BAP1 Gene (BRCA1 Associated Protein 1)
Tumor Suppressor Gene Involved in Chromatin Regulation and DNA Repair
Gene Information Card
| Symbol | BAP1 |
|---|---|
| Full Name | BRCA1 Associated Protein 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.1 |
| NCBI Gene ID | 8314 ncbi.nlm.nih.gov/gene/8314 |
| Ensembl ID | ENSG00000163930 |
| UniProt ID | Q92560 |
| OMIM ID | 603089 |
| HGNC ID | HGNC:950 |
| Aliases | UCHL2, hucep-6, KIAA0272 |
Description
BAP1 (BRCA1 Associated Protein 1) is a tumor suppressor gene encoding a nuclear deubiquitinating enzyme that belongs to the ubiquitin C-terminal hydrolase (UCH) subfamily. The protein interacts with BRCA1 via its RING finger domain and functions in chromatin remodeling, DNA damage repair, cell cycle regulation, and apoptosis. Germline mutations in BAP1 predispose to BAP1 tumor predisposition syndrome (TPDS), characterized by increased risk of uveal melanoma, malignant mesothelioma, cutaneous melanoma, and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| BAP1 tumor predisposition syndrome | Germline loss-of-function mutations lead to haploinsufficiency and impaired tumor suppression | OMIM #614327; ClinVar |
| Uveal melanoma | Somatic or germline BAP1 mutations result in loss of deubiquitinase activity and chromatin dysregulation | COSMIC; NCBI PubMed |
| Malignant mesothelioma | Biallelic inactivation of BAP1 via mutation or deletion promotes tumorigenesis | ClinVar; COSMIC |
| Cutaneous melanoma | Germline BAP1 mutations increase susceptibility; somatic mutations found in sporadic cases | OMIM; NCBI Gene |
| Renal cell carcinoma | BAP1 mutations are associated with aggressive clear cell RCC | COSMIC; ClinVar |
| Breast cancer | BAP1 interacts with BRCA1; loss may contribute to DNA repair defects | NCBI PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.5 | Medium |
| Testis | 10.8 | Medium |
| Brain | 8.2 | Low |
| Liver | 7.9 | Low |
| Kidney | 6.4 | Low |
| Heart | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung carcinoma) | 15.3 | High expression |
| HeLa (cervical carcinoma) | 12.1 | Medium expression |
| MCF7 (breast carcinoma) | 9.8 | Medium expression |
| HEK293 (embryonic kidney) | 8.5 | Low expression |
| HepG2 (hepatocellular carcinoma) | 7.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1717delC (p.Leu573Trpfs*3) | Frameshift | Germline; 5-10% in TPDS | Loss of function |
| c.205G>T (p.Glu69*) | Nonsense | Somatic; ~3% in uveal melanoma | Loss of function |
| c.581A>G (p.His194Arg) | Missense | Somatic; rare | Loss of function |
| c.1780C>T (p.Arg594*) | Nonsense | Germline; 2-5% in TPDS | Loss of function |
| c.2000_2001insA (p.Tyr667*) | Frameshift | Somatic; ~2% in mesothelioma | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most BAP1 mutations are loss-of-function, including nonsense, frameshift, splice site, and missense variants that impair deubiquitinase activity or protein stability. These lead to haploinsufficiency or complete loss of BAP1 function.
Gain of Function (GOF)
No gain-of-function mutations have been reported for BAP1.
Dominant Negative (DN)
Dominant-negative effects are not well established; however, some missense mutations may interfere with wild-type BAP1 function in heterozygous state.
View complete mutation data：
Gene Ontology (GO)
| • thiol-dependent deubiquitinase (GO:0004843) | • nucleus (GO:0005634) |
| • chromatin organization (GO:0006325) | • DNA repair (GO:0006281) |
| • cellular response to DNA damage stimulus (GO:0006974) | • cell cycle (GO:0007049) |
| • apoptotic process (GO:0006915) | • protein deubiquitination (GO:0016579) |
| • intracellular ribonucleoprotein complex (GO:0030529) | • intracellular membrane-bounded organelle (GO:0043231) |
Pathways
• Ubiquitin-proteasome pathway
• BRCA1-mediated DNA damage repair
• Chromatin remodeling via H2A deubiquitination
• Cell cycle checkpoint control
• Apoptosis signaling
Protein Summary
The BAP1 protein (UniProt Q92560) is a 729-amino acid nuclear deubiquitinase with an N-terminal UCH domain responsible for cleaving ubiquitin from target proteins, and a C-terminal domain that mediates interaction with BRCA1, HCFC1, and other chromatin-associated factors. BAP1 regulates gene expression by deubiquitinating histone H2A at lysine 119, thereby modulating chromatin structure and transcription. It also plays a critical role in the DNA damage response by facilitating homologous recombination repair. Loss of BAP1 function leads to genomic instability, altered cell proliferation, and increased cancer susceptibility.
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