BAP1

BRCA1 associated deubiquitinase 1

7 disorders 6 untyped 1 somatic driver 3p21.1 gene with protein product

HGNC:950 Monarch NCBI Gene 8314 ENSG00000163930 UniProt Q92560 OMIM 603089

Aliases: hucep-6, KIAA0272, UCHL2.

Normal function · from ai-gene-review (Q92560, commit 79fe13b38970) · AI-generated, not KB evidence

BAP1 is a ubiquitin C-terminal hydrolase with an active-site cysteine and a major role in chromatin regulation. In nuclear PR-DUB complexes, ASXL proteins activate BAP1 to remove monoubiquitin from histone H2A lysine 119. Engagement with nucleosomal DNA, histones and ubiquitin establishes substrate recognition. This reaction regulates transcription, with activating or repressive consequences depending on the locus and cellular context. BAP1 also deubiquitinates nonhistone proteins, including the nuclear transcriptional coregulator HCFC1 and the endoplasmic-reticulum calcium channel ITPR3. Its regulated nuclear and cytoplasmic distribution connects these substrate-specific activities to cell growth, genome maintenance and cell-death responses. Germline and somatic BAP1 variants are associated with tumor predisposition and, for some germline missense variants, neurodevelopmental disease.

BAP1 catalyzes removal of monoubiquitin from histone H2A lysine 119 in nuclear PR-DUB complexes. ASXL proteins activate the enzyme, while contacts with nucleosomal DNA, histones and ubiquitin position the substrate. This chromatin reaction regulates transcription, with activating or repressive outcomes determined by the locus and cellular context.

molecular function: histone H2A deubiquitinase activity · directly involved in: regulation of DNA-templated transcription · locations: nucleus · in complex: PR-DUB complex

BAP1 also catalyzes deubiquitination of nonhistone regulatory proteins. Nuclear HCFC1 is an established substrate, whereas an ER-associated BAP1 pool deubiquitinates ITPR3 and supports receptor stability and calcium-dependent cell-death responses. Substrate stabilization is context dependent and is not a universal consequence of BAP1 catalysis.

molecular function: cysteine-type deubiquitinase activity · directly involved in: protein deubiquitination · locations: nucleus; endoplasmic reticulum

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Ocular Melanoma	somatic driver germline and somatic	mechanism: BAP1 Loss with Monosomy 3 subtype: Uveal Melanoma scoped to subtype: Uveal Melanoma
Clear Cell Renal Cell Carcinoma	untyped Somatic Inactivating Mutations
IDH-Mutant Cholangiocarcinoma	untyped Co-occurring Mutations
Malignant Mesothelioma	untyped Germline and Somatic Mutations	mechanism: BAP1 Tumor Suppressor Inactivation
Malignant Peritoneal Mesothelioma	untyped Recurrent Loss-of-Function Alteration somatic	mechanism: BAP1 Tumor Suppressor Inactivation
Renal Cell Carcinoma	untyped Somatic loss of function
Uveal Melanoma	untyped Somatic Tumor Suppressor Loss

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
BAP1-related tumor predisposition syndrome MONDO:0013692	AD	Definitive 2019-03-21	no dismech entry

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.