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50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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BCL2
BCL2 apoptosis regulator
Chromosome 18 · 18q21.33
NCBI Gene: 596Ensembl: ENSG00000171791.14HGNC: HGNC:990UniProt: A0A7I2V3S7
2,225PubMed Papers
20Diseases
7Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
ApoptosisHub GeneOncogene
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of anoikisapoptotic processextrinsic apoptotic signaling pathway via death domain receptorsresponse to xenobiotic stimuluschronic lymphocytic leukemianeoplasmdiffuse large B-cell lymphomaneurodegenerative disease
✦AI Summary

BCL2 is a critical apoptosis regulator that suppresses programmed cell death across diverse cell types 12. It functions by controlling mitochondrial membrane permeability and inhibiting caspase activity through two mechanisms: preventing cytochrome c release from mitochondria and binding apoptosis-activating factor (APAF-1) 3. BCL2 also functions as an autophagy inhibitor by interacting with BECN1 and AMBRA1 during non-starvation conditions 456, and may attenuate inflammation by impairing NLRP1-inflammasome activation 7. Clinically, BCL2 deregulation is central to hematologic malignancies. BCL2 activation occurs through t(14;18) translocations in follicular lymphoma 8, and BCL2 overexpression defines poor-prognosis disease when concurrent with MYC deregulation in diffuse large B-cell lymphomas 9. Loss of microRNA-15/16, which normally target BCL2, further drives overexpression in chr18 lymphocytic leukemia 8. BCL2 inhibitors like venetoclax now represent standard frontline therapy for CLL, showing superior outcomes particularly in high-risk subgroups 10. BCL2 dysregulation also associates with autoimmune disease susceptibility 11 and suppresses apoptosis in solid tumors via Akt/mTOR signaling 12.

Sources cited
1
BCL2 suppresses apoptosis in lymphohematopoietic and neural cells
PMID: 1508712
2
BCL2 suppresses apoptosis in factor-dependent cell systems
PMID: 8183370
3
BCL2 regulates mitochondrial membrane permeability, inhibits caspases, prevents cytochrome c release, and binds APAF-1
PMID: 11368354
4
BCL2 inhibits autophagy by interacting with BECN1
PMID: 18570871
5
BCL2 inhibits autophagy by interacting with BECN1 and AMBRA1
PMID: 20889974
6
BCL2 inhibits autophagy function during non-starvation conditions
PMID: 21358617
7
BCL2 attenuates inflammation by impairing NLRP1-inflammasome activation
PMID: 17418785
8
BCL2 gene discovered in t(14;18) translocations in follicular lymphoma; miR-15/16 targets BCL2 as tumor suppressors; venetoclax developed for CLL treatment
PMID: 28984869
9
BCL2 deregulation with MYC defines double-hit/double-expressor lymphomas with poor outcomes in DLBCL
PMID: 30252929
10
BCL2 inhibitors represent standard frontline therapy for CLL with superior progression-free and overall survival versus chemotherapy
PMID: 39644006
11
BCL2 polymorphisms associated with rheumatoid arthritis susceptibility
PMID: 26905515
12
BCL2 suppresses apoptosis in colorectal cancer via Akt/mTOR signaling pathway
PMID: 37151875
Disease Associationsⓘ20
chronic lymphocytic leukemiaOpen Targets
0.74Strong
neoplasmOpen Targets
0.61Moderate
diffuse large B-cell lymphomaOpen Targets
0.57Moderate
neurodegenerative diseaseOpen Targets
0.54Moderate
prostate carcinomaOpen Targets
0.53Moderate
acute myeloid leukemiaOpen Targets
0.51Moderate
type 2 diabetes mellitusOpen Targets
0.50Moderate
multiple myelomaOpen Targets
0.50Moderate
lymphoid leukemiaOpen Targets
0.49Moderate
diabetes mellitusOpen Targets
0.46Moderate
lymphoid neoplasmOpen Targets
0.46Moderate
Abnormality of the skeletal systemOpen Targets
0.46Moderate
lymphomaOpen Targets
0.45Moderate
neoplasm of mature B-cellsOpen Targets
0.44Moderate
androgenetic alopeciaOpen Targets
0.44Moderate
non-Hodgkins lymphomaOpen Targets
0.42Moderate
sleep apneaOpen Targets
0.38Weak
adolescent idiopathic scoliosisOpen Targets
0.38Weak
esophageal adenocarcinomaOpen Targets
0.38Weak
bile duct carcinomaOpen Targets
0.37Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets7
APG-2575Phase III
Apoptosis regulator Bcl-2 inhibitor
chronic lymphocytic leukemia
NAVITOCLAXApproved
Apoptosis regulator Bcl-W inhibitor
neoplasm
OBATOCLAXPhase II
Apoptosis regulator Bcl-2 inhibitor
OBATOCLAX MESYLATEPhase III
Apoptosis regulator Bcl-2 inhibitor
small cell lung carcinoma
OBLIMERSENApproved
Bcl-2 mRNA antisense inhibitor
neoplasm
OBLIMERSEN SODIUMPhase III
Bcl-2 mRNA antisense inhibitor
cutaneous melanoma
VENETOCLAXApproved
Apoptosis regulator Bcl-2 inhibitor
chronic lymphocytic leukemia
Related Genes
VDAC1Protein interaction100%BECN2Protein interaction100%UVRAGProtein interaction100%AMBRA1Protein interaction100%TP53BP2Protein interaction100%BIKProtein interaction100%
Tissue Expression6 tissues
Ovary
100%
Brain
79%
Heart
54%
Bone Marrow
51%
Lung
30%
Liver
8%
Gene Interaction Network
Click a node to explore
BCL2VDAC1BECN2UVRAGAMBRA1TP53BP2BIK
PROTEIN STRUCTURE
Preparing viewer…
PDB8HTS · 1.25 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.37Moderately Constrained
pLIⓘ
0.99Intolerant
Observed/Expected LoF0.08 [0.03–0.37]
RankingsWhere BCL2 stands among ~20K protein-coding genes
  • #45of 20,598
    Most Researched2,225 · top 1%
  • #435of 1,025
    FDA-Approved Drug Targets3
  • #1,693of 17,882
    Most Constrained (LOEUF)0.37 · top 10%
Genes detectedBCL2
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Risk-stratification in frontline CLL therapy: standard of care.
PMID: 39644006
Hematology Am Soc Hematol Educ Program · 2024
1.00
2
Double hit and double expressors in lymphoma: Definition and treatment.
PMID: 30252929
Cancer · 2018
0.90
3
The evolving frontline management of CLL: are triplets better than doublets? How will we find out?
PMID: 39644005
Hematology Am Soc Hematol Educ Program · 2024
0.80
4
BCL2 and miR-15/16: from gene discovery to treatment.
PMID: 28984869
Cell Death Differ · 2018
0.80
5
PMID: 32912960
J Clin Pathol · 2021
0.78