Uveal melanoma

Summary

Uveal melanoma (MONDO:0006486) is a cancer (an umbrella term covering 8 Mondo subtypes) with 15 cohort genes (46 GWAS associations across 8 studies; 8 CIViC-evidence somatic drivers; 4 ClinVar predisposition records) and 194 clinical trials. The dominant Reactome pathway is PLC beta mediated events (3 cohort genes). Molecularly, GNA11 Mutation confers sensitivity to Cabozantinib in Uveal Melanoma (CIViC Level B); 17 further subtype–drug associations are mapped below. Top therapeutic interventions include tebentafusp, ipilimumab, and dacarbazine.

At a glance

• Classification: Cancer
• Prevalence: 1-9 / 100 000 (Europe) [Orphanet-validated]
• Umbrella term: 8 Mondo subtypes
• Cohort genes: 15
• GWAS associations: 46
• ClinVar variants: 4
• Phenotypes (HPO): 17
• Clinical trials: 194
• Precision-medicine evidence (CIViC): 18 subtype–drug associations

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Annual incidence	1-9 / 1 000 000	0.5	Europe	Validated
Lifetime Prevalence	1-9 / 100 000	6	Europe	Validated
Point prevalence	1-9 / 100 000		Europe	Validated
Annual incidence	<1 / 1 000 000	0.03	Africa	Not yet validated

Signs & symptoms

Clinical features (HPO)

17 HPO clinical features (Orphanet curated; top 17 by frequency):

HPO ID	Term	Frequency
HP:0000572	Visual loss	Very frequent (80-99%)
HP:0001098	Abnormal fundus morphology	Very frequent (80-99%)
HP:0012054	Choroidal melanoma	Very frequent (80-99%)
HP:0000541	Retinal detachment	Frequent (30-79%)
HP:0011524	Iris melanoma	Frequent (30-79%)
HP:0012055	Ciliary body melanoma	Frequent (30-79%)
HP:0000539	Abnormality of refraction	Occasional (5-29%)
HP:0007902	Vitreous hemorrhage	Occasional (5-29%)
HP:0007906	Ocular hypertension	Occasional (5-29%)
HP:0008494	Inferior lens subluxation	Occasional (5-29%)
HP:0010920	Zonular cataract	Occasional (5-29%)
HP:0011499	Mydriasis	Occasional (5-29%)
HP:0012508	Metamorphopsia	Occasional (5-29%)
HP:0030786	Photopsia	Occasional (5-29%)
HP:0030800	Abnormal visual accommodation	Occasional (5-29%)
HP:0100533	Inflammatory abnormality of the eye	Very rare (<1-4%)
HP:0200026	Ocular pain	Very rare (<1-4%)

Identifiers

Disease identifiers

Field	Value
Canonical name	uveal melanoma
Mondo ID	MONDO:0006486
EFO	EFO:1000616
MeSH	C536494
OMIM	155720
Orphanet	39044
DOID	DOID:6039
NCIT	C7712
UMLS	C0220633
MedGen	65077
GARD	0008621
MedDRA	10061252
Anatomy (UBERON)	UBERON:0001768
Is cancer (heuristic)	yes

Also known as: intraocular melanoma · iris melanoma · melanoma (disease) of uvea · melanoma of the uvea · melanoma of uvea · melanoma, uveal, malignant · uvea melanoma · uvea melanoma (disease) · uveal melanoma

Data availability: 4 ClinVar variants · 46 GWAS associations (8 studies) · 100 cell lines · 10 intOGen driver records.

Disease family

An umbrella term covering 8 Mondo subtypes.

Classification path: human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › nervous system cancer › sensory system cancer › ocular cancer › uveal cancer › uveal melanoma

Related subtypes (2): iris cancer, choroid cancer

Subtypes (8): spindle cell intraocular melanoma, malignant choroid melanoma, mixed cell uveal melanoma, posterior uveal melanoma, intermediate cell type uveal melanoma, iris melanoma, necrotic uveal melanoma, epithelioid cell uveal melanoma

Genetics & variants

GWAS landscape

46 GWAS associations across 8 studies. Top hits map to 22 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs12203592	7e-19	IRF4	T
rs12913832	3e-15	HERC2	A
rs1129038	6e-12	HERC2	C	0.56
chr13:21440496	2e-11		A
rs3759710	7e-11	TDP1	C	2.16
rs421284	8e-11	CLPTM1L	T
rs11707457	9e-11	LSM3 - LINC01267	T
rs551143	2e-10	RREB1	A
rs452932	2e-09	CLPTM1L	C	1.72
chr3:49771990	7e-09		A
rs370348	1e-08	CLPTM1L	G	1.59
rs2242330	3e-07	STAP1	G	1.67
rs138663667	4e-07	CACNA2D1	T	2.04
rs11074306	5e-07	OCA2	A	1.85
rs13013614	5e-07	LRP1B	A	1.36
rs10758299	5e-07	RFX3-DT	C	2.16
rs9307941	1e-06	FTH1P21 - LINC02272	T	1.52
rs2488636	1e-06	RPS3AP5 - LINC01519	G	1.52
rs12163644	2e-06	LSM3 - LINC01267	A	1.45
rs35257692	2e-06	RN7SL554P - RREB1	G	1.39
rs11692707	2e-06	ARL6IP6 - UBQLN4P2	A	2.05
rs67490716	2e-06	KCNJ3	C	1.49
rs10818329	2e-06	BRINP1 - LINC01613	G	1.49
rs950718	2e-06	SGPL1 - UNC5B	C	1.74
rs285902	2e-06	LINC01957 - TRIM36	A	0.65
rs8038456	4e-06	GNB5	G	1.37
rs117789363	4e-06	AP2B1	C	1.83
rs71308905	4e-06	LINC01991 - LPP-AS2	T	1.74
rs4743170	4e-06	CORO2A	G	1.47
rs17184817	5e-06	DSEL-AS1	G	2.52

