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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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BCL2L2
BCL2 like 2
Chromosome 14 · 14q11.2
NCBI Gene: 599Ensembl: ENSG00000129473.12HGNC: HGNC:42959UniProt: Q92843
130PubMed Papers
20Diseases
3Drugs
0Pathogenic Variants
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
disordered domain specific bindingregulation of apoptotic processprotein bindingnegative regulation of apoptotic processneurodegenerative diseaseoculopharyngeal muscular dystrophy 1oculopharyngeal muscular dystrophyneoplasm
✦AI Summary

BCL2L2 (BCL2 like 2) is an anti-apoptotic protein that promotes cell survival through suppression of pro-apoptotic pathways. The protein contains four BCL-2 homology domains 1 and functions as a key regulator of the intrinsic apoptotic pathway, blocking mitochondrial outer membrane permeabilization and cytochrome c release 2. BCL2L2 exerts its pro-survival effects by restraining BAX activity 3 and is particularly important in regulating cell survival during development and differentiation. In cancer biology, BCL2L2 promotes tumorigenesis through multiple mechanisms. miR-29b and miR-16 suppress BCL2L2 expression to inhibit glioblastoma and oral squamous cell carcinoma progression respectively, demonstrating BCL2L2's role in cancer cell survival and stemness maintenance 45. A glioblastoma-associated Bcl2l2-Pabpn1 fusion transcript promotes tumor progression by blocking Bax activity and activating PI3K/AKT signaling 3. In megakaryocyte biology, BCL2L2 overexpression decreases apoptosis, increases proplatelet formation by 58%, and is positively associated with platelet number in healthy donors 6. BCL2L2 gene expression is regulated through alternative splicing mechanisms involving 5' UTR elements and upstream open reading frames 1, with splice isoform-specific targeting representing a potential therapeutic approach in cancer 7. Additionally, the miR-140/BCL2L2 axis regulates smooth muscle cell apoptosis in intracranial aneurysm formation 8.

Sources cited
1
BCL2L2 encodes a 193 amino acid protein with four BCL-2 homology domains; expression is regulated through alternative splicing and upstream open reading frames in the 5' UTR
PMID: 36272652
2
miR-29b directly targets BCL2L2's 3'UTR to downregulate its expression and inhibit glioblastoma tumorigenicity, migration, invasion, and stemness maintenance
PMID: 26155940
3
miR-16 directly targets BCL2L2; BCL2L2 downregulation inhibits oral squamous cell carcinoma cell proliferation and induces apoptosis
PMID: 30136280
4
Bcl2l2-Pabpn1 fusion transcript in glioblastoma blocks Bax activity and activates PI3K/AKT pathway to promote tumor progression
PMID: 35894779
5
BCL2L2 is a target of BH3 mimetic drugs like navitoclax; BCL-XL and BCL2L2 are critical pro-survival proteins in platelet apoptotic regulation
PMID: 24467740
6
BCL2L2 alternative splicing is implicated in prostate cancer; splice isoforms may have antagonistic functions
PMID: 29693622
7
miR-140 directly targets BCL2L2; the miR-140/BCL2L2 axis regulates smooth muscle cell apoptosis in intracranial aneurysm progression
PMID: 36441929
8
BCL2L2 overexpression restrains megakaryocyte apoptosis, increases proplatelet formation by 58%, and is positively correlated with platelet number in healthy donors
PMID: 30733267
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.55Moderate
oculopharyngeal muscular dystrophy 1Open Targets
0.48Moderate
oculopharyngeal muscular dystrophyOpen Targets
0.44Moderate
neoplasmOpen Targets
0.41Moderate
primary myelofibrosisOpen Targets
0.33Weak
small cell lung carcinomaOpen Targets
0.28Weak
myelofibrosisOpen Targets
0.28Weak
chronic lymphocytic leukemiaOpen Targets
0.11Weak
azoospermiaOpen Targets
0.09Suggestive
glioblastoma multiformeOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
partial chromosome Y deletionOpen Targets
0.08Suggestive
cancerOpen Targets
0.08Suggestive
spermatogenic failure 71Open Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
lymphomaOpen Targets
0.08Suggestive
spermatogenic failure 25Open Targets
0.08Suggestive
spermatogenic failure 57Open Targets
0.08Suggestive
spermatogenic failure 50Open Targets
0.08Suggestive
ovarian cancerOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets3
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
Related Genes
BAK1Protein interaction99%BAXProtein interaction99%BIKProtein interaction99%BECN1Protein interaction99%HRKProtein interaction97%BMFProtein interaction95%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
55%
Lung
35%
Ovary
33%
Brain
30%
Heart
7%
Gene Interaction Network
Click a node to explore
BCL2L2BAK1BAXBIKBECN1HRKBMF
PROTEIN STRUCTURE
Preparing viewer…
PDB4CIM · 1.50 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.88LoF Tolerant
pLIⓘ
0.20Tolerant
Observed/Expected LoF0.45 [0.24–0.88]
RankingsWhere BCL2L2 stands among ~20K protein-coding genes
  • #3,582of 20,598
    Most Researched130 · top quartile
  • #920of 1,025
    FDA-Approved Drug Targets1
  • #7,862of 17,882
    Most Constrained (LOEUF)0.88
Genes detectedBCL2L2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Sequence and expression regulation of the BCL2L2 gene in pigs.
PMID: 36272652
Gene · 2023
1.00
2
miR-29b attenuates tumorigenicity and stemness maintenance in human glioblastoma multiforme by directly targeting BCL2L2.
PMID: 26155940
Oncotarget · 2015
0.90
3
MicroRNA-16 functions as a tumor-suppressor gene in oral squamous cell carcinoma by targeting AKT3 and BCL2L2.
PMID: 30136280
J Cell Physiol · 2018
0.80
4
Novel read-through fusion transcript Bcl2l2-Pabpn1 in glioblastoma cells.
PMID: 35894779
J Cell Mol Med · 2022
0.70
5
The role of apoptosis in megakaryocytes and platelets.
PMID: 24467740
Br J Haematol · 2014
0.60