Cutaneous melanoma

Summary

Cutaneous melanoma (MONDO:0005012) is a cancer (an umbrella term covering 10 Mondo subtypes) with 75 cohort genes (395 GWAS associations across 25 studies; 32 CIViC-evidence somatic drivers; 1 ClinVar predisposition record) and 188 clinical trials. The dominant Reactome pathway is Melanin biosynthesis (4 cohort genes). Molecularly, BRAF V600E confers sensitivity to Vemurafenib in Skin Melanoma (CIViC Level A); 57 further subtype–drug associations are mapped below. Top therapeutic interventions include aldesleukin, dabrafenib, and trametinib.

At a glance

• Classification: Cancer
• Umbrella term: 10 Mondo subtypes
• Cohort genes: 75
• GWAS associations: 395
• ClinVar variants: 1
• Clinical trials: 188
• Precision-medicine evidence (CIViC): 58 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cutaneous melanoma
Mondo ID	MONDO:0005012
EFO	EFO:0000389
DOID	DOID:8923
ICD-10-CM	C43
NCIT	C3510
SNOMED CT	93655004
UMLS	C0151779
MedGen	57486
Anatomy (UBERON)	UBERON:0000014
Is cancer (heuristic)	yes

Also known as: cutaneous (skin) melanoma · cutaneous melanoma · cutaneous melanoma (disease) · malignant cutaneous melanoma · malignant melanoma (of skin), stage unspecified · malignant melanoma of skin · malignant melanoma of skin stage unspecified · melanoma (disease) of zone of skin · melanoma of skin · melanoma of the skin · skin melanoma · skin, melanoma · zone of skin melanoma · zone of skin melanoma (disease)

Data availability: 1 ClinVar variant · 395 GWAS associations (25 studies) · 1 HPO phenotype · 390 cell lines · 30 intOGen driver records.

Disease family

An umbrella term covering 10 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › integumentary system cancer › skin cancer › cutaneous melanoma

Related subtypes (12): labium majus cancer, labia minora cancer, prepuce cancer, sweat gland cancer, cutaneous ganglioneuroma, skin carcinoma, malignant dermis tumor, skin meningioma, primary cutaneous lymphoma, CD4+/CD56+ hematodermic neoplasm, eyelid cancer, sebaceous gland cancer

Subtypes (10): eyelid melanoma, balloon cell malignant melanoma, nodular malignant melanoma, acral lentiginous melanoma, amelanotic skin melanoma, superficial spreading melanoma, lentigo maligna melanoma, desmoplastic melanoma, spitzoid melanoma, melanoma in congenital melanocytic nevus

Genetics & variants

GWAS landscape

395 GWAS associations across 25 studies. Top hits map to 33 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs12203592	2e-298	IRF4	C	0.36
rs1805007	1e-288	MC1R	C	0.41
rs4904871	2e-278	SLC24A4	A
rs72930659	4e-278	TPCN2	C
rs12448464	3e-262	SPG7	A
rs1126809	4e-199	TYR	G
rs6059655	3e-157	RALY	A	0.31
rs16891982	2e-141	SLC45A2	C	0.61
rs2762461	8e-125	LURAP1L-AS1, TYRP1	G
rs869330	6e-113	MTAP	A
rs871024	2e-104	MTAP	C	0.15
rs75570604	6e-85	FANCA	G
rs6879563	1e-83	ADGRV1	C
rs3851294	2e-82	DSTYK	A
rs7803075	1e-76	LINC-PINT	A
rs1805008	2e-73	MC1R	T	1.37
rs869329	7e-67	MTAP	?
rs185146	2e-66	SLC45A2	C
rs7943603	4e-54	TYR - NOX4	T	0.11
rs935055	2e-47	MTAP	G	0.2
rs520015	1e-43	ZNG1A - DOCK8-AS1	C
rs13178866	1e-43	CLPTM1L	T	1.14
rs10434895	2e-42	AKAP12	A
rs3761444	4e-41	PLA2G6	G
rs12913832	7e-41	HERC2	A	0.11
rs9929606	2e-40	ANKRD11	C	0.09
rs10197246	9e-39	FLACC1, CASP8	T	0.1
rs4911412	2e-38	RPS2P1 - ASIP	A	0.09
rs31490	3e-36	CLPTM1L	G	0.09
rs11532907	2e-34	MTAP	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475577	Verma A	2024	45,274	389,597	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST010302	Landi MT	2020	36,760	375,188	Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility.
GCST010303	Landi MT	2020	36,760	375,188	Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility.
GCST010304	Landi MT	2020	36,760	375,188	Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility.
GCST007505	Duffy DL	2018	12,874	23,203	Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways.
GCST003061	Law MH	2015	12,874	23,203	Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma.
GCST90475578	Verma A	2024	10,468	436,283	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90079092	Backman JD	2021	3,349	70,881	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90083078	Backman JD	2021	3,349	70,881	Exome sequencing and analysis of 454,787 UK Biobank participants.
GCST90041829	Jiang L	2021	2,824	453,524	A generalized linear mixed model association tool for biobank-scale data.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	9
Tier 2: splice/UTR	1
Tier 3: regulatory	1
Tier 4: intronic/intergenic	39

MAF distribution

Bucket	Variants
common (>=0.05)	45
low_freq (0.01-0.05)	3
rare (<0.01)	2
unknown	0

Functional consequences

Consequence	Count
intron_variant	35
missense_variant	8
intergenic_variant	3
splice_region_variant	1
non_coding_transcript_exon_variant	1
stop_gained	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs26722	5	33963765	C>T	0.045	missense_variant	SLC45A2		Tier 1: coding
rs12913832	15	28120472	A>C,G	0.335	intron_variant	HERC2		Tier 4: intronic/intergenic
rs17305573	20	34592348	T>A,C	0.067	intron_variant	PIGU		Tier 4: intronic/intergenic
rs12203592	6	396321	C>G,T	0.16	intron_variant	IRF4	2e-298	Tier 4: intronic/intergenic
rs1805007	16	89919709	C>A,G,T	0.082	missense_variant	MC1R	1e-288	Tier 1: coding
rs4904871	14	92329568	A>G	0.436	intron_variant	SLC24A4	2e-278	Tier 4: intronic/intergenic
rs72930659	11	69105375	C>T	0.105	intron_variant	TPCN2	4e-278	Tier 4: intronic/intergenic
rs12448464	16	89530306	A>C,G,T	0.356	intron_variant	SPG7	3e-262	Tier 4: intronic/intergenic
rs1126809	11	89284793	G>A	0.243	missense_variant	TYR	4e-199	Tier 1: coding
rs6059655	20	34077942	A>G	0.091	intron_variant	RALY	3e-157	Tier 4: intronic/intergenic
rs16891982	5	33951588	C>A,G	0.038	missense_variant	SLC45A2	2e-141	Tier 1: coding
rs2762461	9	12696499	G>A,T	0.446	intron_variant	LURAP1L-AS1, TYRP1	8e-125	Tier 4: intronic/intergenic
rs869330	9	21804618	A>C,G	0.477	intron_variant	MTAP	6e-113	Tier 4: intronic/intergenic
rs871024	9	21803881	C>A,G	0.48	intron_variant	MTAP	2e-104	Tier 4: intronic/intergenic
rs75570604	16	89780269	G>C	0.065	intron_variant	FANCA	6e-85	Tier 4: intronic/intergenic
rs6879563	5	90968046	C>G,T	0.417	intron_variant	ADGRV1	1e-83	Tier 4: intronic/intergenic
rs3851294	1	205161285	A>C,G,T	0.083	missense_variant	DSTYK	2e-82	Tier 1: coding
rs7803075	7	131057307	A>G	0.317	intron_variant	LINC-PINT	1e-76	Tier 4: intronic/intergenic
rs1805008	16	89919736	C>A,T	0.066	missense_variant	MC1R	2e-73	Tier 1: coding
rs869329	9	21804694	A>G,T	0.05	intron_variant	MTAP	7e-67	Tier 4: intronic/intergenic
rs185146	5	33952001	C>A,T	0.102	intron_variant	SLC45A2	2e-66	Tier 4: intronic/intergenic
rs7943603	11	89320219	T>C	0.35	intergenic_variant	TYR - NOX4	4e-54	Tier 4: intronic/intergenic
rs935055	9	21803184	G>C,T	0.491	intron_variant	MTAP	2e-47	Tier 4: intronic/intergenic
rs520015	9	211762	C>A,G,T	0.49	intergenic_variant	ZNG1A - DOCK8-AS1	1e-43	Tier 4: intronic/intergenic
rs13178866	5	1323097	C>A,T	0.446	intron_variant	CLPTM1L	1e-43	Tier 4: intronic/intergenic
rs10434895	6	151256604	A>C,T	0.476	intron_variant	AKAP12	2e-42	Tier 4: intronic/intergenic
rs3761444	22	38184364	G>A,T	0.453	intron_variant	PLA2G6	4e-41	Tier 4: intronic/intergenic
rs9929606	16	89461129	C>A,G,T	0.45	intron_variant	ANKRD11	2e-40	Tier 4: intronic/intergenic
rs10197246	2	201340018	T>A,C,G	0.28	intron_variant	FLACC1, CASP8	9e-39	Tier 4: intronic/intergenic
rs4911412	20	34128629	A>C,G,T	0.31	intergenic_variant	RPS2P1 - ASIP	2e-38	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4505	NM_016180.5(SLC45A2):c.1122= (p.Leu374=)	SLC45A2	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 182 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 4

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
TERT	TERT	GWAS, Orphanet
SLC45A2	SLC45A2	GWAS, Orphanet
POT1	POT1	GWAS, Orphanet
CDKN2B	CDKN2B	GWAS, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
TERT	Act	PRCC	CIViC #79
CCND1	Act	HNSC,PCM,UCEC	CIViC #8
RNASE1	Act	HNSC,MEL,SKCM	CIViC #4753
RNASE3	Act	BLCA	CIViC #4767
BRAF	Act	BLCA,BRCA,CHOL,CLLSLL,COAD,COADREAD,CSCC,DLBCLNOS,GBM,GIST,HGGNOS,LGGNOS,LUAD,MEL,MLYM,NSCLC,OVT,PAST,PCM,PRAD,PRCC,PROSTATE,READ,SACA,SKCM,STAD,UCEC,WDTC	CIViC #5
CDK4	LoF	MEL	CIViC #13
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
SLTM	Act	CCRCC,LGGNOS,LUAD,NSCLC,OS,PRCC,RCC	CIViC #52
EZH2	Act	ALL,AML,DLBCLNOS,ES,MLYM,NHL	CIViC #63
FGFR3	Act	BLADDER,BLCA,HNSC,LUSC,PCM,PLMESO,UTUC	CIViC #23
ALK	Act	BRCA,HCC,NBL,NSCLC,PROSTATE,SCLC	CIViC #1
GNAQ	Act	HCC,NSCLC,SKCM,UM	CIViC #2317
HLA-DRA			CIViC #2622
JAK1	LoF	ALL,BRCA,MLYM,OVT,PRAD,PROSTATE,STOMACH,UCEC	CIViC #3090
JAK2	Act	ALL,AML,BLADDER,BRCA,NSCLC	CIViC #28
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
NF1	LoF	ACC,ALL,AML,ANGS,BLCA,BRCA,CCRCC,CHOL,CLLSLL,COADREAD,GB,GBM,GIST,HCC,HNSC,LGGNOS,LMS,LUAD,LUNG,LUSC,MEL,NBL,NSCLC,OVT,PAST,PGNG,PLMESO,RMS,SKCM,SOFT_TISSUE,STAD,THYM,UCS	CIViC #3867
NRAS	Act	ALL,AML,ANGS,CHOL,CLLSLL,COAD,COADREAD,GBM,HCC,LGGNOS,LUAD,LUSC,MEL,MGCT,NPC,OVT,PCM,PROSTATE,SKCM,THYM,UCEC,WDTC	CIViC #36
B2M	LoF	CESC,DLBCLNOS,HNSC,MEL,MLYM,NHL,NSCLC	CIViC #537
PTEN	LoF	ANGS,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,CHRCC,COADREAD,CSCC,ESCA,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LUAD,LUSC,MBL,MEL,MT,NSCLC,OVT,PANET,PAST,PRAD,PRCC,PROSTATE,RCC,SCLC,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,WDTC	CIViC #41
SETDB1	Act	BRCA,CLLSLL,COAD,HCC,HNSC,PAAD,PLMESO,UCEC
ZFP36L1	Act	BLCA,MLYM	CIViC #625
TAL2	Act	GBM
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
TYR			CIViC #5972
HDAC4	Act	THYM
BACH2			CIViC #14160
CASP8	LoF	BCC,BLCA,BRCA,CEAD,CESC,CSCC,HNSC,NHL,NPC,STAD,VULVA	CIViC #761
POT1	Act	ANGS,CLLSLL,LGGNOS,MEL,SOFT_TISSUE	CIViC #9935
CDH1	LoF	BLCA,BRCA,CSCC,DLBCLNOS,ESCA,STAD	CIViC #888

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
CCND1	Orphanet:29073	Multiple myeloma
CCND1	Orphanet:52416	Mantle cell lymphoma
CCND1	Orphanet:67038	B-cell chronic lymphocytic leukemia
CCND1	Orphanet:892	Von Hippel-Lindau disease
SLC45A2	Orphanet:79435	Oculocutaneous albinism type 4
BRAF	Orphanet:1340	Cardiofaciocutaneous syndrome
BRAF	Orphanet:146	Differentiated thyroid carcinoma
BRAF	Orphanet:251615	Pilomyxoid astrocytoma
BRAF	Orphanet:389	Langerhans cell histiocytosis
BRAF	Orphanet:500	Noonan syndrome with multiple lentigines
BRAF	Orphanet:54595	Craniopharyngioma
BRAF	Orphanet:58017	Classic hairy cell leukemia
BRAF	Orphanet:626	Large/giant congenital melanocytic nevus
BRAF	Orphanet:648	Noonan syndrome
BRAF	Orphanet:840	Syringocystadenoma papilliferum
BRAF	Orphanet:96253	Cushing disease
CDK4	Orphanet:618	Familial melanoma
CDK4	Orphanet:99970	Dedifferentiated liposarcoma
CDK4	Orphanet:99971	Well-differentiated liposarcoma
CDKN2A	Orphanet:1333	Familial pancreatic carcinoma
CDKN2A	Orphanet:1501	Adrenocortical carcinoma
CDKN2A	Orphanet:252206	Melanoma and neural system tumor syndrome
CDKN2A	Orphanet:404560	Familial atypical multiple mole melanoma syndrome
CDKN2A	Orphanet:524	Li-Fraumeni syndrome
CDKN2A	Orphanet:585909	B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2)
CDKN2A	Orphanet:618	Familial melanoma
CDKN2A	Orphanet:99861	Precursor T-cell acute lymphoblastic leukemia
EZH2	Orphanet:3447	Weaver syndrome
FGFR3	Orphanet:15	Achondroplasia
FGFR3	Orphanet:1860	Thanatophoric dysplasia type 1
FGFR3	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR3	Orphanet:251576	Gliosarcoma
FGFR3	Orphanet:251579	Giant cell glioblastoma
FGFR3	Orphanet:35099	Non-syndromic bicoronal craniosynostosis
FGFR3	Orphanet:429	Hypochondroplasia
FGFR3	Orphanet:53271	Muenke syndrome
FGFR3	Orphanet:794	Saethre-Chotzen syndrome
FGFR3	Orphanet:85164	Camptodactyly-tall stature-scoliosis-hearing loss syndrome
FGFR3	Orphanet:85165	Severe achondroplasia-developmental delay-acanthosis nigricans syndrome
FGFR3	Orphanet:93262	Crouzon syndrome-acanthosis nigricans syndrome
FGFR3	Orphanet:93274	Thanatophoric dysplasia type 2

Cohort genes → proteins

75 cohort genes, 74 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	54
gwas_and_clinvar	1
civic_only	18
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gwas,civic_evidence
CCND1	HGNC:1582	ENSG00000110092	P24385	G1/S-specific cyclin-D1	gwas,civic_evidence
SLC45A2	HGNC:16472	ENSG00000164175	Q9UMX9	Membrane-associated transporter protein	gwas,clinvar
RNASE1	HGNC:10044	ENSG00000129538	P07998	Ribonuclease pancreatic	civic_evidence
RNASE3	HGNC:10046	ENSG00000169397	P12724	Eosinophil cationic protein	civic_evidence
BRAF	HGNC:1097	ENSG00000157764	P15056	Serine/threonine-protein kinase B-raf	civic_evidence
CDK4	HGNC:1773	ENSG00000135446	P11802	Cyclin-dependent kinase 4	civic_evidence
CDKN2A	HGNC:1787	ENSG00000147889	P42771	Cyclin-dependent kinase inhibitor 2A	civic_evidence
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	civic_evidence
EZH2	HGNC:3527	ENSG00000106462	Q15910	Histone-lysine N-methyltransferase EZH2	civic_evidence
FGFR3	HGNC:3690	ENSG00000068078	P22607	Fibroblast growth factor receptor 3	civic_evidence
ALK	HGNC:427	ENSG00000171094	Q9UM73	ALK tyrosine kinase receptor	civic_evidence
GNAQ	HGNC:4390	ENSG00000156052	P50148	Guanine nucleotide-binding protein G(q) subunit alpha	civic_evidence
HLA-DRA	HGNC:4947	ENSG00000204287	P01903	HLA class II histocompatibility antigen, DR alpha chain	civic_evidence
JAK1	HGNC:6190	ENSG00000162434	P23458	Tyrosine-protein kinase JAK1	civic_evidence
JAK2	HGNC:6192	ENSG00000096968	O60674	Tyrosine-protein kinase JAK2	civic_evidence
KRAS	HGNC:6407	ENSG00000133703	P01116	GTPase KRas	civic_evidence
NF1	HGNC:7765	ENSG00000196712	P21359	Neurofibromin	civic_evidence
NRAS	HGNC:7989	ENSG00000213281	P01111	GTPase NRas	civic_evidence
B2M	HGNC:914	ENSG00000166710	P61769	Beta-2-microglobulin	civic_evidence
PTEN	HGNC:9588	ENSG00000171862	P60484	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	civic_evidence
SETDB1	HGNC:10761	ENSG00000143379	Q15047	Histone-lysine N-methyltransferase SETDB1	gwas
SLC24A4	HGNC:10978	ENSG00000140090	Q8NFF2	Sodium/potassium/calcium exchanger 4	gwas
ZFP36L1	HGNC:1107	ENSG00000185650	Q07352	mRNA decay activator protein ZFP36L1	gwas
SLK	HGNC:11088	ENSG00000065613	Q9H2G2	STE20-like serine/threonine-protein kinase	gwas
TAL2	HGNC:11557	ENSG00000186051	Q16559	T-cell acute lymphocytic leukemia protein 2	gwas
TERC	HGNC:11727	ENSG00000270141		telomerase RNA component	gwas
TFAP2B	HGNC:11743	ENSG00000008196	Q92481	Transcription factor AP-2-beta	gwas
TP53	HGNC:11998	ENSG00000141510	P04637	Cellular tumor antigen p53	gwas
TYR	HGNC:12442	ENSG00000077498	P14679	Tyrosinase	gwas
TYRP1	HGNC:12450	ENSG00000107165	P17643	5,6-dihydroxyindole-2-carboxylic acid oxidase	gwas
UGT1A10	HGNC:12531	ENSG00000242515	Q9HAW8	UDP-glucuronosyltransferase 1A10	gwas
UGT1A6	HGNC:12538	ENSG00000167165	P19224	UDP-glucuronosyltransferase 1A6	gwas
UGT1A7	HGNC:12539	ENSG00000244122	Q9HAW7	UDP-glucuronosyltransferase 1A7	gwas
UGT1A8	HGNC:12540	ENSG00000242366	Q9HAW9	UDP-glucuronosyltransferase 1A8	gwas
UGT1A9	HGNC:12541	ENSG00000241119	O60656	UDP-glucuronosyltransferase 1A9	gwas
KIAA0930	HGNC:1314	ENSG00000100364	Q6ICG6	Uncharacterized protein KIAA0930	gwas
ATP10A	HGNC:13542	ENSG00000206190	O60312	Phospholipid-transporting ATPase VA	gwas
ATP11A	HGNC:13552	ENSG00000068650	P98196	Phospholipid-transporting ATPase IH	gwas
HDAC4	HGNC:14063	ENSG00000068024	P56524	Histone deacetylase 4	gwas
BACH2	HGNC:14078	ENSG00000112182	Q9BYV9	Transcription regulator protein BACH2	gwas
MCF2L	HGNC:14576	ENSG00000126217	O15068	Guanine nucleotide exchange factor DBS	gwas
DNAJB4	HGNC:14886	ENSG00000162616	Q9UDY4	DnaJ homolog subfamily B member 4	gwas
MYNN	HGNC:14955	ENSG00000085274	Q9NPC7	Myoneurin	gwas
CASP8	HGNC:1509	ENSG00000064012	Q14790	Caspase-8	gwas
PIGU	HGNC:15791	ENSG00000101464	Q9H490	GPI-anchor transamidase component PIGU	gwas
RTEL1	HGNC:15888	ENSG00000258366	Q9NZ71	Regulator of telomere elongation helicase 1	gwas
RALY	HGNC:15921	ENSG00000125970	Q9UKM9	RNA-binding protein Raly	gwas
FHIP2B	HGNC:16492	ENSG00000158863	Q86V87	FHF complex subunit HOOK-interacting protein 2B	gwas
RAPGEF5	HGNC:16862	ENSG00000136237	Q92565	Rap guanine nucleotide exchange factor 5	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
CCND1	G1/S-specific cyclin-D1	Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition.
SLC45A2	Membrane-associated transporter protein	Proton-associated glucose and sucrose transporter.
RNASE1	Ribonuclease pancreatic	Endonuclease that catalyzes the cleavage of RNA on the 3’ side of pyrimidine nucleotides.
RNASE3	Eosinophil cationic protein	Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity.
BRAF	Serine/threonine-protein kinase B-raf	Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus.
CDK4	Cyclin-dependent kinase 4	Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition.
CDKN2A	Cyclin-dependent kinase inhibitor 2A	Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6.
SLTM	SAFB-like transcription modulator	When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.
EZH2	Histone-lysine N-methyltransferase EZH2	Catalytic subunit of the PRC2/EED-EZH2 complex, a Polycomb group (PcG) complex that methylates ‘Lys-9’ (H3K9me) and ‘Lys-27’ (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene.
FGFR3	Fibroblast growth factor receptor 3	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis.
ALK	ALK tyrosine kinase receptor	Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system.
GNAQ	Guanine nucleotide-binding protein G(q) subunit alpha	Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.
HLA-DRA	HLA class II histocompatibility antigen, DR alpha chain	An alpha chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule.
JAK1	Tyrosine-protein kinase JAK1	Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway.
JAK2	Tyrosine-protein kinase JAK2	Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications.
KRAS	GTPase KRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
NF1	Neurofibromin	Stimulates the GTPase activity of Ras.
NRAS	GTPase NRas	Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
B2M	Beta-2-microglobulin	Component of the class I major histocompatibility complex (MHC).
PTEN	Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN	Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins.
SETDB1	Histone-lysine N-methyltransferase SETDB1	Histone methyltransferase that specifically trimethylates ‘Lys-9’ of histone H3 (H3K9me3).
SLC24A4	Sodium/potassium/calcium exchanger 4	Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+).
ZFP36L1	mRNA decay activator protein ZFP36L1	Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthes…
SLK	STE20-like serine/threonine-protein kinase	Mediates apoptosis and actin stress fiber dissolution.
TFAP2B	Transcription factor AP-2-beta	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
TP53	Cellular tumor antigen p53	Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.
TYR	Tyrosinase	This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds.
TYRP1	5,6-dihydroxyindole-2-carboxylic acid oxidase	Plays a role in melanin biosynthesis.
UGT1A10	UDP-glucuronosyltransferase 1A10	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
UGT1A6	UDP-glucuronosyltransferase 1A6	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to facilitate their inactivation and excretion from the body.
UGT1A7	UDP-glucuronosyltransferase 1A7	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
UGT1A8	UDP-glucuronosyltransferase 1A8	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
UGT1A9	UDP-glucuronosyltransferase 1A9	UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite’s water solubility, thereby facilitating excretion into eit…
ATP10A	Phospholipid-transporting ATPase VA	Catalytic component of P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of phosphatidylcholine (PC) from the outer to the inner leaflet of the plasma membrane.
ATP11A	Phospholipid-transporting ATPase IH	Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of t…
HDAC4	Histone deacetylase 4	Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
BACH2	Transcription regulator protein BACH2	Transcriptional regulator that acts as a repressor or activator.
MCF2L	Guanine nucleotide exchange factor DBS	Guanine nucleotide exchange factor that catalyzes guanine nucleotide exchange on RHOA and CDC42, and thereby contributes to the regulation of RHOA and CDC42 signaling pathways.
DNAJB4	DnaJ homolog subfamily B member 4	Probable chaperone.
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.
PIGU	GPI-anchor transamidase component PIGU	Component of the glycosylphosphatidylinositol-anchor (GPI-anchor) transamidase (GPI-T) complex that catalyzes the formation of the linkage between a proprotein and a GPI-anchor and participates in GPI anchored protein biosynthesis.
RTEL1	Regulator of telomere elongation helicase 1	A probable ATP-dependent DNA helicase implicated in telomere-length regulation, DNA repair and the maintenance of genomic stability.
RALY	RNA-binding protein Raly	RNA-binding protein that acts as a transcriptional cofactor for cholesterol biosynthetic genes in the liver.
FHIP2B	FHF complex subunit HOOK-interacting protein 2B	Able to activate MAPK/ERK and TGFB signaling pathways.
RAPGEF5	Rap guanine nucleotide exchange factor 5	Guanine nucleotide exchange factor (GEF) for RAP1A, RAP2A and MRAS/M-Ras-GTP.
SYNE2	Nesprin-2	Multi-isomeric modular protein which forms a linking network between organelles and the actin cytoskeleton to maintain the subcellular spatial organization.
ZNG1A	Zinc-regulated GTPase metalloprotein activator 1A	Zinc chaperone that directly transfers zinc cofactor to target metalloproteins, thereby activating them.
POT1	Protection of telomeres protein 1	Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini.
CDH1	Cadherin-1	Cadherins are calcium-dependent cell adhesion proteins.

Protein-family classification

Druggable: 26 · Difficult: 15 · Unknown: 34 · Druggable fraction: 0.35

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
Kinase	8	3.0×	0.039
Enzyme (other)	13	2.1×	0.039
Ion channel	1	1.5×	0.799
Scaffold/PPI	5	1.1×	0.799
Phosphatase	1	1.1×	0.799
Transcription factor	10	1.1×	0.799
Transporter	1	1.0×	0.799
Antibody/Immunoglobulin	2	0.8×	0.824
Other/Unknown	34	0.8×	0.974

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
CCND1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
SLC45A2	Transporter	yes		MFS, MFS_trans_sf
RNASE1	Enzyme (other)	yes	4.6.1.18	RNaseA, RNaseA_AS, RNaseA_domain
RNASE3	Other/Unknown	no		RNaseA, RNaseA_AS, RNaseA_domain
BRAF	Kinase	yes	2.7.10.2	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, PKC_DAG/PE
CDK4	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
CDKN2A	Scaffold/PPI	no		Ankyrin_rpt-contain_sf, Ank_Repeat/CDKN_Inhibitor, Tumor_suppres_ARF
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf
EZH2	Enzyme (other)	yes	2.1.1.356	SANT/Myb, SET_dom, EZH1/EZH2_N
FGFR3	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
ALK	Kinase	yes	2.7.10.1	Prot_kinase_dom, MAM_dom, Ser-Thr/Tyr_kinase_cat_dom
GNAQ	Other/Unknown	no		Gprotein_alpha_Q, Gprotein_alpha_su, GproteinA_insert
HLA-DRA	Antibody/Immunoglobulin	yes		MHC_II_a_N, Ig/MHC_CS, Ig_C1-set
JAK1	Kinase	yes	2.7.10.2	FERM_domain, Prot_kinase_dom, SH2
JAK2	Kinase	yes	2.7.10.2	FERM_domain, Prot_kinase_dom, SH2
KRAS	Enzyme (other)	yes	3.6.5.2	Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
NF1	Other/Unknown	no		CRAL-TRIO_dom, RasGAP_dom, Rho_GTPase_activation_prot
NRAS	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Small_GTPase_Ras-type
B2M	Antibody/Immunoglobulin	yes		Ig/MHC_CS, Ig_C1-set, Ig-like_dom
PTEN	Phosphatase	yes	3.1.3.16	Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom
SETDB1	Enzyme (other)	yes	2.1.1.355	SET_dom, Methyl_CpG_DNA-bd, Tudor
SLC24A4	Other/Unknown	no		K/Na/Ca-exchanger, NaCa_Exmemb, NCX_ion-bd_dom_sf
ZFP36L1	Transcription factor	no		Znf_CCCH, Tis11B_N, Znf_CCCH_sf
SLK	Kinase	yes		Prot_kinase_dom, UVR_dom, Ser/Thr_kinase_AS
TAL2	Transcription factor	no		bHLH_dom, HLH_DNA-bd_sf, TAL-like
TERC	Other/Unknown	no
TFAP2B	Transcription factor	no		TF_AP2, TF_AP2_beta, TF_AP2_C
TP53	Transcription factor	no		p53_tumour_suppressor, p53-like_TF_DNA-bd_sf, p53_tetrameristn
TYR	Enzyme (other)	yes	1.14.18.1	Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
TYRP1	Other/Unknown	no		Tyrosinase_Cu-bd, Di-copper_centre_dom_sf, Tyrosinase/Hemocyanin
UGT1A10	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A6	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A7	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A8	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
UGT1A9	Enzyme (other)	yes	2.4.1.17	UDP_glucos_trans, UDP_glycos_trans_CS, UDP-glycosyltransferase
KIAA0930	Other/Unknown	no		DUF2045
ATP10A	Transcription factor	no	7.6.2.1	P_typ_ATPase, P-type_ATPase_IV, ATPase_P-typ_transduc_dom_A_sf
ATP11A	Transcription factor	no	7.6.2.1	P_typ_ATPase, P-type_ATPase_IV, ATPase_P-typ_transduc_dom_A_sf
HDAC4	Enzyme (other)	yes	3.5.1.98	HDACs, Ureohydrolase_dom_sf, His_deacetylse_dom
BACH2	Transcription factor	no		BTB/POZ_dom, bZIP_Maf, bZIP
MCF2L	Scaffold/PPI	no		DH_dom, CRAL-TRIO_dom, GDS_CDC24_CS
DNAJB4	Other/Unknown	no		DnaJ_domain, DnaJ_C, HSP40/DnaJ_pept-bd
MYNN	Transcription factor	no		BTB/POZ_dom, SKP1/BTB/POZ_sf, Znf_C2H2_type
CASP8	Enzyme (other)	yes	3.4.22.61	Pept_C14_p20, DED_dom, Pept_C14_p10
PIGU	Other/Unknown	no		PIG-U
RTEL1	Other/Unknown	no		Helicase-like_DEXD_c2, ATP-dep_Helicase_C, RAD3-like_helicase_DEAD
RALY	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, hnRNP_C
FHIP2B	Other/Unknown	no		FHIP, FHIP_KELAA_motif, FHIP_C
RAPGEF5	Other/Unknown	no		Ras-like_Gua-exchang_fac_N, RASGEF_cat_dom, Ras-like_GEF

Expression context

Cohort genes with no expression data: 0.

70 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)	75
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	10
ganglionic eminence	8
monocyte	8
male germ line stem cell (sensu Vertebrata) in testis	7
sural nerve	7
ventricular zone	6
leukocyte	6
secondary oocyte	5
stromal cell of endometrium	4
pigmented layer of retina	4
buccal mucosa cell	4
endothelial cell	4
skeletal muscle tissue of biceps brachii	4
mucosa of transverse colon	4
upper arm skin	3
bone marrow cell	3
colonic epithelium	3
embryo	3
upper leg skin	3
gingival epithelium	3

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
CCND1	280	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, upper arm skin
SLC45A2	100	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, pigmented layer of retina, primordial germ cell in gonad
RNASE1	283	broad	marker	left testis, right testis, right lung
RNASE3	147	tissue_specific	marker	trabecular bone tissue, bone marrow, bone marrow cell
BRAF	265	ubiquitous	marker	buccal mucosa cell, colonic epithelium, calcaneal tendon
CDK4	138	ubiquitous	marker	embryo, ganglionic eminence, ventricular zone
CDKN2A	220	ubiquitous	marker	parotid gland, cervix squamous epithelium, pituitary gland
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia
EZH2	216	ubiquitous	marker	ganglionic eminence, ventricular zone, embryo
FGFR3	262	broad	marker	upper leg skin, skin of hip, upper arm skin
ALK	181	broad	marker	sperm, male germ cell, male germ line stem cell (sensu Vertebrata) in testis
GNAQ	302	ubiquitous	marker	CA1 field of hippocampus, dorsal motor nucleus of vagus nerve, postcentral gyrus
HLA-DRA	132	broad	marker	monocyte, leukocyte, vermiform appendix
JAK1	295	ubiquitous	marker	type B pancreatic cell, skin of hip, calcaneal tendon
JAK2	272	ubiquitous	marker	calcaneal tendon, monocyte, blood vessel layer
KRAS	298	ubiquitous	marker	trigeminal ganglion, pylorus, nipple
NF1	283	ubiquitous	marker	colonic epithelium, calcaneal tendon, adrenal tissue
NRAS	278	ubiquitous	marker	gingival epithelium, epithelium of nasopharynx, secondary oocyte
B2M	134	ubiquitous	marker	granulocyte, monocyte, leukocyte
PTEN	256	ubiquitous	marker	sperm, endothelial cell, calcaneal tendon
SETDB1	269	ubiquitous	marker	sural nerve, monocyte, mononuclear cell
SLC24A4	168	broad	marker	monocyte, leukocyte, primary visual cortex
ZFP36L1	289	ubiquitous	marker	mucosa of paranasal sinus, endocervix, mucosa of stomach
SLK	293	ubiquitous	marker	esophagus squamous epithelium, endothelial cell, amniotic fluid
TAL2	138		yes	kidney epithelium, skeletal muscle tissue of rectus abdominis, skeletal muscle tissue of biceps brachii
TERC	113	ubiquitous	yes	bone marrow cell, colonic epithelium, male germ line stem cell (sensu Vertebrata) in testis
TFAP2B	128	broad	marker	corpus epididymis, cauda epididymis, oocyte
TP53	223	ubiquitous	marker	ventricular zone, ganglionic eminence, tendon of biceps brachii
TYR	59	tissue_specific	marker	pigmented layer of retina, male germ line stem cell (sensu Vertebrata) in testis, upper leg skin

Protein interactions among cohort

Intra-cohort edges: 64.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TP53	22,736
KRAS	14,509
PTEN	11,626
EZH2	9,646
CDKN2A	9,311
CDH1	8,738
CDK4	8,412
CCND1	8,328
NRAS	7,598
BRAF	7,394

