BRWD3

Chr XXLR

bromodomain and WD repeat domain containing 3

Also known as: BRODL, DCAF20, MRX93, XLID93

The BRWD3 protein contains a bromodomain and WD repeats that function in chromatin modification and transcriptional regulation, and also controls cell morphology and cytoskeletal organization. Mutations cause X-linked intellectual developmental disorder with macrocephaly. This gene is extremely intolerant to loss-of-function variation and follows X-linked recessive inheritance.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.081 OMIM phenotype
Clinical SummaryBRWD3
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Gene-Disease Validity (ClinGen)
X-linked syndromic intellectual disability · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 7.83
OE 0.03 (0.010.08)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
4.27Z-score
OE missense 0.54 (0.490.59)
369 obs / 682.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.03 (0.010.08)
00.351.4
Missense OE0.54 (0.490.59)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 2 / 75.4Missense obs/exp: 369 / 682.9Syn Z: -0.90
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveBRWD3-related intellectual developmental disorderLOFXLR
DN
0.18100th %ile
GOF
0.2995th %ile
LOF
0.84top 5%

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

LOFprediction above median · LOEUF 0.08

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

BRWD3 · 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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