BAK1
protein-codingBCL2 antagonist/killer 1, the group of BCL2 family
Gene summary
The protein encoded by this gene belongs to the BCL2 protein family. BCL2 family members form oligomers or heterodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein localizes to mitochondria, and functions to induce apoptosis. It interacts with and accelerates the opening of the mitochondrial voltage-dependent anion channel, which leads to a loss in membrane potential and the release of cytochrome c. This protein also interacts with the tumor suppressor P53 after exposure to cell stress. [provided by RefSeq, Jul 2008]
- CDN1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to BAK1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001188.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 24 | 1 | 1 | 26 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 30 | 1 | 1 | 32 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001179.1 | 5 | MANE Select | |
| Ensembl | ENSP00000363591.3 | 5 | MANE Select | |
| Ensembl | ENSP00000391258.2 | 5 | Standard | |
| Ensembl | ENSP00000391258.2 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Non-small cell lung cancer - Homo sapiens (human)
- Chronic myeloid leukemia - Homo sapiens (human)
- Gastric cancer - Homo sapiens (human)
- Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human)
- Melanoma - Homo sapiens (human)
Biological Process
- B cell homeostasis
- B cell apoptotic process
- release of cytochrome c from mitochondria
- blood vessel remodeling
- myeloid cell homeostasis
Molecular Function
- molecular_function
- protein binding
- heat shock protein binding
- identical protein binding
- protein homodimerization activity
Cellular Component
- mitochondrion
- mitochondrial outer membrane
- endoplasmic reticulum
- cytosol
- integral component of mitochondrial outer membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374467
- Coding exons
- 5
- Length
- 7691
- Individuals with no LoFs
- 125720
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 28
- Defined
- 125748
- p
- 0.000111
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.991 | 102 | 134 | 0.759 | 0.00000839 | 1357 |
| Missense (PolyPhen) | 26 | 31.756 | 0.81873 | 326 | ||
| Synonymous | 0.879 | 44 | 52.1 | 0.845 | 0.00000314 | 442 |
| Loss of Function | 0.670 | 9 | 11.4 | 0.786 | 5.78e-7 | 110 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000088 | 0.000088 | rare |
| South Asian | 0.00029 | 0.00029 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a role in the mitochondrial apoptosic process. Upon arrival of cell death signals, promotes mitochondrial outer membrane (MOM) permeabilization by oligomerizing to form pores within the MOM. This releases apoptogenic factors into the cytosol, including cytochrome c, promoting the activation of caspase 9 which in turn processes and activates the effector caspases. {ECO:0000269|PubMed:17157251, ECO:0000269|PubMed:8521816}.;
Recessive Scores
- pRec
- 0.417
Intolerance Scores
- LoFtool
- 0.737
- RVIS EVS
- -0.32
- RVIS percentile EVS
- 31.46
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.984
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |