BCL9

Chr 1

BCL9 transcription coactivator

Also known as: LGS

NCBI Gene: 607 ENSG00000116128 UniProt: O00512 OMIM: 602597

BCL9 encodes a protein that promotes beta-catenin transcriptional activity in Wnt signaling pathways and is highly constrained against loss-of-function variants (LOEUF 0.381). Mutations in BCL9 cause neurodevelopmental disorders with intellectual disability, though the specific phenotypic spectrum and inheritance patterns are detailed in GeneReviews. The gene's high constraint score suggests that heterozygous loss-of-function variants are likely pathogenic in the neurodevelopmental context.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.38

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.

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.04Z-score

OE missense 1.00 (0.94–1.05)

837 obs / 839.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.22 (0.13–0.38)

0≤0.351.4

Missense OE?1.00 (0.94–1.05)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 9 / 41.2Missense obs/exp: 837 / 839.9Syn Z: -2.10

This gene — mechanism propensity

0.3594th %ile

GOF

0.2298th %ile

LOF

0.78top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.38

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.