Intra-cohort edges

A	B	Sources
AGR3	CASP8	biogrid_interaction
ALK	KRAS	string_interaction
ALK	NRAS	string_interaction
BRAF	CDKN2A	string_interaction
BRAF	KRAS	biogrid_interaction, intact, string_interaction
BRAF	NF1	string_interaction
BRAF	NRAS	biogrid_interaction, intact, string_interaction
BRAF	PTEN	biogrid_interaction, string_interaction
BRAF	TP53	string_interaction
CCND1	CDK4	biogrid_interaction, intact, string_interaction
CCND1	CDKN2A	biogrid_interaction, string_interaction
CCND1	CDKN2B	string_interaction
CCND1	TP53	string_interaction
CDH1	CDH3	biogrid_interaction, string_interaction
CDH1	MYNN	intact
CDH1	PTEN	string_interaction
CDK4	CDKN2A	biogrid_interaction, intact, string_interaction
CDK4	CDKN2B	biogrid_interaction, intact, string_interaction
CDK4	SETDB1	intact
CDKAL1	CDKN2B	string_interaction
CDKAL1	NRAS	intact
CDKN2A	CDKN2B	biogrid_interaction
CDKN2A	KRAS	string_interaction
CDKN2A	TP53	string_interaction
CDKN2B	TP53	string_interaction
DNAJB4	TUBB3	intact
DOCK8	ZNG1A	string_interaction
EZH2	FGFR3	intact
FGFR3	HSD17B12	intact
JAK1	JAK2	intact, string_interaction
KRAS	NF1	string_interaction
KRAS	NRAS	intact
KRAS	PTEN	string_interaction
KRAS	TP53	string_interaction
MCF2L	SLK	biogrid_interaction
NF1	NRAS	string_interaction
NF1	PTEN	biogrid_interaction, string_interaction
NF1	TP53	string_interaction
NRAS	PIGU	intact
NRAS	PTEN	string_interaction
NRAS	TP53	string_interaction
POT1	TERT	string_interaction
POT1	ZFP36L1	intact
PTEN	TP53	string_interaction
RTEL1	TERT	string_interaction
SETDB1	TFAP2B	intact
SLC24A4	SLC45A2	string_interaction
SLC24A4	TPCN2	string_interaction
SLC24A4	TYR	string_interaction
SLC24A4	TYRP1	string_interaction

Structural data

PDB: 46 · AlphaFold-only: 28 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
B2M	P61769	1,226
KRAS	P01116	511
TP53	P04637	313
JAK2	O60674	164
HLA-DRA	P01903	140
BRAF	P15056	131
ALK	Q9UM73	79
JAK1	P23458	51
EZH2	Q15910	38
GNAQ	P50148	37
CASP8	Q14790	36
NRAS	P01111	35
TUBB3	Q13509	28
NF1	P21359	26
SETDB1	Q15047	26
TERT	O14746	23
CDH1	P12830	22
HDAC4	P56524	19
CDH3	P22223	19
CDK4	P11802	15
FGFR3	P22607	15
POT1	Q9NUX5	14
TYRP1	P17643	13
RNASE1	P07998	12
PTEN	P60484	12
CCND1	P24385	11
RNASE3	P12724	11
SLK	Q9H2G2	7
CDKN2A	P42771	5
TTC7B	Q86TV6	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
HSD17B12	Q53GQ0	94.55
UGT1A9	O60656	92.26
UGT1A10	Q9HAW8	92.11
UGT1A7	Q9HAW7	91.76
UGT1A8	Q9HAW9	91.56
UGT1A6	P19224	91.50
CDKN2B	P42772	90.12
XPO4	Q9C0E2	88.96
CDK10	Q15131	86.27
RASA3	Q14644	84.79
ATP11A	P98196	83.48
DNAJB4	Q9UDY4	83.43
CDKAL1	Q5VV42	82.72
ANO9	A1A5B4	80.99
FHIP2B	Q86V87	80.32
TAL2	Q16559	79.17
SLC45A2	Q9UMX9	77.96
MCF2L	O15068	77.32
CHODL	Q9H9P2	76.83
SLC24A5	Q71RS6	76.63
ZNG1A	Q9BRT8	75.97
DOCK8	Q8NF50	75.17
KIAA0930	Q6ICG6	72.95
ATP10A	O60312	71.30
SLC24A4	Q8NFF2	70.84
SLTM	Q9NWH9	52.38
CDKN2A-AS1	Q9UH64	49.21
TASOR2	Q5VWN6	40.57

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 711. Enrichment computed across 159 evidence-associated genes (100 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 100 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Melanin biosynthesis	4	91.4×	2e-05	SLC45A2, TYR, TYRP1, OCA2
Glucuronidation	5	38.1×	5e-05	UGT1A10, UGT1A6, UGT1A7, UGT1A8, UGT1A9
RUNX3 regulates p14-ARF	4	45.7×	3e-04	CCND1, HDAC4, CDKN2A, KRAS
G1 Phase	5	19.7×	8e-04	CCND1, CDK4, CDKN2A, CDKN2B, JAK2
Erythropoietin activates RAS	4	30.4×	1e-03	RAPGEF1, JAK2, KRAS, NRAS
RAF activation	5	16.8×	0.001	BRAF, JAK2, KRAS, MARK3, NRAS
Translocation of ZAP-70 to Immunological synapse	4	25.4×	0.001	HLA-DQA1, HLA-DQB2, HLA-DRA, HLA-DRB1
Interferon gamma signaling	7	8.8×	0.001	HLA-DQA1, HLA-DQB2, HLA-DRA, HLA-DRB1, JAK1, JAK2, B2M
RAS signaling downstream of NF1 loss-of-function variants	3	48.9×	0.002	KRAS, NF1, NRAS
SUMOylation of transcription factors	4	22.8×	0.002	TFAP2B, TP53, CDKN2A, MITF
Signaling by RAF1 mutants	5	13.9×	0.002	BRAF, JAK2, KRAS, MARK3, NRAS
MITF-M-regulated melanocyte development	7	8.0×	0.002	TERT, CCND1, CDH1, CDKN2A, MARK3, MC1R, MITF
Phosphorylation of CD3 and TCR zeta chains	4	21.8×	0.002	HLA-DQA1, HLA-DQB2, HLA-DRA, HLA-DRB1
Co-inhibition by PD-1	4	20.8×	0.002	HLA-DQA1, HLA-DQB2, HLA-DRA, HLA-DRB1
Signaling by moderate kinase activity BRAF mutants	5	12.7×	0.002	BRAF, JAK2, KRAS, MARK3, NRAS
Paradoxical activation of RAF signaling by kinase inactive BRAF	5	12.7×	0.002	BRAF, JAK2, KRAS, MARK3, NRAS
Signaling downstream of RAS mutants	5	12.7×	0.002	BRAF, JAK2, KRAS, MARK3, NRAS
Cyclin D associated events in G1	5	11.7×	0.003	CCND1, CDK4, CDKN2A, CDKN2B, JAK2
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4	2	114.2×	0.003	CDK4, CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4	2	114.2×	0.003	CDK4, CDKN2A
Cell Cycle	11	4.0×	0.003	TERT, CCND1, RTEL1, SYNE2, CDK4, CDKN2A, CDKN2B, TUBB3 (+3 more)
Diseases of Cellular Senescence	2	76.1×	0.005	CDK4, CDKN2A
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects	2	76.1×	0.005	CDK4, CDKN2A
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	2	76.1×	0.005	CDK4, CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects	2	76.1×	0.005	CDK4, CDKN2A
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	2	76.1×	0.005	CDK4, CDKN2A
Diseases of cellular response to stress	2	76.1×	0.005	CDK4, CDKN2A
Signaling by RAS GAP mutants	2	76.1×	0.005	KRAS, NRAS
Signaling by RAS GTPase mutants	2	76.1×	0.005	KRAS, NRAS
Generation of second messenger molecules	4	13.8×	0.005	HLA-DQA1, HLA-DQB2, HLA-DRA, HLA-DRB1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 132 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
flavone metabolic process	4	510.7×	0e+00	UGT1A10, UGT1A7, UGT1A8, UGT1A9
toxin catabolic process	2	255.3×	0e+00	UGT1A10, UGT1A7
negative regulation of fatty acid metabolic process	5	159.6×	0e+00	UGT1A10, UGT1A6, UGT1A7, UGT1A8, UGT1A9
melanin biosynthetic process	7	68.7×	8e-10	TYR, TYRP1, SLC24A5, MFSD12, MC1R, ASIP, OCA2
peptide antigen assembly with MHC class II protein complex	5	39.9×	3e-05	HLA-DQA1, HLA-DQB2, HLA-DRA, HLA-DRB1, B2M
melanin biosynthetic process from tyrosine	3	95.8×	3e-04	SLC45A2, TYR, OCA2
positive regulation of melanin biosynthetic process	4	42.6×	3e-04	TYRP1, CDH3, MC1R, ASIP
liver development	7	11.8×	3e-04	UGT1A10, UGT1A7, UGT1A8, UGT1A9, JARID2, KRAS, NF1
antigen processing and presentation of exogenous peptide antigen via MHC class II	5	20.6×	5e-04	HLA-DQA1, HLA-DQB2, HLA-DRA, HLA-DRB1, B2M
Ras protein signal transduction	7	10.9×	5e-04	TP53, RAPGEF5, CDKN2A, RAPGEF1, KRAS, NF1, NRAS
replicative senescence	4	30.0×	8e-04	TERT, TP53, CDKN2A, ATM
positive regulation of immune response	5	18.2×	8e-04	HLA-DQA1, HLA-DQB2, HLA-DRA, HLA-DRB1, B2M
positive regulation of T cell activation	5	16.8×	0.001	HLA-DQA1, HLA-DQB2, HLA-DRA, HLA-DRB1, B2M
negative regulation of melanin biosynthetic process	3	54.7×	0.001	SLC24A5, MFSD12, ASIP
flavonoid metabolic process	3	47.9×	0.002	UGT1A7, UGT1A8, UGT1A9
xenobiotic metabolic process	7	7.9×	0.002	UGT1A10, UGT1A6, UGT1A7, UGT1A8, UGT1A9, CYP1B1, AHR
antigen processing and presentation of endogenous peptide antigen via MHC class II	2	127.7×	0.004	HLA-DRA, HLA-DRB1
glucuronate metabolic process	2	127.7×	0.004	UGT1A10, UGT1A6
xenobiotic catabolic process	4	17.0×	0.006	UGT1A10, UGT1A7, CYP1B1, ACSL1
positive regulation of cellular senescence	3	29.5×	0.008	TP53, KRAS, B2M
positive regulation of neuron apoptotic process	5	10.3×	0.008	TFAP2B, TP53, CASP8, NF1, ATM
telomere maintenance	5	10.1×	0.008	TERT, RTEL1, STN1, PARP1, ATM
type II interferon-mediated signaling pathway	3	27.4×	0.009	TP53, JAK1, JAK2
myeloid dendritic cell antigen processing and presentation	2	85.1×	0.009	HLA-DRA, HLA-DRB1
forebrain astrocyte development	2	85.1×	0.009	KRAS, NF1
positive regulation of membrane tubulation	2	85.1×	0.009	ATP10A, ASAP1
MAPK cascade	6	7.0×	0.011	BRAF, ZFP36L1, FGFR3, KRAS, NF1, NRAS
T cell differentiation in thymus	4	12.5×	0.013	BRAF, ZFP36L1, TP53, B2M
negative regulation of Rac protein signal transduction	2	63.8×	0.015	ARHGAP24, NF1
regulation of T-helper cell differentiation	2	63.8×	0.015	HLA-DRA, HLA-DRB1

Therapeutics

Drugs indicated for this disease

12 approved, 32 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Aldesleukin	Approved (phase 4)
Binimetinib	Approved (phase 4)
Dacarbazine	Approved (phase 4)
Encorafenib	Approved (phase 4)
INTERFERON ALFA-2B	Approved (phase 4)
Ipilimumab	Approved (phase 4)
Lifileucel	Approved (phase 4)
Nivolumab	Approved (phase 4)
PEGINTERFERON ALFA-2B	Approved (phase 4)
Pembrolizumab	Approved (phase 4)
Talimogene Laherparepvec	Approved (phase 4)
Vemurafenib	Approved (phase 4)
Aflibercept	Phase 3 (in late-stage trials)
Atezolizumab	Phase 3 (in late-stage trials)
Bempegaldesleukin	Phase 3 (in late-stage trials)
Carboplatin	Phase 3 (in late-stage trials)
Cisplatin	Phase 3 (in late-stage trials)
Cobimetinib	Phase 3 (in late-stage trials)
Dabrafenib	Phase 3 (in late-stage trials)
Epacadostat	Phase 3 (in late-stage trials)
Ergocalciferol	Phase 3 (in late-stage trials)
Filgrastim	Phase 3 (in late-stage trials)
Fludarabine	Phase 3 (in late-stage trials)
Fotemustine	Phase 3 (in late-stage trials)
GP-100 ANTIGEN	Phase 3 (in late-stage trials)
INTERFERON GAMMA-1B	Phase 3 (in late-stage trials)
Incomplete Freund’S Adjuvant	Phase 3 (in late-stage trials)
Interferon Alfa	Phase 3 (in late-stage trials)
Melphalan	Phase 3 (in late-stage trials)
Oblimersen Sodium	Phase 3 (in late-stage trials)
Paclitaxel	Phase 3 (in late-stage trials)
QS-21	Phase 3 (in late-stage trials)
Regramostim	Phase 3 (in late-stage trials)
Relatlimab	Phase 3 (in late-stage trials)
Rose Bengal Free Acid	Phase 3 (in late-stage trials)
Sargramostim	Phase 3 (in late-stage trials)
Sodium Chloride	Phase 3 (in late-stage trials)
Spartalizumab	Phase 3 (in late-stage trials)
Temozolomide	Phase 3 (in late-stage trials)
Toripalimab	Phase 3 (in late-stage trials)
Trametinib	Phase 3 (in late-stage trials)
Tremelimumab	Phase 3 (in late-stage trials)
Tyrosinase	Phase 3 (in late-stage trials)
Vinblastine	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): 6-O-BENZYLGUANINE, Abemaciclib, Acetaminophen, Acetylcysteine, Alvocidib, Aspirin, Astuprotimut-R, Atorvastatin, Azacitidine, Bcg Vaccine, Bevacizumab, Cabozantinib, Capmatinib, Carmustine, Ceritinib, Cyclosporine, Dasatinib Anhydrous, Denileukin Diftitox, Denosumab, Endostatin, N-Terminal-Mggshhhhh, Entrectinib, Everolimus, Fenretinide, Fludarabine Phosphate, Hyaluronidase, Ibrutinib, Imiquimod, Indomethacin, Irofulven, Lomustine, MUROMONAB-CD3, Molgramostim, Mycophenolate Mofetil, Nilotinib, Pegargiminase, Pelareorep, Pentamidine, Perifosine, Polidocanol, Ramucirumab, Regorafenib, Riluzole, Rituximab, Rubitecan, Selumetinib, Semaxanib, Sulindac, Tanespimycin, Temsirolimus, Thalidomide, Tretinoin, Vatalanib, Vinorelbine.

Drug target analysis

Approved (phase 4): 21 · Phase ≥3: 21 · Phased (≥1): 24 · Undrugged: 51

Druggability breadth: 70 of 159 evidence-associated genes (44%) 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
TERT	BERBERINE
CCND1	PALBOCICLIB
BRAF	VEMURAFENIB
CDK4	PALBOCICLIB
SLTM	CABOZANTINIB
EZH2	TAZEMETOSTAT
FGFR3	PONATINIB
ALK	CERITINIB
JAK1	FEDRATINIB
JAK2	FEDRATINIB
KRAS	VEMURAFENIB
SLK	AFATINIB
TP53	NITROFURANTOIN
TYR	ASCORBIC ACID
UGT1A10	DICLOFENAC
UGT1A6	DICLOFENAC
UGT1A7	DICLOFENAC
UGT1A9	DICLOFENAC
HDAC4	CELECOXIB
CASP8	PRIMAQUINE PHOSPHATE
TUBB3	COLCHICINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TP53	196	4
JAK2	100	4
SLK	81	4
JAK1	68	4
FGFR3	64	4
ALK	61	4
CDK4	56	4
BRAF	48	4
CCND1	35	4
HDAC4	31	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
PALBOCICLIB	4	ALK, CCND1, CDK4
ABEMACICLIB	4	BRAF, CCND1, CDK4
RIBOCICLIB	4	CCND1, CDK4
TRILACICLIB	4	CCND1, CDK4
VEMURAFENIB	4	BRAF, KRAS
PONATINIB	4	BRAF, FGFR3, JAK1, JAK2
FEDRATINIB	4	ALK, BRAF, CDK4, FGFR3, JAK1, JAK2
SORAFENIB	4	BRAF, FGFR3, SLK
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	ALK, BRAF, JAK1, JAK2
INFIGRATINIB PHOSPHATE	4	ALK, BRAF, FGFR3, JAK2
INFIGRATINIB	4	ALK, BRAF, FGFR3, JAK2
REGORAFENIB	4	BRAF
DABRAFENIB	4	BRAF, CDK4, JAK2, KRAS
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF
ENCORAFENIB	4	BRAF, CDK4
TOVORAFENIB	4	BRAF
PAZOPANIB	4	ALK, BRAF, FGFR3, JAK2, SLK
DASATINIB	4	BRAF, FGFR3, JAK2, SLK
ERLOTINIB	4	ALK, BRAF, JAK2, SLK
GEFITINIB	4	BRAF, SLK
IMATINIB	4	BRAF
CERITINIB	4	ALK, CDK4, FGFR3, JAK1, JAK2
GILTERITINIB	4	ALK, CDK4, SLK
NINTEDANIB	4	ALK, CDK4, FGFR3, JAK1, JAK2, SLK
SUNITINIB	4	ALK, CDK4, FGFR3, JAK1, JAK2, SLK
CABOZANTINIB	4	SLTM

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 23.

