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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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BCL9L
BCL9 like
Chromosome 11 · 11q23.3
NCBI Gene: 283149Ensembl: ENSG00000186174.13HGNC: HGNC:23688UniProt: A0A087WZX0
52PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
nucleoplasmbeta-catenin bindingpositive regulation of epithelial to mesenchymal transitionregulation of cell morphogenesiscolorectal adenocarcinomacolon adenocarcinomagastric intestinal type adenocarcinomaEndometrial Endometrioid Adenocarcinoma
✦AI Summary

BCL9L is a transcriptional coactivator that promotes β-catenin-dependent gene expression and plays a critical role in Wnt/β-catenin signaling 1. The protein contains conserved domains (B9H1-B9H6) that enable binding to β-catenin and interaction with transcriptional machinery, with B9H1 and B9H2 domains functioning as binding regions for Pygo and β-catenin respectively 23. BCL9L mRNA is expressed in multiple tissues including fetal brain, lung, and several tumor types 2. In cancer biology, BCL9L serves as an oncogenic cofactor whose expression is elevated in bladder cancer and associated with tumor progression 45. BCL9L knockdown significantly suppresses cancer cell proliferation, migration, and invasion in bladder cancer models 4. At the mechanistic level, NAT10-mediated acetylation modification regulates BCL9L mRNA stability and translation efficiency in bladder cancer cells 5. Beyond cancer cell-intrinsic effects, BCL9L modulates tumor immunity: targeting BCL9/BCL9L enhances antigen presentation by promoting conventional type 1 dendritic cell activation and infiltration 6, while β-catenin-BCL9/BCL9L signaling suppresses expression of butyrophilin-like molecules, enabling immune evasion from γδ T-cell immunosurveillance in colon cancer 7. These findings position BCL9L as a potential therapeutic target for cancer treatment and immunotherapy.

Sources cited
1
BCL9L is an epigenetic/transcriptional regulator that interacts with β-catenin/CTNNB1 and functions in Wnt signaling; gain-of-function CTNNB1 mutations are detected across multiple cancer types
PMID: 29786110
2
Human BCL9L gene consists of eight exons; BCL9L protein contains conserved B9H1-B9H6 domains with B9H1 and B9H2 corresponding to binding regions; BCL9L mRNA is expressed in fetal brain, lung, and multiple tumor types including pancreatic and prostate cancer
PMID: 12964048
3
Rat Bcl9l encodes a nuclear scaffold protein functioning as positive regulator for Wnt-β-catenin pathway; B9H1/B9H2 domains function as binding regions for Pygo and Arm (β-catenin)
PMID: 15703843
4
BCL9L is elevated in bladder cancer tissues; BCL9L knockdown and Wnt/β-catenin inhibition significantly repress proliferation, migration and invasion of bladder cancer cells
PMID: 35628130
5
NAT10-mediated ac4C mRNA modification regulates BCL9L stability and translation efficiency in bladder cancer; BCL9L is a target gene for NAT10-dependent acetylation
PMID: 35522942
6
Targeting BCL9/BCL9L enhances antigen presentation by promoting conventional type 1 dendritic cell activation and tumor infiltration; BCL9/BCL9L inhibition boosts antitumor CD8+ T cell responses
PMID: 38811552
7
β-catenin activation through BCL9/BCL9L suppresses butyrophilin-like (BTNL) gene expression; deletion of Bcl9/Bcl9l restores BTNL expression and γδ T-cell infiltration in colon cancer models
PMID: 37309673
Disease Associationsⓘ20
colorectal adenocarcinomaOpen Targets
0.57Moderate
colon adenocarcinomaOpen Targets
0.40Moderate
cecum adenocarcinomaOpen Targets
0.37Weak
cutaneous melanomaOpen Targets
0.37Weak
Endometrial Endometrioid AdenocarcinomaOpen Targets
0.37Weak
gastric carcinomaOpen Targets
0.37Weak
gastric intestinal type adenocarcinomaOpen Targets
0.37Weak
lymphoid neoplasmOpen Targets
0.37Weak
nodular melanomaOpen Targets
0.37Weak
skin basal cell carcinomaOpen Targets
0.37Weak
skin squamous cell carcinomaOpen Targets
0.37Weak
superficial spreading melanomaOpen Targets
0.37Weak
hepatocellular carcinomaOpen Targets
0.30Weak
urinary bladder carcinomaOpen Targets
0.30Weak
lung adenocarcinomaOpen Targets
0.29Weak
melanomaOpen Targets
0.28Weak
bladder transitional cell carcinomaOpen Targets
0.28Weak
chronic lymphocytic leukemiaOpen Targets
0.28Weak
non-small cell lung carcinomaOpen Targets
0.28Weak
oral squamous cell carcinomaOpen Targets
0.28Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CTNNB1Protein interaction100%HNF4AProtein interaction96%TCF4Protein interaction96%TLE1Protein interaction96%TLE3Protein interaction96%TLE4Protein interaction96%
Tissue Expression6 tissues
Ovary
100%
Lung
95%
Heart
59%
Bone Marrow
39%
Liver
35%
Brain
25%
Gene Interaction Network
Click a node to explore
BCL9LCTNNB1HNF4ATCF4TLE1TLE3TLE4
PROTEIN STRUCTURE
Preparing viewer…
PDB4UP0 · 1.28 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.30Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.20 [0.14–0.30]
RankingsWhere BCL9L stands among ~20K protein-coding genes
  • #8,532of 20,598
    Most Researched52
  • #1,146of 17,882
    Most Constrained (LOEUF)0.30 · top 10%
Genes detectedBCL9L
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Multi‑layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β‑catenin signaling activation (Review).
PMID: 29786110
Int J Mol Med · 2018
1.00
2
Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors.
PMID: 35685361
Comput Struct Biotechnol J · 2022
0.90
3
Identification and characterization of human BCL9L gene and mouse Bcl9l gene in silico.
PMID: 12964048
Int J Mol Med · 2003
0.80
4
NAT10-mediated mRNA N4-acetylcytidine modification promotes bladder cancer progression.
PMID: 35522942
Clin Transl Med · 2022
0.70
5
Identification and characterization of rat Bcl9l gene in silico.
PMID: 15703843
Int J Oncol · 2005
0.60