CHD3

Chr 17AD

chromodomain helicase DNA binding protein 3

Also known as: Mi-2a, Mi2-ALPHA, SNIBCPS, ZFH

This protein functions as a component of the Mi-2/NuRD complex, which remodels chromatin by deacetylating histones and is essential for transcriptional regulation. Loss-of-function mutations cause Snijders Blok-Campeau syndrome through an autosomal dominant inheritance pattern. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the pathogenic mechanism.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.151 OMIM phenotype
Clinical SummaryCHD3
🧬
Gene-Disease Validity (ClinGen)
Snijders Blok-Campeau syndrome · ADDefinitive

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.
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.15LOEUF
pLI 1.000
Z-score 9.10
OE 0.09 (0.050.15)
Highly constrained

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

Missense Constraint
6.15Z-score
OE missense 0.50 (0.460.53)
591 obs / 1187.6 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.09 (0.050.15)
00.351.4
Missense OE0.50 (0.460.53)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 10 / 115.5Missense obs/exp: 591 / 1187.6Syn Z: 0.04
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCHD3-related macrocephaly and impaired speech and languageOTHERAD
DN
0.3991th %ile
GOF
0.4085th %ile
LOF
0.68top 25%

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

LOFprediction above median · LOEUF 0.15

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

CHD3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →