BAP1

BRCA1 associated protein 1, the group of Ubiquitin C-terminal hydrolases

Basic information

Region (hg38): 3:52401007-52410008

Links

ENSG00000163930 ∙ NCBI:8314 ∙ OMIM:603089 ∙ HGNC:950 ∙ Uniprot:Q92560 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• BAP1-related tumor predisposition syndrome (Strong), mode of inheritance: AD
• renal cell carcinoma (Strong), mode of inheritance: AD
• BAP1-related tumor predisposition syndrome (Strong), mode of inheritance: AD
• BAP1-related tumor predisposition syndrome (Definitive), mode of inheritance: AD
• BAP1-related tumor predisposition syndrome (Supportive), mode of inheritance: AD
• Kury-Isidor syndrome (Strong), mode of inheritance: AD
• BAP1-related tumor predisposition syndrome (Definitive), mode of inheritance: AD
• BAP1-related tumor predisposition syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tumor predisposition syndrome 1	AD	Dermatologic; Oncologic	Awareness of oncologic risk may allow surveillance for and early treatment of a variety of malignancies (including uveal and cutaneous melanomas, mesothelioma, and several other types of cancer), which may reduce morbidity and mortality	Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Oncologic	21941004; 21874000 21874003; 23032617; 23341325; 35051358

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BAP1 gene.

• BAP1-related tumor predisposition syndrome (1794 variants)
• Hereditary cancer-predisposing syndrome (1606 variants)
• not provided (321 variants)
• not specified (127 variants)
• Melanoma, uveal, susceptibility to, 2 (26 variants)
• BAP1-related condition (11 variants)
• Neurodevelopmental disorder (7 variants)
• Kury-Isidor syndrome;BAP1-related tumor predisposition syndrome (6 variants)
• Kury-Isidor syndrome (6 variants)
• BAP1-related tumor predisposition syndrome;Kury-Isidor syndrome (4 variants)
• Uveal melanoma (2 variants)
• Inborn genetic diseases (2 variants)
• Ewing sarcoma (1 variants)
• Kury-Isidor syndrome;Melanoma, uveal, susceptibility to, 2;BAP1-related tumor predisposition syndrome (1 variants)
• Hereditary cancer (1 variants)
• Clear cell carcinoma of kidney (1 variants)
• See cases (1 variants)
• Ganglioglioma (1 variants)
• BAP1 Cancer Syndrome (1 variants)
• Medulloblastoma (1 variants)
• Adenoid cystic carcinoma (1 variants)
• BAP1-associated neurodevelopmental disorder (1 variants)
• Astrocytoma (1 variants)
• Familial melanoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BAP1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	572	2	578
missense	2	6	1003	11	1	1023
nonsense	54	5	2	1		62
start loss	1	2				3
frameshift	135	12	1			148
inframe indel			19			19
splice donor/acceptor (+/-2bp)	15	51	4			70
splice region		1	68	82		151
non coding			47	289	11	347
Total	207	76	1080	873	14

Highest pathogenic variant AF is 0.0000788

Variants in BAP1

This is a list of pathogenic ClinVar variants found in the BAP1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-52401124-C-A		BAP1-related tumor predisposition syndrome	Uncertain significance (Jan 13, 2018)
3-52401124-C-G		BAP1-related tumor predisposition syndrome	Benign (Jan 13, 2018)
3-52401224-G-A		BAP1-related tumor predisposition syndrome	Uncertain significance (Jan 12, 2018)
3-52401314-G-A		BAP1-related tumor predisposition syndrome	Benign (Jan 12, 2018)
3-52401412-G-A		BAP1-related tumor predisposition syndrome	Uncertain significance (Jan 13, 2018)
3-52401441-G-A		BAP1-related tumor predisposition syndrome	Uncertain significance (Jan 13, 2018)
3-52401458-A-G		BAP1-related tumor predisposition syndrome	Uncertain significance (Jan 13, 2018)
3-52401480-A-G		BAP1-related tumor predisposition syndrome	Uncertain significance (Feb 09, 2018)
3-52401518-A-G		BAP1-related tumor predisposition syndrome	Uncertain significance (Jan 12, 2018)
3-52401538-T-C		BAP1-related tumor predisposition syndrome	Uncertain significance (Jan 13, 2018)
3-52401591-C-T		BAP1-related tumor predisposition syndrome	Uncertain significance (Jan 12, 2018)
3-52401645-C-T		BAP1-related tumor predisposition syndrome • BAP1-related disorder	Benign/Likely benign (May 30, 2023)
3-52401647-G-A		BAP1-related disorder	Uncertain significance (Dec 04, 2023)
3-52401715-C-T		BAP1-related tumor predisposition syndrome	Benign (Jan 13, 2018)
3-52401731-G-A		BAP1-related tumor predisposition syndrome	Uncertain significance (Jan 12, 2018)
3-52401736-G-T		BAP1-related tumor predisposition syndrome	Uncertain significance (Jan 13, 2018)
3-52401803-C-A		BAP1-related tumor predisposition syndrome	Uncertain significance (Jan 12, 2018)
3-52401844-G-A		BAP1-related tumor predisposition syndrome	Likely benign (Jun 15, 2019)
3-52401847-C-A		BAP1-related tumor predisposition syndrome	Likely benign (Jan 12, 2018)
3-52401896-G-A		BAP1-related tumor predisposition syndrome	Benign/Likely benign (Jun 15, 2019)
3-52401903-T-A		BAP1-related tumor predisposition syndrome	Benign (Jan 13, 2018)
3-52401938-G-T		BAP1-related tumor predisposition syndrome	Uncertain significance (Jan 13, 2018)
3-52401988-T-C		BAP1-related tumor predisposition syndrome	Benign (Jan 13, 2018)
3-52401996-C-T		BAP1-related tumor predisposition syndrome	Uncertain significance (Jan 13, 2018)
3-52402066-C-G		BAP1-related tumor predisposition syndrome	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BAP1	protein_coding	protein_coding	ENST00000460680	17	9338

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.994	0.00557	125702	0	44	125746	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.64	277	432	0.642	0.0000280	4739
Missense in Polyphen		70	167.8	0.41715		1809
Synonymous	0.179	176	179	0.983	0.0000118	1469
Loss of Function	4.68	4	33.0	0.121	0.00000164	404

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000467	0.000467
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000188	0.000185
Middle Eastern	0.000109	0.000109
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A and HCFC1. Catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1). Does not deubiquitinate monoubiquitinated histone H2B. Acts as a regulator of cell growth by mediating deubiquitination of HCFC1 N-terminal and C-terminal chains, with some specificity toward 'Lys-48'- linked polyubiquitin chains compared to 'Lys-63'-linked polyubiquitin chains. Deubiquitination of HCFC1 does not lead to increase stability of HCFC1. Interferes with the BRCA1 and BARD1 heterodimer activity by inhibiting their ability to mediate ubiquitination and autoubiquitination. It however does not mediate deubiquitination of BRCA1 and BARD1. Able to mediate autodeubiquitination via intramolecular interactions to couteract monoubiquitination at the nuclear localization signal (NLS), thereby protecting it from cytoplasmic sequestration (PubMed:24703950). Acts as a tumor suppressor. {ECO:0000269|PubMed:12485996, ECO:0000269|PubMed:18757409, ECO:0000269|PubMed:19117993, ECO:0000269|PubMed:19188440, ECO:0000269|PubMed:19815555, ECO:0000269|PubMed:20436459, ECO:0000269|PubMed:24703950, ECO:0000269|PubMed:9528852}.
• Disease: DISEASE: Mesothelioma, malignant (MESOM) [MIM:156240]: An aggressive neoplasm of the serosal lining of the chest. It appears as broad sheets of cells, with some regions containing spindle- shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. {ECO:0000269|PubMed:21642991, ECO:0000269|PubMed:21874000}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Tumor predisposition syndrome (TPDS) [MIM:614327]: A condition characterized by predisposition to develop a variety of tumors, including benign melanocytic tumors as well as several malignant tumors, including uveal melanoma, cutaneous melanoma, malignant mesothelioma on exposure to asbestos, lung adenocarcinoma and meningioma. {ECO:0000269|PubMed:21874000, ECO:0000269|PubMed:21874003}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pathways in clear cell renal cell carcinoma;DNA Repair;DNA Double-Strand Break Repair;Post-translational protein modification;Metabolism of proteins;UCH proteinases;Deubiquitination;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response (Consensus)

Recessive Scores

• pRec: 0.106

Intolerance Scores

• loftool: 0.364
• rvis_EVS: -0.98
• rvis_percentile_EVS: 8.85

Haploinsufficiency Scores

• pHI: 0.272
• hipred: Y
• hipred_score: 0.756
• ghis: 0.600

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.689

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Bap1
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); neoplasm; embryo phenotype; respiratory system phenotype; immune system phenotype; digestive/alimentary phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: bap1
• Affected structure: neuron
• Phenotype tag: abnormal
• Phenotype quality: hyperplastic

Gene ontology

• Biological process: regulation of cell growth;cellular protein modification process;ubiquitin-dependent protein catabolic process;negative regulation of cell population proliferation;response to inorganic substance;protein deubiquitination;monoubiquitinated protein deubiquitination;monoubiquitinated histone H2A deubiquitination;regulation of cell cycle;macrophage homeostasis;protein K48-linked deubiquitination;regulation of cytokine production involved in inflammatory response;positive regulation of protein targeting to mitochondrion
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;PR-DUB complex
• Molecular function: chromatin binding;thiol-dependent ubiquitin-specific protease activity;protein binding;peptidase activity;thiol-dependent ubiquitinyl hydrolase activity