BCL9

Chr 1

BCL9 transcription coactivator

Also known as: LGS

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.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.38
Clinical SummaryBCL9
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.38LOEUF
pLI 0.496
Z-score 4.65
OE 0.22 (0.130.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.04Z-score
OE missense 1.00 (0.941.05)
837 obs / 839.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.22 (0.130.38)
00.351.4
Missense OE1.00 (0.941.05)
00.61.4
Synonymous OE1.15
01.21.6
LoF obs/exp: 9 / 41.2Missense obs/exp: 837 / 839.9Syn Z: -2.10
DN
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.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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