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

Symbol	Assays	Type breakdown
JAK2	2,018	Binding:1911, Functional:51, ADMET:48, Unclassified:4, Toxicity:4
HDAC4	1,941	Binding:1919, ADMET:13, Functional:6, Toxicity:3
ALK	1,815	Binding:1801, Functional:13, ADMET:1
TUBB3	1,781	Binding:1741, Functional:34, ADMET:6
JAK1	1,502	Binding:1428, Functional:49, ADMET:24, Toxicity:1
BRAF	1,442	Binding:1400, Functional:37, ADMET:5
CDK4	1,142	Binding:1086, Functional:53, ADMET:2, Toxicity:1
FGFR3	975	Binding:948, Functional:18, ADMET:9
TP53	869	Binding:775, ADMET:83, Functional:10, Toxicity:1
KRAS	861	Binding:829, Functional:32
EZH2	839	Binding:833, Functional:6
CCND1	576	Binding:574, Functional:1, ADMET:1
TERT	391	Binding:389, Functional:2
SLK	280	Binding:279, Functional:1
TYR	211	Binding:209, ADMET:2
UGT1A9	153	ADMET:149, Binding:4
CASP8	116	Binding:106, Functional:10
UGT1A10	101	ADMET:99, Binding:2
UGT1A8	87	ADMET:86, Binding:1
UGT1A6	76	ADMET:71, Binding:5
UGT1A7	76	ADMET:74, Binding:2
SETDB1	65	Binding:64, ADMET:1
CDK10	59	Binding:59
GNAQ	27	Binding:27
NRAS	18	Binding:18
CDH1	18	Binding:18
RNASE1	17	Binding:16, ADMET:1
SLTM	14	Binding:14
HSD17B12	12	Binding:12
PTEN	8	Binding:8
B2M	5	Binding:5
TYRP1	3	Binding:3
BACH2	3	Binding:3
CDKN2A	2	Binding:2
MCF2L	2	Binding:2
MYNN	2	Binding:2
SLC24A4	1	Functional:1
POT1	1	Binding:1
XPO4	1	Binding:1
CDKAL1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RNASE1	4.6.1.18	pancreatic ribonuclease
BRAF	2.7.10.2, 2.7.11.1	non-specific protein-tyrosine kinase, non-specific serine/threonine protein kinase
CDK4	2.7.11.22	cyclin-dependent kinase
EZH2	2.1.1.356	[histone H3]-lysine27 N-trimethyltransferase
FGFR3	2.7.10.1	receptor protein-tyrosine kinase
ALK	2.7.10.1	receptor protein-tyrosine kinase
JAK1	2.7.10.2	non-specific protein-tyrosine kinase
JAK2	2.7.10.2	non-specific protein-tyrosine kinase
KRAS	3.6.5.2	small monomeric GTPase
PTEN	3.1.3.16, 3.1.3.67	protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase
SETDB1	2.1.1.355, 2.1.1.366, 2.1.1.368	[histone H3]-lysine9 N-trimethyltransferase, [histone H3]-N6,N6-dimethyl-lysine9 N-methyltransferase, [histone H3]-lysine9 N-dimethyltransferase
TYR	1.14.18.1	tyrosinase
UGT1A10	2.4.1.17	glucuronosyltransferase
UGT1A6	2.4.1.17	glucuronosyltransferase
UGT1A7	2.4.1.17	glucuronosyltransferase
UGT1A8	2.4.1.17	glucuronosyltransferase
UGT1A9	2.4.1.17	glucuronosyltransferase
ATP10A	7.6.2.1	P-type phospholipid transporter
ATP11A	7.6.2.1	P-type phospholipid transporter
HDAC4	3.5.1.98	histone deacetylase
CASP8	3.4.22.61	caspase-8
CDK10	2.7.11.22	cyclin-dependent kinase
HSD17B12	1.1.1.62	17beta-estradiol 17-dehydrogenase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
TERT	391
CCND1	576
BRAF	1,442
CDK4	1,142
EZH2	839
FGFR3	975
ALK	1,815
JAK1	1,502
JAK2	2,018
KRAS	861
SLK	280
TP53	869
TYR	211
UGT1A10	101
UGT1A9	153
HDAC4	1,941
CASP8	116
TUBB3	1,781

Pharmacogenomics

Cohort genes with a PharmGKB record: 74; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

25 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)
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
PALBOCICLIB	4	ALK, CCND1, CDK4
ABEMACICLIB	4	BRAF, CCND1, CDK4
RIBOCICLIB	4	CCND1, CDK4
TRILACICLIB	4	CCND1, CDK4
VEMURAFENIB	4	BRAF, KRAS
PONATINIB	4	BRAF, FGFR3, JAK1, JAK2
FEDRATINIB	4	ALK, BRAF, CDK4, FGFR3, JAK1, JAK2
DASATINIB ANHYDROUS	4	BRAF
RUXOLITINIB	4	ALK, BRAF, JAK1, JAK2
INFIGRATINIB PHOSPHATE	4	ALK, BRAF, FGFR3, JAK2
INFIGRATINIB	4	ALK, BRAF, FGFR3, JAK2
COBIMETINIB	4	BRAF
NILOTINIB	4	BRAF
TOVORAFENIB	4	BRAF
PAZOPANIB	4	ALK, BRAF, FGFR3, JAK2, SLK
DASATINIB	4	BRAF, FGFR3, JAK2, SLK
ERLOTINIB	4	ALK, BRAF, JAK2, SLK
GEFITINIB	4	BRAF, SLK
IMATINIB	4	BRAF
GILTERITINIB	4	ALK, CDK4, SLK
NINTEDANIB	4	ALK, CDK4, FGFR3, JAK1, JAK2, SLK
SUNITINIB	4	ALK, CDK4, FGFR3, JAK1, JAK2, SLK
CABOZANTINIB	4	SLTM

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	21	TERT, CCND1, BRAF, CDK4, SLTM, EZH2, FGFR3, ALK, JAK1, JAK2 (+11 more)
B	Phased (≥1) drug, not yet approved	3	NRAS, CDK10, HSD17B12
C	Druggable family + PDB, no drug	6	RNASE1, HLA-DRA, B2M, PTEN, SETDB1, TPCN2
D	Druggable family + AlphaFold only, no drug	2	SLC45A2, UGT1A8
E	Difficult family or no structure, no drug	43	RNASE3, CDKN2A, GNAQ, NF1, SLC24A4, ZFP36L1, TAL2, TERC, TFAP2B, TYRP1 (+33 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SLC45A2	0	TYR
CDKN2A	2	CDK4
NF1	0	KRAS, BRAF, NRAS
PTEN	8	TP53
CDKN2B	0	CDK4, TP53
RNASE1	17	—
RNASE3	0	—
GNAQ	27	—
HLA-DRA	0	—
B2M	5	—
SETDB1	65	—
SLC24A4	1	—
ZFP36L1	0	—
TAL2	0	—
TERC	0	—
TFAP2B	0	—
TYRP1	3	—
UGT1A8	87	—
KIAA0930	0	—
ATP10A	0	—
ATP11A	0	—
BACH2	3	—
MCF2L	2	—
DNAJB4	0	—
MYNN	2	—
PIGU	0	—
RTEL1	0	—
RALY	0	—
FHIP2B	0	—
RAPGEF5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 188.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	53
Not specified	47
PHASE1	46
PHASE1/PHASE2	25
PHASE3	8
EARLY_PHASE1	6
PHASE2/PHASE3	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01274338	PHASE3	ACTIVE_NOT_RECRUITING	Ipilimumab or High-Dose Interferon Alfa-2b in Treating Patients With High-Risk Stage III-IV Melanoma That Has Been Removed by Surgery
NCT02339571	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	A Phase II/III Trial of Nivolumab, Ipilimumab, and GM-CSF in Patients With Advanced Melanoma
NCT02506153	PHASE3	ACTIVE_NOT_RECRUITING	Physician/Patient Choice of Either High-Dose Recombinant Interferon Alfa-2B or Ipilimumab, Versus Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery
NCT06624644	PHASE2/PHASE3	RECRUITING	A Trial of LNS8801 With or Without Pembrolizumab in Patients With Refractory Melanoma
NCT07068074	PHASE3	NOT_YET_RECRUITING	A Randomized Phase III Study of Management of Treatment Naive Primary Melanoma in Elderly Patients
NCT00019682	PHASE3	COMPLETED	Aldesleukin With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Melanoma
NCT00110019	PHASE3	COMPLETED	Carboplatin and Paclitaxel With or Without Sorafenib Tosylate in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
NCT01729663	PHASE2/PHASE3	UNKNOWN	Phase II/III Clinical Study CSF470 Plus BCG Plus GM-CSF vs IFN Alpha 2b in Stage IIB, IIC and III Melanoma Patients
NCT01989572	PHASE3	COMPLETED	Sargramostim, Vaccine Therapy, or Sargramostim and Vaccine Therapy in Preventing Disease Recurrence in Patients With Melanoma That Has Been Removed By Surgery
NCT02288897	PHASE3	TERMINATED	PV-10 vs Chemotherapy or Oncolytic Viral Therapy for Treatment of Locally Advanced Cutaneous Melanoma
NCT06320353	PHASE3	UNKNOWN	Study сomparing the Efficacy and Safety of RPH-075 and Keytruda® in Patients With Unresectable or Metastatic Skin Melanoma
NCT01134614	PHASE2	ACTIVE_NOT_RECRUITING	Ipilimumab With or Without Sargramostim in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed by Surgery
NCT01708941	PHASE2	ACTIVE_NOT_RECRUITING	Ipilimumab With or Without High-Dose Recombinant Interferon Alfa-2b in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery
NCT02196181	PHASE2	ACTIVE_NOT_RECRUITING	Testing Two Different Treatment Schedules of Dabrafenib and Trametinib for Skin Cancer Which Has Spread
NCT02231775	PHASE2	ACTIVE_NOT_RECRUITING	Dabrafenib and Trametinib Before and After Surgery in Treating Patients With Stage IIIB-C Melanoma With BRAF V600 Mutation
NCT02581930	PHASE2	ACTIVE_NOT_RECRUITING	Ibrutinib in Treating Patients With Refractory Metastatic Cutaneous Melanoma
NCT02910700	PHASE2	ACTIVE_NOT_RECRUITING	Nivolumab With Trametinib and Dabrafenib, or Encorafenib and Binimetinib in Treating Patients With BRAF Mutated Metastatic or Unresectable Stage III-IV Melanoma
NCT02965716	PHASE2	ACTIVE_NOT_RECRUITING	Talimogene Laherparepvec and Pembrolizumab in Treating Patients With Stage III-IV Melanoma
NCT03611868	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study of APG-115 in as a Monotherapy or Combination With Pembrolizumab in Patients With Metastatic Melanomas or Advanced Solid Tumors
NCT03719131	PHASE2	ACTIVE_NOT_RECRUITING	Rituximab and Hyaluronidase Human in Patients With Advanced Melanoma Undergoing Nivolumab and Ipilimumab Therapy
NCT03767348	PHASE2	ACTIVE_NOT_RECRUITING	Study of RP1 Monotherapy and RP1 in Combination With Nivolumab (IGNYTE)
NCT03842943	PHASE2	RECRUITING	Neoadjuvant Combination Immunotherapy for Stage III Melanoma
NCT03947385	PHASE1/PHASE2	RECRUITING	Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
NCT04511013	PHASE2	RECRUITING	A Study to Compare the Administration of Encorafenib + Binimetinib + Nivolumab Versus Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases
NCT04708418	PHASE2	ACTIVE_NOT_RECRUITING	A Study Evaluating Whether Pembrolizumab Alone or in Combination With CMP-001 Improves Efficacy of Treatment in Patients With Operable Melanoma
NCT05086692	PHASE1/PHASE2	RECRUITING	A Beta-only IL-2 ImmunoTherapY Study
NCT05267626	PHASE1/PHASE2	RECRUITING	Study of AU-007, A Monoclonal Antibody That Binds to IL-2 and Inhibits IL-2Rα Binding, in Patients With Unresectable Locally Advanced or Metastatic Cancer
NCT05669430	PHASE1/PHASE2	RECRUITING	A Study of GV20-0251 Monotherapy and GV20-0251 in Combination With Pembrolizumab in Participants With Solid Tumor Malignancies
NCT05824975	PHASE1/PHASE2	RECRUITING	A Study to Evaluate the Safety and Therapeutic Activity of GI-102 As a Single Agent and in Combination with Conventional Anti-cancer Drugs, Pembrolizumab or Trastuzumab Deruxtecan(T-DXd) in Patients with Advanced Solid Tumors (KEYNOTE-G08)
NCT05970497	PHASE1/PHASE2	RECRUITING	A Study Assessing KB707 for the Treatment of Locally Advanced or Metastatic Solid Tumors
NCT06090266	PHASE1/PHASE2	RECRUITING	A Study of OR502, a Monoclonal Antibody Targeting LILRB2, Alone and in Combination With Anticancer Agents
NCT06194929	PHASE1/PHASE2	RECRUITING	Defactinib and Avutometinib, With or Without Encorafenib, for the Treatment of Patients With Brain Metastases From Cutaneous Melanoma
NCT06223659	PHASE2	RECRUITING	EMLA Topical Cream for Treatment of Pain in Patients Receiving Intra-Dermal Technetium 99 Injections for Lymphoscintigraphy for Skin Cancers
NCT06265285	PHASE2	RECRUITING	Comparison of In-Home Versus In-Clinic Administration of Subcutaneous Nivolumab Through Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) Program
NCT06319196	PHASE2	RECRUITING	Clear Me: Interception Trial to Detect and Clear Molecular Residual Disease in Patients With High-risk Melanoma
NCT06784648	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Different Doses of BI-1607 in Combination With Pembrolizumab and Ipilimumab, in Participants With Unresectable or Metastatic Melanoma
NCT06965231	PHASE2	RECRUITING	Perioperative Toripalimab and Endostatin for Stage II Melanoma: A Phase II Trial
NCT06984328	PHASE2	ACTIVE_NOT_RECRUITING	Study of the Effectiveness and Safety of Acasunlimab Alone and With Pembrolizumab to Treat Advanced Melanoma of the Skin That Has Returned After Treatment With an Approved Checkpoint Inhibitor Therapy (ABBIL1TY MELANOMA-07)
NCT06999980	PHASE2	RECRUITING	Neo IRENIE (NEOadjuvant Ipilimumab, RElatlimab, NIvolumab Evaluation)
NCT07130032	PHASE2	RECRUITING	Efficacy And Safety Of Anti-PD-1/PD-L1 Antibodies In Combination With Bevacizumab And Metronomic Cyclophosphamide In Patients With Non-Small Cell Lung Cancer And Cutaneous Melanoma Previously Treated With Immune Checkpoint Blockade

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ALDESLEUKIN	4	13
DABRAFENIB	4	8
TRAMETINIB	4	6
BINIMETINIB	4	5
ENCORAFENIB	4	5
SORAFENIB	4	4
IPILIMUMAB	4	3
FLUORESCEIN	4	2
LIFILEUCEL	4	2
SARGRAMOSTIM	4	2
TALIMOGENE LAHERPAREPVEC	4	2
CAPMATINIB	4	1
CEMIPLIMAB	4	1
CERITINIB	4	1
CRIZOTINIB	4	1
DACARBAZINE	4	1
ENTRECTINIB	4	1
ERIBULIN	4	1
NIVOLUMAB	4	1
PEGFILGRASTIM	4	1
PEMBROLIZUMAB	4	1
REGORAFENIB	4	1
RELATLIMAB	4	1
RILUZOLE	4	1
ROMIDEPSIN	4	1
SELUMETINIB	4	1
TEMSIROLIMUS	4	1
VINBLASTINE SULFATE	4	1
ABEXINOSTAT	3	1
AVUTOMETINIB	3	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 58 predictive associations from 63 curated evidence items; also 2 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
BRAF V600E	Vemurafenib	Sensitivity/Response	CIViC A	EID1409 +1
BRAF V600	Dabrafenib + Trametinib	Sensitivity/Response	CIViC A	EID1411
NRAS Mutation	Binimetinib	Sensitivity/Response	CIViC B	EID1472 +1
BRAF K601E	Dabrafenib	Sensitivity/Response	CIViC B	EID2812
BRAF V600E	Dabrafenib	Sensitivity/Response	CIViC B	EID2146
BRAF V600E	Dabrafenib + Trametinib	Sensitivity/Response	CIViC B	EID3758
BRAF V600K	Trametinib + Dabrafenib	Sensitivity/Response	CIViC B	EID4181
CCND1 Amplification	Sorafenib + Carboplatin + Paclitaxel	Sensitivity/Response	CIViC B	EID1495
HLA-DRA EXPRESSION	Nivolumab + Atezolizumab + Pembrolizumab	Sensitivity/Response	CIViC B	EID985
KRAS Amplification	Sorafenib + Docetaxel + Carboplatin	Sensitivity/Response	CIViC B	EID1497
NRAS Mutation	Docetaxel + Trametinib	Sensitivity/Response	CIViC B	EID1225
NRAS Mutation	Ribociclib + Binimetinib	Sensitivity/Response	CIViC B	EID2931
NRAS Q61	Binimetinib	Sensitivity/Response	CIViC B	EID1226
RAF1 Amplification	Paclitaxel + Sorafenib + Carboplatin	Sensitivity/Response	CIViC B	EID1496
MET Overexpression	Vemurafenib	Resistance	CIViC B	EID1581 +1
BRAF V600R	Dabrafenib + Vemurafenib	Resistance	CIViC B	EID8948
ALK Alternative Transcript (ATI)	Crizotinib	Sensitivity/Response	CIViC C	EID1936
BRAF L597Q	Trametinib	Sensitivity/Response	CIViC C	EID4905
BRAF L597S	MEK Inhibitor REC-4881	Sensitivity/Response	CIViC C	EID1460
BRAF L597V	Trametinib	Sensitivity/Response	CIViC C	EID1463
BRAF V600R	Vemurafenib	Sensitivity/Response	CIViC C	EID4172
BRAF V600_K601DELINSD	Vemurafenib	Sensitivity/Response	CIViC C	EID4789
KIAA1549::BRAF Fusion	Trametinib	Sensitivity/Response	CIViC C	EID1571
NRAS Q61	Selumetinib	Sensitivity/Response	CIViC C	EID1473
PPFIBP2::BRAF Fusion	Trametinib	Sensitivity/Response	CIViC C	EID1570
NF1 Mutation	Vemurafenib	Resistance	CIViC C	EID1470 +1
B2M S14FS	Pembrolizumab	Resistance	CIViC C	EID1569
GNAQ Q209P	Vemurafenib	Resistance	CIViC C	EID1533
JAK1 Q503*	Pembrolizumab	Resistance	CIViC C	EID1567
JAK2 c.1641+1dup	Pembrolizumab	Resistance	CIViC C	EID1568

+28 more predictive associations (showing top 30 by evidence level).