BRD9

Chr 5

bromodomain containing 9

Also known as: LAVS3040, PRO9856, SMARCI2

NCBI Gene: 65980ENSG00000028310UniProt: Q9H8M2

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.

ResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.52
Clinical Summary— BRD9
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
135 unique Pathogenic / Likely Pathogenic· 113 VUS of 298 total submissions
Explore recent and relevant literature in Research Assistant →
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE0.30 (0.18–0.52)
0≤0.351.4
Missense OE0.81 (0.73–0.89)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 9 / 30.1Missense obs/exp: 285 / 351.7Syn Z: -0.45
DN
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

298 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic133
Likely Pathogenic2
VUS113
Likely Benign11
Benign7
133
Pathogenic
2
Likely Pathogenic
113
VUS
11
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
133
0
133
Likely Pathogenic
0
0
2
0
2
VUS
0
88
25
0
113
Likely Benign
0
7
3
1
11
Benign
0
0
6
1
7
Total0951692266

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

View in ClinVar →

Protein Context — Lollipop Plot

BRD9 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients