• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
BAP1 (HGNC:950) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
BRCA1 associated protein 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
hucep-6, KIAA0272, UCHL2
%HI
18.49(Read more about the DECIPHER Haploinsufficiency Index)
pLI
0.99(Read more about gnomAD pLI score)
LOEUF
0.28(Read more about gnomAD LOEUF score)
Cytoband
3p21.1
Genomic Coordinates
GRCh37/hg19: chr3:52435024-52444024 NCBI Ensembl UCSC
GRCh38/hg38: chr3:52401008-52410008 NCBI Ensembl UCSC
MANE Select Transcript
NM_004656.4 ENST00000460680.6 (Read more about MANE Select)
Function
Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A and HCFC1 (PubMed:12485996, PubMed:18757409, PubMed:20436459, PubMed:25451922, PubMed:35051358). Catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1) (PubMed:20436459, PubMed:25451922, PubMed:35051358). Does not deubiquitinate monoubiquitinated histone H2B (PubMed:20436459). Acts as a regulat... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-11816
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
12/27/2019

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • BAP1 Tumor Predisposition Syndrome Monarch
HI Evidence:
  • PUBMED: 21874000
    Testa et al 2011 identified two families with high incidence of mesothelioma and sequenced for causal germline variants. Two germline truncating variants (nonsense and splice) were identified. Family L 9 segregations of BAP1 Exon 16 (52,436,624 C>T, nonsense) with various implicated cancers including mesothelioma, uveal melanoma, pancreatic cancer and skin cancer. Family W has 7 segregations of BAP1 Intron 6 (52,441,334 A>G-splice site) with cancers of mesothelioma, breast, renal and ovarian. 7 cancer samples for these families were tested as well, and 4 of the 7 revealed second hits in BAP1, with loss of heterozygosity in regions encompassing BAP1 or no expression of BAP1. 3 tumor samples were not determined. This emphasizes the likely two-hit nature of BAP1, in that a single inherited germline mutations in BAP1 would not alone be causal in cancer, but combined with a loss or mutation event of the second allele would cause a cancer phenotype.
  • PUBMED: 21941004
    Abdel-Rahman 2013 identified a BAP1 nonsense mutation Q267X in a family with 6 segregations and cancers of uveal melanoma, mesothelioma, meningioma and lung adenocarcinoma. In three family members, tumor samples were available and all had loss of heterogyzosity including BAP1. This indicates that the tumor phenotype is expressed upon bi-allelic inactivation of BAP1.
  • PUBMED: 21874003
    Weisner et al reports on two families with melanocytic tumors displaying BAP1 mutations. In family 1 three segregations of a frameshift mutation in BAP1 (c.1305delG, p.Gln436Asnfs*135) were identified. BAP1 presence was queried in 29 skin tumors and uveal melanoma samples, and all displayed loss of wildtype BAP1. Family 2 carried a splice mutation that removed the acceptor splice site at the last exon (c.2057-2A>G, p.Met687Glufs*28), which was confirmed by cDNA as a splicing mutation that failed to remove the last intron of BAP1. This pedigree displays 5 segregations. In 9/13 tumors, wildtype BAP1 was lost.
HI Evidence Comments:
Haploinsufficiency results in BAP1 Tumor Predisposition Syndrome. See also PMID:30883995 on BAP1 gene deletion and uveal melanoma. https://www.ncbi.nlm.nih.gov/pubmed/30883995

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Literature search did not reveal supporting evidence of publications reporting BAP1 gains. No BAP1 CNV gains were identified in the UCSC Genome Browser, or COSMIC. A ClinVar record (Variation ID: 539946) describes a gross gain encompassing BAP1 with unknown start and end points, this is classified as Uncertain Significance. https://www.ncbi.nlm.nih.gov/clinvar/variation/539946/#summary-evidence

Genomic View

Select assembly: (NC_000003.11) (NC_000003.12)