BBC3
protein-codingBCL2 binding component 3, the group of MicroRNA protein coding host genes|BCL2 homology region 3 (BH3) only
Gene summary
This gene encodes a member of the BCL-2 family of proteins. This family member belongs to the BH3-only pro-apoptotic subclass. The protein cooperates with direct activator proteins to induce mitochondrial outer membrane permeabilization and apoptosis. It can bind to anti-apoptotic Bcl-2 family members to induce mitochondrial dysfunction and caspase activation. Because of its pro-apoptotic role, this gene is a potential drug target for cancer therapy and for tissue injury. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.9 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 BBC3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014417.5. 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 | 17 | 1 | 18 | |||
| missense | 12 | 15 | 27 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 33 | 16 | 0 | 49 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055232.1 | 3 | MANE Select | |
| Ensembl | ENSP00000395862.2 | 3 | MANE Select | |
| RefSeq | NP_001120712.1 | 4 | Standard | |
| RefSeq | NP_001120713.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- p53 signaling pathway - Homo sapiens (human)
- Apoptosis - multiple species - Homo sapiens (human)
- Huntington,s disease - Homo sapiens (human)
- Hippo signaling pathway - Homo sapiens (human)
- Pathways in cancer - Homo sapiens (human)
Biological Process
- release of cytochrome c from mitochondria
- apoptotic process
- activation of cysteine-type endopeptidase activity involved in apoptotic process
- positive regulation of apoptotic process
- intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
Molecular Function
- protein binding
- ATPase binding
Cellular Component
- mitochondrion
- lysosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000449228
- Coding exons
- 4
- Length
- 11943
- Individuals with no LoFs
- 124132
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 38
- Defined
- 124170
- p
- 0.000153
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.155 | 80 | 84.0 | 0.953 | 0.00000459 | 1559 |
| Missense (PolyPhen) | 18 | 15.666 | 1.149 | 153 | ||
| Synonymous | 0.548 | 33 | 37.3 | 0.886 | 0.00000220 | 657 |
| Loss of Function | 0.593 | 4 | 5.50 | 0.727 | 3.31e-7 | 81 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00024 | 0.00024 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Isoform 3: Does not affect cell growth. {ECO:0000269|PubMed:11463392}.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.781
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |