BCL9

Chr 1

BCL9 transcription coactivator

Also known as: LGS

NCBI Gene: 607ENSG00000116128UniProt: O00512

BCL9 is associated with B-cell acute lymphoblastic leukemia. It may be a target of translocation in B-cell malignancies with abnormalities of 1q21. Its function is unknown. The overexpression of BCL9 may be of pathogenic significance in B-cell malignancies. [provided by RefSeq, Jul 2008]

536
ClinVar variants
286
Pathogenic / LP
0.50
pLI score
0
Active trials
Clinical Summary— BCL9
🧬
Gene-Disease Validity (ClinGen)
congenital heart disease · ADLimited

Limited evidence — not for standalone diagnostic reporting

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
286 Pathogenic / Likely Pathogenic· 233 VUS of 536 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.38LOEUF
pLI 0.496
Z-score 4.65
OE 0.22 (0.13–0.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.04Z-score
OE missense 1.00 (0.94–1.05)
837 obs / 839.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.22 (0.13–0.38)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.94–1.05)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.15
0≤1.21.6
LoF obs/exp: 9 / 41.2Missense obs/exp: 837 / 839.9Syn Z: -2.10

ClinVar Variant Classifications

536 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic248
Likely Pathogenic38
VUS233
Likely Benign11
Benign3
Conflicting3
248
Pathogenic
38
Likely Pathogenic
233
VUS
11
Likely Benign
3
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
248
0
248
Likely Pathogenic
0
0
38
0
38
VUS
0
223
10
0
233
Likely Benign
0
4
2
5
11
Benign
0
2
0
1
3
Conflicting
—3
Total02292986536

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

BCL9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — BCL9
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Targeting tumor-intrinsic BCL9 reverses immunotherapy resistance by eliciting macrophage-mediated phagocytosis and antigen presentation.
Wu SY et al.·Nat Commun
2025
Prognostic and survival impact of BCL9 and RPS6KB1 copy number variation detected from circulating free DNA in hepatocellular carcinoma.
Youssef SS et al.·Expert Rev Mol Diagn
2023
BCL9 and C9orf5 are associated with negative symptoms in schizophrenia: meta-analysis of two genome-wide association studies.
Xu C et al.·PLoS One
2013Meta-analysis
Genetic and clinical characteristics of acute B-cell lymphoblastic leukemia with MEF2D fusions and report of two novel MEF2D rearrangements.
Cao HY et al.·Ann Hematol
2024
Genetic Predisposition to Schizophrenia and Depressive Disorder Comorbidity.
Shnayder NA et al.·Genes (Basel)
2022Review
Dysregulated BCL9 Controls Tumorigenicity and Ferroptosis Susceptibility by Binding With Nrf2 in Thyroid Carcinoma.
Wang B et al.·Mol Carcinog
2024
[Clinical characteristics and outcomes of childhood B-ALL with ZNF384 and MEF2D rearrangements].
Hirabayashi S et al.·Rinsho Ketsueki
2023
Clinical and molecular characteristics of paediatric mature B-cell acute lymphocytic leukaemia and non-Hodgkin lymphoma with bone marrow involvement: A joint study between the CCCG leukaemia and lymphoma groups.
Zhao J et al.·Br J Haematol
2025
MicroRNA-1301 inhibits migration and invasion of osteosarcoma cells by targeting BCL9.
Wang L et al.·Gene
2018
LncRNA MNX1-AS1 Contributes to Laryngeal Squamous Cell Carcinoma Growth and Migration by Regulating mir-744-5p/bcl9/β-Catenin Axis.
Ma B et al.·Cell Transplant
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools