BCL2L11
protein-codingBCL2 like 11, the group of BCL2 homology region 3 (BH3) only
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 protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1, which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~49.1 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 BCL2L11 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_138621.5. 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 | 1 | 1 | 2 | |||
| missense | 25 | 25 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 29 | 1 | 1 | 31 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_619527.1 | 3 | MANE Select | |
| Ensembl | ENSP00000376943.2 | 3 | MANE Select | |
| RefSeq | NP_001191035.1 | 3 | Standard | |
| RefSeq | NP_001191036.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
- Apoptosis - multiple species - Homo sapiens (human)
- FoxO signaling pathway - Homo sapiens (human)
- MicroRNAs in cancer - Homo sapiens (human)
Biological Process
- in utero embryonic development
- B cell homeostasis
- B cell apoptotic process
- kidney development
- protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
Molecular Function
- protein binding
- microtubule binding
- protein kinase binding
- protein heterodimerization activity
Cellular Component
- mitochondrion
- mitochondrial outer membrane
- cytosol
- endomembrane system
- extrinsic component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000393256
- Coding exons
- 3
- Length
- 49070
- Individuals with no LoFs
- 125582
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 125583
- p
- 0.00000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.121 | 115 | 119 | 0.969 | 0.00000692 | 1288 |
| Missense (PolyPhen) | 61 | 63.824 | 0.95575 | 701 | ||
| Synonymous | -0.900 | 51 | 43.5 | 1.17 | 0.00000258 | 397 |
| Loss of Function | 2.47 | 0 | 7.13 | 0.00 | 4.35e-7 | 71 |
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) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase-mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis. {ECO:0000269|PubMed:11997495, ECO:0000269|PubMed:15486195, ECO:0000269|PubMed:9430630}.;
Recessive Scores
- pRec
- 0.482
Intolerance Scores
- LoFtool
- 0.186
- RVIS EVS
- -0.25
- RVIS percentile EVS
- 35.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |