BCL2L2
protein-codingBCL2 like 2, the group of Protein phosphatase 1 regulatory subunits|BCL2 family
Gene summary
This gene encodes a member of the BCL-2 protein family. The proteins of this family form hetero- or homodimers and act as anti- and pro-apoptotic regulators. Expression of this gene in cells has been shown to contribute to reduced cell apoptosis under cytotoxic conditions. Studies of the related gene in mice indicated a role in the survival of NGF- and BDNF-dependent neurons. Mutation and knockout studies of the mouse gene demonstrated an essential role in adult spermatogenesis. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream PABPN1 (poly(A) binding protein, nuclear 1) gene. [provided by RefSeq, Dec 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.0 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 BCL2L2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004050.5. 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 | 0 | |||||
| missense | 11 | 11 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 11 | 0 | 0 | 11 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004041.2 | 2 | MANE Select | |
| Ensembl | ENSP00000250405.6 | 2 | MANE Select | |
| RefSeq | NP_001186768.2 | 2 | Standard | |
| Ensembl | ENSP00000451148.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- MicroRNAs in cancer - Homo sapiens (human)
- Apoptosis Modulation and Signaling
- Apoptosis
- Photodynamic therapy-induced NF-kB survival signaling
- Apoptotic Signaling Pathway
Biological Process
- spermatogenesis
- intrinsic apoptotic signaling pathway in response to DNA damage
- negative regulation of apoptotic process
- Sertoli cell proliferation
- extrinsic apoptotic signaling pathway in absence of ligand
Molecular Function
- protein binding
- identical protein binding
- protein homodimerization activity
- protein heterodimerization activity
- BH domain binding
Cellular Component
- mitochondrial outer membrane
- cytosol
- Bcl-2 family protein complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000250405
- Coding exons
- 2
- Length
- 12970
- Individuals with no LoFs
- 123857
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 123867
- p
- 0.0000404
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.05 | 75 | 105 | 0.712 | 0.00000671 | 1219 |
| Missense (PolyPhen) | 15 | 24.694 | 0.60744 | 306 | ||
| Synonymous | -0.230 | 45 | 43.1 | 1.04 | 0.00000251 | 435 |
| Loss of Function | 1.83 | 1 | 5.74 | 0.174 | 2.47e-7 | 66 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000063 | 0.000063 | rare |
| 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) | 0.000036 | 0.000036 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX. {ECO:0000269|PubMed:8761287}.;
Recessive Scores
- pRec
- 0.201
Intolerance Scores
- LoFtool
- 0.388
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.4
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.965
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |