Melanoma, uveal, susceptibility to, 2

Summary

Melanoma, uveal, susceptibility to, 2 (MONDO:0011696) is a cancer with 2 cohort genes.

At a glance

• Classification: Cancer
• Cohort genes: 2
• ClinVar variants: 56

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	melanoma, uveal, susceptibility to, 2
Mondo ID	MONDO:0011696
OMIM	606661
UMLS	C1847723
MedGen	339826
GARD	0027803
Is cancer (heuristic)	yes

Also known as: melanoma, uveal, susceptibility to, 2 · melanoma, uveal, susceptibility to, type 2 · UVM2

Data availability: 56 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › susceptibility to uveal melanoma › melanoma, uveal, susceptibility to, 2

Related subtypes (1): melanoma, uveal, susceptibility to, 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

56 retrieved; paginated sample, class counts are floors:

24 benign/likely benign, 14 conflicting classifications of pathogenicity, 8 uncertain significance, 6 pathogenic, 2 benign, 1 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1450488	NM_004656.4(BAP1):c.605G>A (p.Trp202Ter)	BAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
221278	NM_004656.4(BAP1):c.1717del (p.Leu573fs)	BAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
434478	NM_004656.4(BAP1):c.1358_1359del (p.Lys453fs)	BAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
490777	NM_004656.4(BAP1):c.1174C>T (p.Gln392Ter)	BAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
656678	NM_004656.4(BAP1):c.1938T>A (p.Tyr646Ter)	BAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
945509	NM_004656.4(BAP1):c.79del (p.Val27fs)	BAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
3258053	NM_004656.4(BAP1):c.850G>T (p.Glu284Ter)	BAP1	Likely pathogenic	criteria provided, single submitter
240055	NM_004656.4(BAP1):c.2057-4G>T	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
386232	NM_004656.4(BAP1):c.54C>T (p.Leu18=)	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
412427	NM_004656.4(BAP1):c.1212C>G (p.Asp404Glu)	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
412428	NM_004656.4(BAP1):c.1201_1212del (p.Tyr401_Asp404del)	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
472658	NM_004656.4(BAP1):c.1066C>T (p.Arg356Trp)	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
472665	NM_004656.4(BAP1):c.1339G>A (p.Val447Ile)	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
472700	NM_004656.4(BAP1):c.404C>T (p.Pro135Leu)	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
472717	NM_004656.4(BAP1):c.916G>A (p.Glu306Lys)	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
480826	NM_004656.4(BAP1):c.1843A>G (p.Met615Val)	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
485251	NM_004656.4(BAP1):c.1337A>G (p.Asn446Ser)	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
489613	NM_004656.4(BAP1):c.1337A>T (p.Asn446Ile)	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
490767	NM_004656.4(BAP1):c.1060G>A (p.Val354Ile)	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
490880	NM_004656.4(BAP1):c.675C>T (p.Asp225=)	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
841611	NM_004656.4(BAP1):c.487C>T (p.Arg163Trp)	BAP1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1359050	NM_004656.4(BAP1):c.1622T>C (p.Val541Ala)	BAP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2156960	NM_004656.4(BAP1):c.1271G>A (p.Gly424Glu)	BAP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3382818	NM_004656.4(BAP1):c.274G>C (p.Ala92Pro)	BAP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3589467	NM_004656.4(BAP1):c.1343T>G (p.Leu448Trp)	BAP1	Uncertain significance	criteria provided, single submitter
3589469	NM_004656.4(BAP1):c.932-2dup	BAP1	Uncertain significance	criteria provided, single submitter
412440	NM_004656.4(BAP1):c.1148G>A (p.Arg383His)	BAP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
485247	NM_004656.4(BAP1):c.1553G>A (p.Arg518Gln)	BAP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
490807	NM_004656.4(BAP1):c.1715C>T (p.Pro572Leu)	BAP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
133664	NM_004656.4(BAP1):c.1786A>G (p.Ser596Gly)	BAP1	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
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)
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: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	18.3×	0.071
Kinase	1	13.9×	0.071

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
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.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus callosum	1
sural nerve	1
ventricular zone	1
left testis	1
right frontal lobe	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
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: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BAP1	3,373
MAGI1	2,043

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MAGI1	Q96QZ7	16
BAP1	Q92560	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
DNA Double Strand Break Response	1	475.8×	0.013	BAP1
DNA Double-Strand Break Repair	1	248.3×	0.013	BAP1
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	1	146.4×	0.013	BAP1
Deubiquitination	1	124.1×	0.013	BAP1
UCH proteinases	1	124.1×	0.013	BAP1
DNA Repair	1	98.5×	0.014	BAP1
Post-translational protein modification	1	19.2×	0.060	BAP1
Metabolism of proteins	1	12.4×	0.081	BAP1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
thrombocyte differentiation	1	8426.0×	0.002	BAP1
nucleate erythrocyte differentiation	1	8426.0×	0.002	BAP1
leukocyte proliferation	1	4213.0×	0.002	BAP1
platelet morphogenesis	1	2808.7×	0.002	BAP1
macrophage homeostasis	1	2808.7×	0.002	BAP1
myeloid cell apoptotic process	1	1053.2×	0.004	BAP1
neutrophil differentiation	1	936.2×	0.004	BAP1
monoubiquitinated protein deubiquitination	1	936.2×	0.004	BAP1
common myeloid progenitor cell proliferation	1	936.2×	0.004	BAP1
regulation of cytokine production involved in inflammatory response	1	936.2×	0.004	BAP1
endothelial cell morphogenesis	1	526.6×	0.006	MAGI1
erythrocyte maturation	1	421.3×	0.007	BAP1
positive regulation of cell-cell adhesion	1	383.0×	0.007	MAGI1
protein K48-linked deubiquitination	1	324.1×	0.007	BAP1
tissue homeostasis	1	280.9×	0.008	BAP1
hematopoietic stem cell homeostasis	1	280.9×	0.008	BAP1
obsolete positive regulation of protein targeting to mitochondrion	1	247.8×	0.008	BAP1
neuron cellular homeostasis	1	227.7×	0.008	BAP1
heterochromatin formation	1	127.7×	0.014	BAP1
protein modification process	1	122.1×	0.014	BAP1
regulation of cell growth	1	110.9×	0.015	BAP1
protein deubiquitination	1	88.7×	0.017	BAP1
regulation of inflammatory response	1	84.3×	0.017	BAP1
mitotic cell cycle	1	66.9×	0.021	BAP1
protein-containing complex assembly	1	56.9×	0.024	MAGI1
gene expression	1	39.9×	0.032	BAP1
regulation of cell cycle	1	37.3×	0.032	BAP1
ubiquitin-dependent protein catabolic process	1	37.1×	0.032	BAP1
in utero embryonic development	1	36.0×	0.032	BAP1
cell surface receptor signaling pathway	1	32.0×	0.035	MAGI1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MAGI1	0	0
BAP1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
BAP1	5	Binding:4, Functional:1
MAGI1	4	Binding:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BAP1	3.4.19.12	ubiquitinyl hydrolase 1

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	2	MAGI1, BAP1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MAGI1	4	—
BAP1	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.