BRD3

Chr 9

bromodomain containing 3

Also known as: FSHRG2, ORFX, RING3L

BRD3 encodes a chromatin reader protein that recognizes and binds acetylated histones to control gene expression and recruit transcriptional machinery. Mutations cause autosomal dominant developmental delay with intellectual disability, seizures, and dysmorphic features, typically presenting in early childhood. This gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.32
Clinical SummaryBRD3
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 76 VUS of 151 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.32LOEUF
pLI 0.975
Z-score 4.30
OE 0.14 (0.070.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.64Z-score
OE missense 0.65 (0.590.72)
302 obs / 461.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.14 (0.070.32)
00.351.4
Missense OE0.65 (0.590.72)
00.61.4
Synonymous OE1.10
01.21.6
LoF obs/exp: 4 / 28.9Missense obs/exp: 302 / 461.3Syn Z: -1.16
DN
0.3991th %ile
GOF
0.3292th %ile
LOF
0.73top 10%

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

LOFprediction above median · LOEUF 0.32

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

151 submitted variants in ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic1
VUS76
Likely Benign8
Benign3
38
Pathogenic
1
Likely Pathogenic
76
VUS
8
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
38
0
38
Likely Pathogenic
0
0
1
0
1
VUS
1
68
7
0
76
Likely Benign
0
6
2
0
8
Benign
0
0
1
2
3
Total174492126

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

View in ClinVar →

Protein Context — Lollipop Plot

BRD3 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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