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90568461	Mies G	2025	2,426	351,961	Meta-analysis of uveal melanoma genome-wide association studies identifies novel risk loci and population effect size heterogeneity.
GCST90094626	Mobuchon L	2021	1,142	0	Different Pigmentation Risk Loci for High-Risk Monosomy 3 and Low-Risk Disomy 3 Uveal Melanomas.
GCST009071	Thomsen H	2019	590	5,199	Genome-wide study on uveal melanoma patients finds association to DNA repair gene TDP1.
GCST009079	Thomsen H	2019	417	5,199	Genome-wide study on uveal melanoma patients finds association to DNA repair gene TDP1.
GCST009074	Thomsen H	2019	330	5,199	Genome-wide study on uveal melanoma patients finds association to DNA repair gene TDP1.
GCST004661	Mobuchon L	2017	259	0	A GWAS in uveal melanoma identifies risk polymorphisms in the CLPTM1L locus.
GCST009073	Thomsen H	2019	255	5,199	Genome-wide study on uveal melanoma patients finds association to DNA repair gene TDP1.
GCST009077	Thomsen H	2019	253	5,199	Genome-wide study on uveal melanoma patients finds association to DNA repair gene TDP1.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	1
Tier 3: regulatory	3
Tier 4: intronic/intergenic	38

MAF distribution

Bucket	Variants
common (>=0.05)	40
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	26
intergenic_variant	10
regulatory_region_variant	3
unknown	2
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs12203592	6	396321	C>G,T	0.05	intron_variant	IRF4	7e-19	Tier 4: intronic/intergenic
rs12913832	15	28120472	A>C,G	0.05	intron_variant	HERC2	3e-15	Tier 4: intronic/intergenic
rs1129038	15	28111713	C>A,G,T	0.05	3_prime_UTR_variant	HERC2	6e-12	Tier 2: splice/UTR
chr13:21440496							2e-11	Tier 4: intronic/intergenic
rs3759710	14	89955214	G>C	0.05	regulatory_region_variant	TDP1	7e-11	Tier 3: regulatory
rs421284	5	1325475	T>C,G	0.05	intron_variant	CLPTM1L	8e-11	Tier 4: intronic/intergenic
rs11707457	3	14346019	C>T	0.05	regulatory_region_variant	LSM3 - LINC01267	9e-11	Tier 3: regulatory
rs551143	6	7136539	A>C,G	0.05	intron_variant	RREB1	2e-10	Tier 4: intronic/intergenic
rs452932	5	1330138	T>C	0.4	intron_variant	CLPTM1L	2e-09	Tier 4: intronic/intergenic
chr3:49771990							7e-09	Tier 4: intronic/intergenic
rs370348	5	1331104	A>C,G	0.05	intron_variant	CLPTM1L	1e-08	Tier 4: intronic/intergenic
rs2242330	4	67581531	A>C,G,T	0.21	intron_variant	STAP1	3e-07	Tier 4: intronic/intergenic
rs138663667	7	82276774	G>T	0.07	intron_variant	CACNA2D1	4e-07	Tier 4: intronic/intergenic
rs11074306	15	27799396	G>A	0.49	intron_variant	OCA2	5e-07	Tier 4: intronic/intergenic
rs13013614	2	140964558	A>G,T	0.34	intron_variant	LRP1B	5e-07	Tier 4: intronic/intergenic
rs10758299	9	3526656	A>C,T	0.05	intron_variant	RFX3-DT	5e-07	Tier 4: intronic/intergenic
rs9307941	4	156195774	A>C,G,T	0.2	intergenic_variant	FTH1P21 - LINC02272	1e-06	Tier 4: intronic/intergenic
rs2488636	10	84598750	G>A,C	0.05	intergenic_variant	RPS3AP5 - LINC01519	1e-06	Tier 4: intronic/intergenic
rs12163644	3	14343616	G>A	0.13	intergenic_variant	LSM3 - LINC01267	2e-06	Tier 4: intronic/intergenic
rs35257692	6	7080590	T>G	0.34	intron_variant	RN7SL554P - RREB1	2e-06	Tier 4: intronic/intergenic
rs11692707	2	152792976	A>C,G	0.19	intergenic_variant	ARL6IP6 - UBQLN4P2	2e-06	Tier 4: intronic/intergenic
rs67490716	2	154710128	T>C	0.29	intron_variant	KCNJ3	2e-06	Tier 4: intronic/intergenic
rs10818329	9	119517934	G>A,C	0.29	intron_variant	BRINP1 - LINC01613	2e-06	Tier 4: intronic/intergenic
rs950718	10	71094469	A>C,T	0.07	intergenic_variant	SGPL1 - UNC5B	2e-06	Tier 4: intronic/intergenic
rs285902	5	114696728	A>G,T	0.05	intergenic_variant	LINC01957 - TRIM36	2e-06	Tier 4: intronic/intergenic
rs8038456	15	52175349	C>A,G	0.34	intron_variant	GNB5	4e-06	Tier 4: intronic/intergenic
rs117789363	17	35594319	T>C	0.05	intron_variant	AP2B1	4e-06	Tier 4: intronic/intergenic
rs71308905	3	188062069	A>T	0.06	intron_variant	LINC01991 - LPP-AS2	4e-06	Tier 4: intronic/intergenic
rs4743170	9	98138500	A>C,G,T	0.05	intron_variant	CORO2A	4e-06	Tier 4: intronic/intergenic
rs17184817	18	67827215	T>G	0.05	intron_variant	DSEL-AS1	5e-06	Tier 4: intronic/intergenic

ClinVar germline variants

4 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 conflicting classifications of pathogenicity, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
633598	NM_004656.4(BAP1):c.932-8_960del	BAP1	Pathogenic	criteria provided, single submitter
633597	NM_001377142.1(PLCB4):c.1924G>T (p.Asp642Tyr)	PLCB4	Pathogenic	criteria provided, single submitter
1698872	NM_004656.4(BAP1):c.932-151G>A	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
463853	NM_017849.4(TMEM127):c.562A>G (p.Ile188Val)	TMEM127	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 41 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

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

Gene	HGNC	Evidence routes
TERT	TERT	GWAS, Orphanet

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
RNF2	LoF	BRCA,CCRCC,CESC,CHOL,ESCA,HCC,PANCREAS,PLMESO,PRCC,RCC,SACA,SKCM,STAD,UM	CIViC #70
DDX43			CIViC #13005
SLTM	Act	CCRCC,LGGNOS,LUAD,NSCLC,OS,PRCC,RCC	CIViC #52
EIF1AX	Act	LUNG,PRAD,SKCM,UCEC,UM,WDTC	CIViC #1646
ERBB3	Act	BLCA,BRCA,CESC,CHOL,COADREAD,NBL,PRAD,STAD,UCEC,UCS,UTUC	CIViC #1733
GNA11	Act	MEL,UM	CIViC #2308
GNAQ	Act	HCC,NSCLC,SKCM,UM	CIViC #2317
TERT	Act	PRCC	CIViC #79

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RNF2	Orphanet:528084	Non-specific syndromic intellectual disability
EIF1AX	Orphanet:146	Differentiated thyroid carcinoma
ERBB3	Orphanet:137776	Lethal congenital contracture syndrome type 2
ERBB3	Orphanet:388	Hirschsprung disease
GNA11	Orphanet:101049	Familial hypocalciuric hypercalcemia type 2
GNA11	Orphanet:1556	Cutis marmorata telangiectatica congenita
GNA11	Orphanet:39044	Uveal melanoma
GNA11	Orphanet:428	Autosomal dominant hypocalcemia
GNA11	Orphanet:675359	Anastomosing haemangioma
GNA11	Orphanet:714737	Diffuse capillary malformation with overgrowth
GNA11	Orphanet:79483	Phakomatosis cesioflammea
GNA11	Orphanet:79484	Phakomatosis cesiomarmorata
GNAQ	Orphanet:3205	Sturge-Weber syndrome
GNAQ	Orphanet:39044	Uveal melanoma
GNAQ	Orphanet:624	Familial multiple nevi flammei
GNAQ	Orphanet:675359	Anastomosing haemangioma
GNAQ	Orphanet:79483	Phakomatosis cesioflammea
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
TMEM127	Orphanet:29072	Hereditary pheochromocytoma-paraganglioma
TMEM127	Orphanet:404511	Clear cell papillary renal cell carcinoma
HERC2	Orphanet:329195	Developmental delay with autism spectrum disorder and gait instability
OCA2	Orphanet:177901	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 1
OCA2	Orphanet:177904	Prader-Willi syndrome due to paternal deletion of 15q11q13 type 2
OCA2	Orphanet:79432	Oculocutaneous albinism type 2
OCA2	Orphanet:98754	Prader-Willi syndrome due to maternal uniparental disomy of chromosome 15
OCA2	Orphanet:98794	Angelman syndrome due to maternal 15q11q13 deletion
PLCB4	Orphanet:137888	Auriculocondylar syndrome
BAP1	Orphanet:2495	Meningioma
BAP1	Orphanet:289539	BAP1-related tumor predisposition syndrome
BAP1	Orphanet:39044	Uveal melanoma
BAP1	Orphanet:50251	Pleural mesothelioma
BAP1	Orphanet:528084	Non-specific syndromic intellectual disability
BAP1	Orphanet:618	Familial melanoma

Cohort genes → proteins

15 cohort genes, 15 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	4
civic_only	7
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RNF2	HGNC:10061	ENSG00000121481	Q99496	E3 ubiquitin-protein ligase RING2	civic_evidence
DDX43	HGNC:18677	ENSG00000080007	Q9NXZ2	Probable ATP-dependent RNA helicase DDX43	civic_evidence
SLTM	HGNC:20709	ENSG00000137776	Q9NWH9	SAFB-like transcription modulator	civic_evidence
EIF1AX	HGNC:3250	ENSG00000173674	P47813	Eukaryotic translation initiation factor 1A, X-chromosomal	civic_evidence
ERBB3	HGNC:3431	ENSG00000065361	P21860	Receptor tyrosine-protein kinase erbB-3	civic_evidence
GNA11	HGNC:4379	ENSG00000088256	P29992	Guanine nucleotide-binding protein subunit alpha-11	civic_evidence
GNAQ	HGNC:4390	ENSG00000156052	P50148	Guanine nucleotide-binding protein G(q) subunit alpha	civic_evidence
TERT	HGNC:11730	ENSG00000164362	O14746	Telomerase reverse transcriptase	gwas
CLPTM1L	HGNC:24308	ENSG00000049656	Q96KA5	Lipid scramblase CLPTM1L	gwas
TMEM127	HGNC:26038	ENSG00000135956	O75204	Transmembrane protein 127	clinvar
HERC2	HGNC:4868	ENSG00000128731	O95714	E3 ubiquitin-protein ligase HERC2	gwas
OCA2	HGNC:8101	ENSG00000104044	Q04671	P protein	gwas
PLCB4	HGNC:9059	ENSG00000101333	Q15147	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4	clinvar
MAGI1	HGNC:946	ENSG00000151276	Q96QZ7	Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1	clinvar
BAP1	HGNC:950	ENSG00000163930	Q92560	Ubiquitin carboxyl-terminal hydrolase BAP1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RNF2	E3 ubiquitin-protein ligase RING2	E3 ubiquitin-protein ligase that mediates monoubiquitination of ‘Lys-119’ of histone H2A (H2AK119Ub), thereby playing a central role in histone code and gene regulation.
SLTM	SAFB-like transcription modulator	When overexpressed, acts as a general inhibitor of transcription that eventually leads to apoptosis.
EIF1AX	Eukaryotic translation initiation factor 1A, X-chromosomal	Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5’-untranslated region, and locates the initiation codon.
ERBB3	Receptor tyrosine-protein kinase erbB-3	Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins.
GNA11	Guanine nucleotide-binding protein subunit alpha-11	Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.
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.
TERT	Telomerase reverse transcriptase	Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes.
CLPTM1L	Lipid scramblase CLPTM1L	Scramblase that mediates the translocation of glucosaminylphosphatidylinositol (alpha-D-GlcN-(1-6)-(1,2-diacyl-sn-glycero-3-phospho)-1D-myo-inositol, GlcN-PI) across the endoplasmic reticulum (ER) membrane, from the cytosolic leaflet to th…
TMEM127	Transmembrane protein 127	Controls cell proliferation acting as a negative regulator of TOR signaling pathway mediated by mTORC1.
HERC2	E3 ubiquitin-protein ligase HERC2	E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes.
OCA2	P protein	Contributes to a melanosome-specific anion (chloride) current that modulates melanosomal pH for optimal tyrosinase activity required for melanogenesis and the melanosome maturation.
PLCB4	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4	Activated phosphatidylinositol-specific phospholipase C enzymes catalyze the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) involved in G-protein coupled receptor signaling pathways.
MAGI1	Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1	Plays a role in coupling actin fibers to cell junctions in endothelial cells, via its interaction with AMOTL2 and CDH5.
BAP1	Ubiquitin carboxyl-terminal hydrolase BAP1	Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A and HCFC1.

Protein-family classification

Druggable: 5 · Difficult: 2 · Unknown: 8 · Druggable fraction: 0.33

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
Ion channel	1	7.4×	0.379
Kinase	2	3.7×	0.379
Protease	1	2.4×	0.680
Transcription factor	2	1.1×	0.729
Other/Unknown	8	1.0×	0.729
Enzyme (other)	1	0.8×	0.729

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RNF2	Transcription factor	no	2.3.2.27	Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_CS
DDX43	Other/Unknown	no		RNA-helicase_DEAD-box_CS, Helicase_C-like, KH_dom
SLTM	Other/Unknown	no		RRM_dom, SAP_dom, Nucleotide-bd_a/b_plait_sf
EIF1AX	Other/Unknown	no		TIF_eIF-1A, RNA-binding_domain_S1_IF1, NA-bd_OB-fold
ERBB3	Kinase	yes	2.7.10.1	Rcpt_L-dom, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom
GNA11	Other/Unknown	no		Gprotein_alpha_Q, Gprotein_alpha_su, GproteinA_insert
GNAQ	Other/Unknown	no		Gprotein_alpha_Q, Gprotein_alpha_su, GproteinA_insert
TERT	Other/Unknown	no		RT_dom, Telomerase_RT, Telomerase_RBD
CLPTM1L	Other/Unknown	no		CLPTM1
TMEM127	Other/Unknown	no		TMEM127, TMEM127_TM
HERC2	Transcription factor	no		Reg_chr_condens, Znf_ZZ, HECT_dom
OCA2	Ion channel	yes		Cit_transptr-like_dom, Diverse_Ion_Transporter
PLCB4	Enzyme (other)	yes	3.1.4.11	C2_dom, PLipase_C_PInositol-sp_X_dom, PI-PLC_fam
MAGI1	Kinase	yes		WW_dom, PDZ, Guanylate_kin-like_dom
BAP1	Protease	yes	3.4.19.12	Peptidase_C12_UCH, Peptidase_C12_UCH_sf, Papain-like_cys_pep_sf

Expression context

Cohort genes with no expression data: 0.

13 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)	15
unknown	0

Top tissues across cohort

Tissue	Cohort genes
sural nerve	4
primordial germ cell in gonad	3
secondary oocyte	2
jejunal mucosa	2
ileal mucosa	2
cortical plate	1
ganglionic eminence	1
oocyte	1
calcaneal tendon	1
tibia	1
endothelial cell	1
skeletal muscle tissue of rectus abdominis	1
dorsal root ganglion	1
trigeminal ganglion	1
pancreatic ductal cell	1
CA1 field of hippocampus	1
dorsal motor nucleus of vagus nerve	1
postcentral gyrus	1
olfactory bulb	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RNF2	178	ubiquitous	marker	primordial germ cell in gonad, cortical plate, ganglionic eminence
DDX43	174	broad	yes	oocyte, secondary oocyte, primordial germ cell in gonad
SLTM	291	ubiquitous	marker	calcaneal tendon, sural nerve, tibia
EIF1AX	295	ubiquitous	marker	endothelial cell, skeletal muscle tissue of rectus abdominis, primordial germ cell in gonad
ERBB3	274	broad	marker	trigeminal ganglion, jejunal mucosa, dorsal root ganglion
GNA11	299	ubiquitous	marker	ileal mucosa, jejunal mucosa, pancreatic ductal cell
GNAQ	302	ubiquitous	marker	CA1 field of hippocampus, dorsal motor nucleus of vagus nerve, postcentral gyrus
TERT	105	broad	yes	stromal cell of endometrium, type B pancreatic cell, olfactory bulb
CLPTM1L	255	ubiquitous	marker	ileal mucosa, kidney epithelium, right lobe of thyroid gland
TMEM127	284	ubiquitous	marker	leukocyte, monocyte, blood
HERC2	146		marker	sural nerve, right hemisphere of cerebellum, cerebellar cortex
OCA2	192	tissue_specific	marker	pigmented layer of retina, choroid plexus epithelium, secondary oocyte
PLCB4	273	ubiquitous	marker	parotid gland, lateral nuclear group of thalamus, sural nerve
MAGI1	133	ubiquitous	marker	ventricular zone, sural nerve, corpus callosum
BAP1	253	ubiquitous	marker	left testis, right testis, right frontal lobe

Protein interactions among cohort

Intra-cohort edges: 13.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TERT	5,717
ERBB3	4,511
RNF2	3,814
GNAQ	3,480
EIF1AX	3,407
BAP1	3,373
HERC2	2,843
SLTM	2,598
OCA2	2,132
DDX43	2,049

Intra-cohort edges

A	B	Sources
BAP1	EIF1AX	string_interaction
BAP1	GNA11	string_interaction
BAP1	GNAQ	string_interaction
BAP1	PLCB4	string_interaction
CLPTM1L	TERT	string_interaction
EIF1AX	ERBB3	biogrid_interaction
EIF1AX	GNA11	string_interaction
EIF1AX	GNAQ	string_interaction
EIF1AX	PLCB4	string_interaction
GNA11	GNAQ	string_interaction
GNA11	PLCB4	string_interaction
GNAQ	PLCB4	string_interaction
HERC2	OCA2	string_interaction

Structural data

PDB: 9 · AlphaFold-only: 6 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNAQ	P50148	37
EIF1AX	P47813	29
ERBB3	P21860	23
TERT	O14746	23
MAGI1	Q96QZ7	16
RNF2	Q99496	15
HERC2	O95714	15
GNA11	P29992	13
BAP1	Q92560	4

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PLCB4	Q15147	86.03
DDX43	Q9NXZ2	80.28
CLPTM1L	Q96KA5	78.54
TMEM127	O75204	77.38
OCA2	Q04671	73.79
SLTM	Q9NWH9	52.38

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 69. Enrichment computed across 15 evidence-associated genes (10 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 10 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
PLC beta mediated events	3	79.7×	4e-04	GNA11, GNAQ, PLCB4
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion	2	285.5×	7e-04	GNA11, GNAQ
Acetylcholine regulates insulin secretion	2	228.4×	7e-04	GNA11, GNAQ
G-protein activation	2	95.2×	0.002	GNA11, GNAQ
Thromboxane signalling through TP receptor	2	95.2×	0.002	GNA11, GNAQ
ADP signalling through P2Y purinoceptor 1	2	91.4×	0.002	GNA11, GNAQ
Thrombin signalling through proteinase activated receptors (PARs)	2	71.4×	0.003	GNA11, GNAQ
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	2	71.4×	0.003	GNA11, GNAQ
Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding	2	60.1×	0.004	GNA11, GNAQ
G alpha (q) signalling events	3	17.2×	0.004	GNA11, GNAQ, PLCB4
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	2	32.2×	0.010	GNA11, GNAQ
SUMOylation of DNA damage response and repair proteins	2	29.3×	0.011	RNF2, HERC2
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	2	29.3×	0.011	HERC2, BAP1
Melanin biosynthesis	1	228.4×	0.022	OCA2
GRB7 events in ERBB2 signaling	1	190.3×	0.024	ERBB3
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	163.1×	0.026	TERT
Downregulation of ERBB2:ERBB3 signaling	1	81.6×	0.047	ERBB3
ERBB2 Activates PTK6 Signaling	1	81.6×	0.047	ERBB3
ERBB2 Regulates Cell Motility	1	71.4×	0.049	ERBB3
PI3K events in ERBB2 signaling	1	67.2×	0.049	ERBB3
SUMOylation of DNA methylation proteins	1	67.2×	0.049	RNF2
Extension of Telomeres	1	60.1×	0.052	TERT
SHC1 events in ERBB2 signaling	1	47.6×	0.057	ERBB3
DNA Double Strand Break Response	1	47.6×	0.057	BAP1
Signaling by ERBB2 TMD/JMD mutants	1	47.6×	0.057	ERBB3
Telomere Extension By Telomerase	1	45.7×	0.058	TERT
Synthesis of IP3 and IP4 in the cytosol	1	42.3×	0.058	PLCB4
Signaling by ERBB2 KD Mutants	1	42.3×	0.058	ERBB3
Downregulation of ERBB2 signaling	1	38.1×	0.062	ERBB3
Telomere Maintenance	1	36.8×	0.062	TERT

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 14 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
entrainment of circadian clock	2	401.2×	0.002	GNA11, GNAQ
phototransduction, visible light	2	185.2×	0.004	GNA11, GNAQ
G protein-coupled acetylcholine receptor signaling pathway	2	150.5×	0.004	GNA11, GNAQ
RNA-templated transcription	1	1203.7×	0.011	TERT
thrombocyte differentiation	1	1203.7×	0.011	BAP1
DNA strand elongation	1	1203.7×	0.011	TERT
nucleate erythrocyte differentiation	1	1203.7×	0.011	BAP1
regulation of melanocyte differentiation	1	1203.7×	0.011	GNA11
siRNA transcription	1	1203.7×	0.011	TERT
phospholipase C-activating endothelin receptor signaling pathway	1	1203.7×	0.011	PLCB4
positive regulation of transdifferentiation	1	1203.7×	0.011	TERT
heart development	3	16.9×	0.011	TERT, ERBB3, GNA11
RNA-templated DNA biosynthetic process	1	601.9×	0.016	TERT
positive regulation of hair cycle	1	601.9×	0.016	TERT
positive regulation of cardiac muscle tissue development	1	601.9×	0.016	ERBB3
leukocyte proliferation	1	601.9×	0.016	BAP1
cranial nerve development	1	401.2×	0.021	ERBB3
platelet morphogenesis	1	401.2×	0.021	BAP1
macrophage homeostasis	1	401.2×	0.021	BAP1
melanin biosynthetic process from tyrosine	1	300.9×	0.025	OCA2
phospholipase C-activating G protein-coupled glutamate receptor signaling pathway	1	300.9×	0.025	GNAQ
lysosomal lumen pH elevation	1	240.7×	0.027	OCA2
negative regulation of secretion	1	240.7×	0.027	ERBB3
phospholipase C-activating serotonin receptor signaling pathway	1	200.6×	0.027	GNAQ
regulation of platelet activation	1	200.6×	0.027	GNAQ
positive regulation of protein localization to nucleolus	1	200.6×	0.027	TERT
Schwann cell differentiation	1	172.0×	0.027	ERBB3
phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway	1	150.5×	0.027	GNA11
myeloid cell apoptotic process	1	150.5×	0.027	BAP1
developmental pigmentation	1	150.5×	0.027	GNA11

Therapeutics

Drugs indicated for this disease

0 approved, 6 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Dacarbazine	Phase 3 (in late-stage trials)
Melatonin	Phase 3 (in late-stage trials)
Melphalan	Phase 3 (in late-stage trials)
Ranibizumab	Phase 3 (in late-stage trials)
Selumetinib	Phase 3 (in late-stage trials)
Tebentafusp	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Aflibercept, Aldesleukin, Avutometinib, Belinostat, Belzupacap Sarotalocan, Bevacizumab, Binimetinib, Cisplatin, Crizotinib, Entinostat, Epacadostat, Everolimus, Fludarabine, Ipilimumab, Nivolumab, Olaparib, Paclitaxel, Pasireotide, Pembrolizumab, Relatlimab, Sorafenib, Sunitinib, Temozolomide, Trametinib, Tremelimumab, Triamcinolone Acetonide, Vorinostat.

Drug target analysis

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

Druggability breadth: 9 of 15 evidence-associated genes (60%) 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
SLTM	CABOZANTINIB
ERBB3	MOBOCERTINIB
TERT	BERBERINE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ERBB3	23	4
TERT	10	4
SLTM	1	4
RNF2	0	0
DDX43	0	0
EIF1AX	0	0
GNA11	0	0
GNAQ	0	0
CLPTM1L	0	0
TMEM127	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CABOZANTINIB	4	SLTM
MOBOCERTINIB	4	ERBB3
AFATINIB	4	ERBB3
NERATINIB	4	ERBB3
VANDETANIB	4	ERBB3
BOSUTINIB	4	ERBB3
OSIMERTINIB	4	ERBB3
DASATINIB	4	ERBB3
ERLOTINIB	4	ERBB3
LAPATINIB	4	ERBB3
GEFITINIB	4	ERBB3
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
CANERTINIB	3	ERBB3
ROCILETINIB	3	ERBB3
ALVOCIDIB	3	ERBB3
CEDIRANIB	3	ERBB3
CANERTINIB DIHYDROCHLORIDE	3	ERBB3
LESTAURTINIB	3	ERBB3
RESVERATROL	3	TERT
EPIGALOCATECHIN GALLATE	3	TERT
PERIFOSINE	3	TERT
AEE-788	2	ERBB3
FORETINIB	2	ERBB3
SAPITINIB	2	ERBB3
PF-06459988	2	ERBB3
MAVELERTINIB	2	ERBB3
TOZASERTIB	2	ERBB3
ISOMETAMIDIUM	2	TERT
HOMIDIUM BROMIDE	2	TERT

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

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

Symbol	Assays	Type breakdown
TERT	391	Binding:389, Functional:2
ERBB3	169	Binding:169
GNAQ	27	Binding:27
GNA11	18	Binding:18
RNF2	16	Binding:16
SLTM	14	Binding:14
BAP1	5	Binding:4, Functional:1
MAGI1	4	Binding:4
CLPTM1L	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RNF2	2.3.2.27	RING-type E3 ubiquitin transferase
ERBB3	2.7.10.1	receptor protein-tyrosine kinase
PLCB4	3.1.4.11	phosphoinositide phospholipase C
BAP1	3.4.19.12	ubiquitinyl hydrolase 1

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ERBB3	169
TERT	391

Pharmacogenomics

Cohort genes with a PharmGKB record: 15; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

29 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)
MOBOCERTINIB	4	ERBB3
AFATINIB	4	ERBB3
NERATINIB	4	ERBB3
VANDETANIB	4	ERBB3
BOSUTINIB	4	ERBB3
OSIMERTINIB	4	ERBB3
DASATINIB	4	ERBB3
ERLOTINIB	4	ERBB3
LAPATINIB	4	ERBB3
GEFITINIB	4	ERBB3
BERBERINE	4	TERT
DOXORUBICIN	4	TERT
CANERTINIB	3	ERBB3
ROCILETINIB	3	ERBB3
ALVOCIDIB	3	ERBB3
CEDIRANIB	3	ERBB3
CANERTINIB DIHYDROCHLORIDE	3	ERBB3
LESTAURTINIB	3	ERBB3
RESVERATROL	3	TERT
EPIGALOCATECHIN GALLATE	3	TERT
PERIFOSINE	3	TERT
AEE-788	2	ERBB3
FORETINIB	2	ERBB3
SAPITINIB	2	ERBB3
PF-06459988	2	ERBB3
MAVELERTINIB	2	ERBB3
TOZASERTIB	2	ERBB3
ISOMETAMIDIUM	2	TERT
HOMIDIUM BROMIDE	2	TERT

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	3	SLTM, ERBB3, TERT
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	MAGI1, BAP1
D	Druggable family + AlphaFold only, no drug	2	OCA2, PLCB4
E	Difficult family or no structure, no drug	8	RNF2, DDX43, EIF1AX, GNA11, GNAQ, CLPTM1L, TMEM127, HERC2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CLPTM1L	1	TERT
RNF2	16	—
DDX43	0	—
EIF1AX	0	—
GNA11	18	—
GNAQ	27	—
TMEM127	0	—
HERC2	0	—
OCA2	0	—
PLCB4	0	—
MAGI1	4	—
BAP1	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 194.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	77
PHASE1	41
Not specified	36
PHASE1/PHASE2	20
PHASE3	13
PHASE2/PHASE3	3
PHASE4	2
EARLY_PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00540930	PHASE4	UNKNOWN	Intravitreal Ranibizumab for the Prevention of Radiation Maculopathy Following Plaque Radiotherapy
NCT02379000	PHASE4	UNKNOWN	TTT Versus TTT and Triamcinolone to Decrease Exudation in Choroidal Melanoma After Proton Beam Therapy
NCT05022901	PHASE3	ACTIVE_NOT_RECRUITING	An Open-Label Expanded Access Study of the Melphalan/Hepatic Delivery System (HDS) in Patients With Hepatic Dominant Ocular Melanoma
NCT05502900	PHASE3	RECRUITING	Adjuvant Melatonin for Uveal Melanoma
NCT05987332	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma
NCT06007690	PHASE3	RECRUITING	A Phase 3 Randomized, Masked, Controlled Trial to Evaluate Efficacy and Safety of Belzupacap Sarotalocan (AU-011) Treatment Compared to Sham Control in Subjects With Primary Indeterminate Lesions or Small Choroidal Melanoma
NCT06246149	PHASE3	RECRUITING	Adjuvant Tebentafusp in High Risk Ocular Melanoma
NCT06519266	PHASE3	RECRUITING	PHP in Combination With IPI1/NIVO3 Compared to IPI3/NIVO1 Only in Patients With Uveal Melanoma Liver Metastases
NCT06581406	PHASE2/PHASE3	RECRUITING	A Randomized, Phase 2/3 Study to Investigate the Efficacy and Safety of RP2 in Combination With Nivolumab in Immune Checkpoint Inhibitor-Naïve Adult Patients With Metastatic Uveal Melanoma
NCT07015190	PHASE3	RECRUITING	Neoadjuvant Darovasertib in Primary Uveal Melanoma
NCT00036816	PHASE3	TERMINATED	Vaccine Therapy in Treating Patients With Melanoma of the Eye
NCT00110123	PHASE3	TERMINATED	Intravenous or Hepatic Arterial Infusion of Fotemustine in Treating Patients With Unresectable Liver Metastases From Eye Melanoma
NCT00324727	PHASE3	COMPLETED	Hepatic Arterial Infusion With Melphalan Compared With Standard Therapy in Treating Patients With Unresectable Liver Metastases Due to Melanoma
NCT00811200	PHASE2/PHASE3	UNKNOWN	Treatment Of Radiation Retinopathy Trial
NCT01974752	PHASE3	COMPLETED	Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT)
NCT01983748	PHASE3	COMPLETED	Dendritic Cells Plus Autologous Tumor RNA in Uveal Melanoma
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
NCT02843386	PHASE3	COMPLETED	Comparison Between Fotemustin to Intensive Surveillance in Patients With High Risk Uveal Melanoma
NCT01587352	PHASE2	ACTIVE_NOT_RECRUITING	Vorinostat in Treating Patients With Metastatic Melanoma of the Eye
NCT01979523	PHASE2	ACTIVE_NOT_RECRUITING	Trametinib With or Without GSK2141795 in Treating Patients With Metastatic Uveal Melanoma
NCT02068586	PHASE2	ACTIVE_NOT_RECRUITING	Sunitinib Malate or Valproic Acid in Preventing Metastasis in Patients With High-Risk Uveal 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
NCT03947385	PHASE1/PHASE2	RECRUITING	Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
NCT04645680	PHASE2	ACTIVE_NOT_RECRUITING	Diet and Immune Effects Trial: DIET- A Randomized Double Blinded Dietary Intervention Study in Patients With Metastatic Melanoma Receiving Immunotherapy
NCT04728633	PHASE2	ACTIVE_NOT_RECRUITING	Transarterial Chemoembolization for the Treatment of Uveal Melanoma With Liver Metastases
NCT04802876	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy of Tislelizumab and Spartalizumab Across Multiple Cancer-types in Patients with PD1-high MRNA Expressing Tumors
NCT05170334	PHASE2	ACTIVE_NOT_RECRUITING	Binimetinib Plus Belinostat for Subjects With Metastatic Uveal Melanoma
NCT05282901	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Pembrolizumab in Combination With Lenvatinib in Metastatic Uveal MElanoma Patients (PLUME)
NCT05415072	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Phase I/II Study of DYP688 in Patients With Metastatic Uveal Melanoma and Other GNAQ/11 Mutant Melanomas
NCT05524935	PHASE2	RECRUITING	Olaparib in Combination With Pembrolizumab for Advanced Uveal Melanoma
NCT05893654	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Melphalan Chemoreduction for Ocular Melanoma
NCT05907954	PHASE2	ACTIVE_NOT_RECRUITING	(Neo)Adjuvant IDE196 (Darovasertib) in Patients With Localized Ocular Melanoma
NCT06070012	PHASE2	RECRUITING	Tebentafusp in HLA-A*0201 Positive Previously Untreated Metastatic Uveal Melanoma
NCT06121180	PHASE2	RECRUITING	Study of Cemiplimab Plus Ziv-Aflibercept for Subjects With Metastatic Uveal Melanoma
NCT06626516	PHASE1/PHASE2	RECRUITING	Tebentafusp-tebn With LDT in Metastatic UM
NCT06627244	PHASE2	RECRUITING	Study of Tebentafusp and Radioembolization in the Treatment of Metastatic Uveal Melanoma
NCT06717126	PHASE2	ACTIVE_NOT_RECRUITING	A Randomised Phase II Study of Roginolisib in Patients With Advanced/Metastatic Uveal Melanoma
NCT06932757	PHASE2	RECRUITING	Adjuvant Quisinostat in High-Risk Uveal Melanoma
NCT07063875	PHASE1/PHASE2	RECRUITING	Adding IL-2 to Tebentafusp to Eradicate Cancer Progression
NCT07136181	PHASE1/PHASE2	RECRUITING	Evaluation of the Safety, Efficacy, and Pharmacokinetics of NBM-BMX in Patients With Metastatic Uveal Melanoma

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TEBENTAFUSP	4	8
IPILIMUMAB	4	5
DACARBAZINE	4	4
BINIMETINIB	4	3
CABOZANTINIB	4	3
CRIZOTINIB	4	3
SUNITINIB MALATE	4	3
MELPHALAN	4	2
RANIBIZUMAB	4	2
RELATLIMAB	4	2
SELUMETINIB	4	2
TRAMETINIB	4	2
TRIAMCINOLONE ACETONIDE	4	2
AXITINIB	4	1
BELINOSTAT	4	1
CEMIPLIMAB	4	1
CISPLATIN	4	1
ENTRECTINIB	4	1
ETHIODIZED OIL	4	1
LOMUSTINE	4	1
NIRAPARIB	4	1
PASIREOTIDE	4	1
PEGINTERFERON ALFA-2B	4	1
SARGRAMOSTIM	4	1
SORAFENIB TOSYLATE	4	1
TREMELIMUMAB	4	1
VALACYCLOVIR	4	1
VALPROIC ACID	4	1
VORINOSTAT	4	1
TYROSINASE	3	10

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 18 predictive associations from 18 curated evidence items; also 2 prognostic.

Molecular subtype	Therapy	Effect	Level	CIViC
GNA11 Mutation	Cabozantinib	Sensitivity/Response	CIViC B	EID3049
GNA11 Q209	Selumetinib	Sensitivity/Response	CIViC B	EID1212
GNAQ Mutation	Trametinib	Sensitivity/Response	CIViC B	EID1229
GNAQ Mutation	Cabozantinib	Sensitivity/Response	CIViC B	EID5068
GNAQ Q209	Selumetinib	Sensitivity/Response	CIViC B	EID1213
GNA11 Mutation	Trametinib	Sensitivity/Response	CIViC C	EID1228
GNAQ Q209	Refametinib	Sensitivity/Response	CIViC C	EID1233
MBD4 Frameshift	PD1 Inhibitor	Sensitivity/Response	CIViC C	EID7596
BAP1 Mutation	Trichostatin A + Vorinostat + Panobinostat + Valproic Acid	Sensitivity/Response	CIViC D	EID1234
GNA11 Mutation	JQ1	Sensitivity/Response	CIViC D	EID1211
GNA11 Mutation	Mirdametinib + Sotrastaurin Acetate	Sensitivity/Response	CIViC D	EID1952
GNAQ Mutation	JQ1	Sensitivity/Response	CIViC D	EID1210
GNAQ Mutation	Sotrastaurin Acetate + Mirdametinib	Sensitivity/Response	CIViC D	EID1953
MET Overexpression	Crizotinib	Sensitivity/Response	CIViC D	EID1583
MET Overexpression	C-Met Inhibitor + Mitogen-Activated Protein Kinase Kinase Inhibitor + ERBB3 Inhibitor	Sensitivity/Response	CIViC D	EID3037
DDX43 Overexpression	Trametinib + Mirdametinib + Selumetinib	Resistance	CIViC D	EID1135
ERBB3 Overexpression	Trametinib + Selumetinib	Resistance	CIViC D	EID3050
MET Overexpression	Selumetinib + Trametinib	Resistance	CIViC D	EID3038