BRD9

Chr 5

bromodomain containing 9

Also known as: LAVS3040, PRO9856, SMARCI2

NCBI Gene: 65980 ENSG00000028310 UniProt: Q9H8M2 OMIM: 618465

BRD9 encodes a chromatin reader protein that binds acetylated histones and is a component of the SWI/SNF chromatin remodeling complex, which regulates gene transcription and DNA repair through homologous recombination. Mutations cause Kleefstra syndrome II, an autosomal dominant neurodevelopmental disorder characterized by intellectual disability, developmental delay, and distinctive facial features. The gene is highly constrained against loss-of-function variants (LOEUF 0.52), reflecting its essential role in normal development.

OMIM ResearchSummary from RefSeq, UniProt

Enables lysine-acetylated histone binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of SWI/SNF complex. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.52

Clinical Summary— BRD9

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

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ClinVar Variants

88 VUS of 134 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.52LOEUF

pLI 0.015

Z-score 3.57

OE 0.30 (0.18–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.26Z-score

OE missense 0.81 (0.73–0.89)

285 obs / 351.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.30 (0.18–0.52)

0≤0.351.4

Missense OE?0.81 (0.73–0.89)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 9 / 30.1Missense obs/exp: 285 / 351.7Syn Z: -0.45

This gene — mechanism propensity

0.6357th %ile

GOF

0.5563th %ile

LOF

0.49top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

134 submitted variants in ClinVar

ClinVar

Classification Summary

VUS88

Likely Benign9

Benign5

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	88	0	0	88
Likely Benign	7	1	1	9
Benign	0	4	1	5
Total	95	5	2	102

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

View in ClinVar →

137 pathogenic / likely-pathogenic (of 167) ClinVar copy-number / structural variants overlap BRD9 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →