BCL2
Chr 18BCL2 apoptosis regulator
Also known as: Bcl-2, PPP1R50
The BCL2 protein is an integral outer mitochondrial membrane protein that suppresses apoptosis by regulating mitochondrial membrane permeability and inhibiting caspase activity, and also functions as an inhibitor of autophagy. Germline mutations cause autosomal dominant immunodeficiency with polyclonal lymphoproliferation, typically presenting in childhood with recurrent infections, lymphadenopathy, and splenomegaly. The gene shows moderate tolerance to loss-of-function variants (LOEUF 0.71), and while BCL2 translocations are well-known in follicular lymphoma, the germline mutations cause a distinct primary immunodeficiency phenotype.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is gain-of-function.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
124 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | — | — | — | — | 87 |
Likely Pathogenic | — | — | — | — | 7 |
VUS | — | — | — | — | 13 |
Likely Benign | — | — | — | — | 1 |
Benign | — | — | — | — | 2 |
| Total | — | 110 | |||
Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
BCL2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Testing Oral Decitabine and Cedazuridine (ASTX727) in Combination With Venetoclax for Higher-Risk Acute Myeloid Leukemia Patients
ACTIVE NOT RECRUITINGSepantronium Bromide for the Treatment of High-grade B-cell Lymphoma
ACTIVE NOT RECRUITINGEffect of Exercise Type on Muscle Quality in Patients With OA, SARC and RA: an Explorative Study
NOT YET RECRUITINGAn AAV Gene Therapy Trial of AFTX-201 in Adults With BAG3-Associated Dilated Cardiomyopathy (DCM)
NOT YET RECRUITINGVenetoclax Plus R-ICE Chemotherapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma
ACTIVE NOT RECRUITINGVenetoclax Resistance Landscape in Chronic Lymphocytic Leukemia
RECRUITINGObservatory of Prolymphocytic Leukemia T
RECRUITINGNavitoclax in Relapsed or Refractory High-Risk Myelodysplastic Syndrome
ACTIVE NOT RECRUITINGUnravelling the Role of Apoptosis in Platelets Biogenesis Through the Study of the Thrombocytopenia THC4
ACTIVE NOT RECRUITINGPersonalized NK Cell Therapy in CBT
RECRUITINGSingle Cell Acute Leukemia Analysis
NOT YET RECRUITINGFecal Microbiome Transplant to Remodel Intestinal Microbiota for Patients With Relapsed or Refractory Lymphoma With Exposure to High-Risk Antibiotics Who Are Receiving Chimeric Antigen Receptor T Cells
RECRUITINGExternal Resources
Links to major genomics databases and tools