BCL2
protein-codingBCL2 apoptosis regulator, the group of BCL2 family|Protein phosphatase 1 regulatory subunits
Gene summary
This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~196.8 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 BCL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000633.3. 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 | 1 | 1 | 2 | |||
| missense | 12 | 12 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 12 | 1 | 1 | 14 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000624.2 | 2 | MANE Select | |
| Ensembl | ENSP00000329623.3 | 2 | MANE Select | |
| RefSeq | NP_000648.2 | 1 | Standard | |
| RefSeq | NP_001425864.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Gastric cancer - Homo sapiens (human)
- Focal adhesion - Homo sapiens (human)
- Neurotrophin signaling pathway - Homo sapiens (human)
- AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
Biological Process
- protein polyubiquitination
- ossification
- ovarian follicle development
- metanephros development
- branching involved in ureteric bud morphogenesis
Molecular Function
- protease binding
- protein binding
- transcription factor binding
- channel activity
- channel inhibitor activity
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- mitochondrion
- mitochondrial outer membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000398117
- Coding exons
- 2
- Length
- 196783
- Individuals with no LoFs
- 117770
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 117772
- p
- 0.00000849
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.40 | 94 | 141 | 0.668 | 0.00000669 | 1518 |
| Missense (PolyPhen) | 29 | 60.607 | 0.47849 | 662 | ||
| Synonymous | -0.283 | 67 | 64.1 | 1.04 | 0.00000309 | 523 |
| Loss of Function | 2.03 | 1 | 6.66 | 0.150 | 2.88e-7 | 65 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000019 | 0.000019 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785). {ECO:0000269|PubMed:17418785, ECO:0000269|PubMed:18570871}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions. {ECO:0000269|PubMed:2875799, ECO:0000269|PubMed:3285301}.;
Recessive Scores
- pRec
- 0.983
Intolerance Scores
- LoFtool
- 0.238
- RVIS EVS
- -0.19
- RVIS percentile EVS
- 39.68
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |