hepatocellular Carcinoma
NCT00556803	PHASE4	UNKNOWN	TACE as an Adjuvant Therapy After Radiofrequency Ablation (RFA) for Hepatocellular Carcinoma
NCT00557024	PHASE4	UNKNOWN	Radiotherapy as an Adjuvant Therapy After Radiofrequency Ablation for Hepatocellular Carcinoma
NCT00646100	PHASE4	COMPLETED	Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis
NCT00768157	PHASE4	UNKNOWN	Efficacy of Antiviral Therapy After Radical Resection for Hepatitis B Virus-Related Hepatocellular Carcinoma
NCT00834860	PHASE4	UNKNOWN	Peginterferon Plus Ribavirin for Hepatitis C Patients Concomitant With Hepatocellular Carcinoma
NCT01098760	PHASE4	COMPLETED	Hepatocellular Carcinoma - Advanced Stage - Sorafenib Trial in Taiwanese Patients
NCT01102335	PHASE4	UNKNOWN	Synergistic Treatment for Hepatocellular Carcinoma (HCC) Using Transcatheter Arterial Chemoembolization (TACE) With Anti-hepatitis B Virus (Anti-HBV) Therapy
NCT01203787	PHASE4	COMPLETED	Sorafenib Dose Ramp-Up in Hepatocellular Carcinoma (HCC)
NCT01298284	PHASE4	UNKNOWN	A Trial of EVL\GVS Alone vs. EVL\GVS Combined Propranolol
NCT01332669	PHASE4	COMPLETED	Drug-eluting Bead in Hepatocellular Carcinoma
NCT01351194	PHASE4	UNKNOWN	Radiofrequency Ablation Versus Hepatic Resection for the Treatment of Hepatocellular Carcinomas Smaller Than 2 cm
NCT01409499	PHASE4	COMPLETED	Palliative Treatments for Patients With Advanced Hepatocellular Carcinoma (HCC)
NCT01415063	PHASE4	UNKNOWN	Radiofrequency Ablation Combined With Transcatheter Arterial Chemoembolization Versus Radiofrequency Ablation Alone for Recurrent Hepatocellular Carcinoma
NCT01438437	PHASE4	UNKNOWN	Trial of Ablation of Small Hepatocellular Carcinomas in Patients of Cirrhosis
NCT01451658	PHASE4	UNKNOWN	A Trial of EVL\GVS Alone vs. EVL\GVS Combined Propranolol (S-HCC)
NCT01570075	PHASE4	UNKNOWN	Radiofrequency Ablation Versus Liver Resection for Elderly Patients With Hepatocellular Carcinoma (HCC) Within the Milan Criteria
NCT01575574	PHASE4	COMPLETED	Magnetic Resonance With Gadoxetic Acid for the Diagnosis of Hepatocellular Carcinoma in Patients With Liver Cirrhosis. Evaluation of Its Impact for the Non-invasive Diagnosis
NCT01639703	PHASE4	COMPLETED	Hepatic Xenetix-CT Perfusion
NCT01798160	PHASE4	COMPLETED	Selective Internal Radiation Therapy (SIRT) Versus Transarterial Chemoembolisation (TACE) for the Treatment of Hepatocellular Carcinoma (HCC).
NCT01806740	PHASE4	TERMINATED	DCE-MRI Using Dotarem® in Evaluation of Therapeutic Response to Sorafenib in Patients With Advanced Stage HCC
NCT01849588	PHASE4	TERMINATED	HCV-RNA Kinetics During Sorafenib for Hepatocellular Carcinoma (HCC)

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CHLOROTRIANISENE	4	68
SORAFENIB	4	62
LENVATINIB	4	25
ETHIODIZED OIL	4	13
CABOZANTINIB	4	11
TREMELIMUMAB	4	11
TORIPALIMAB	4	10
ENTECAVIR ANHYDROUS	4	9
PROPRANOLOL	4	9
DURVALUMAB	4	8
TISLELIZUMAB	4	8
LEUCOVORIN	4	7
ATEZOLIZUMAB	4	5
AXITINIB	4	4
EPIRUBICIN	4	4
ARGININE HYDROCHLORIDE	4	3
ERLOTINIB HYDROCHLORIDE	4	3
IPILIMUMAB	4	3
RAMUCIRUMAB	4	3
SIROLIMUS	4	3
SUFENTANIL	4	3
SUNITINIB MALATE	4	3
TEGAFUR	4	3
THALIDOMIDE	4	3
AVELUMAB	4	2
BEVACIZUMAB	4	2
CAPMATINIB	4	2
ELBASVIR	4	2
ESKETAMINE	4	2
LAPATINIB	4	2

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 14 predictive associations from 14 curated evidence items; also 9 prognostic, 1 predisposing.

Molecular subtype	Therapy	Effect	Level	CIViC
FGF19 Overexpression	Fisogatinib	Sensitivity/Response	CIViC B	EID7636
KRAS Mutation	Sorafenib + Refametinib	Sensitivity/Response	CIViC B	EID1642
VEGFC Overexpression	Sunitinib	Sensitivity/Response	CIViC B	EID7987
EGFR Amplification OR EGFR Alteration	Lenvatinib	Resistance	CIViC B	EID12052
PROM1 EXPRESSION	Sorafenib	Resistance	CIViC B	EID926
FGF3 Amplification	Sorafenib	Sensitivity/Response	CIViC C	EID1966
CDK9 Overexpression	Dinaciclib	Sensitivity/Response	CIViC D	EID9312
FGF19 Overexpression	FGFR4 Inhibitor H3B-6527	Sensitivity/Response	CIViC D	EID7518
JAK1 A1086S	Ruxolitinib	Sensitivity/Response	CIViC D	EID10058
JAK1 E483D	Ruxolitinib	Sensitivity/Response	CIViC D	EID10057
JAK1 N451S	Ruxolitinib	Sensitivity/Response	CIViC D	EID10056
JAK1 S703I	Ruxolitinib	Sensitivity/Response	CIViC D	EID1900
RAF1 Amplification	Sorafenib	Sensitivity/Response	CIViC D	EID9113
FGF19 Overexpression	Sorafenib	Resistance	CIViC D	EID7519