BCL2L1
protein-codingBCL2 like 1, the group of BCL2 family|Protein phosphatase 1 regulatory subunits
Gene summary
The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The proteins encoded by this gene are located at the outer mitochondrial membrane, and have been shown to regulate outer mitochondrial membrane channel (VDAC) opening. VDAC regulates mitochondrial membrane potential, and thus controls the production of reactive oxygen species and release of cytochrome C by mitochondria, both of which are the potent inducers of cell apoptosis. Alternative splicing results in multiple transcript variants encoding two different isoforms. The longer isoform acts as an apoptotic inhibitor and the shorter isoform acts as an apoptotic activator. [provided by RefSeq, Dec 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~59.5 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 BCL2L1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_138578.3. 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 | 2 | 2 | ||||
| missense | 9 | 9 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 9 | 2 | 0 | 11 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_612815.1 | 2 | MANE Select | |
| Ensembl | ENSP00000302564.4 | 2 | MANE Select | |
| RefSeq | NP_001182.1 | 2 | Standard | |
| RefSeq | NP_001304848.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| bcl2l1 | Danio rerio | Structure: whole organism Quality: lacks all parts of type abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Chronic myeloid leukemia - Homo sapiens (human)
- Jak-STAT signaling pathway - Homo sapiens (human)
- Small cell lung cancer - Homo sapiens (human)
- Apoptosis - multiple species - Homo sapiens (human)
Biological Process
- ovarian follicle development
- in utero embryonic development
- release of cytochrome c from mitochondria
- endocytosis
- mitotic cell cycle checkpoint
Molecular Function
- protein binding
- protein kinase binding
- identical protein binding
- protein homodimerization activity
- protein heterodimerization activity
Cellular Component
- cytoplasm
- mitochondrion
- mitochondrial outer membrane
- mitochondrial inner membrane
- mitochondrial matrix
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000307677
- Coding exons
- 2
- Length
- 59538
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.62 | 91 | 146 | 0.623 | 0.00000898 | 1535 |
| Missense (PolyPhen) | 7 | 35.018 | 0.1999 | 428 | ||
| Synonymous | 0.547 | 57 | 62.5 | 0.912 | 0.00000400 | 473 |
| Loss of Function | 2.74 | 0 | 8.76 | 0.00 | 4.62e-7 | 81 |
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 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Potent inhibitor of cell death. Inhibits activation of caspases. Appears to regulate cell death by blocking the voltage- dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.; FUNCTION: Isoform Bcl-X(S) promotes apoptosis.;
Recessive Scores
- pRec
- 0.758
Intolerance Scores
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 38.28
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Low | Medium |