CHD3

Chr 17AD

chromodomain helicase DNA binding protein 3

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

NCBI Gene: 1107 ENSG00000170004 UniProt: Q12873 OMIM: 602120

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a member of the CHD family of proteins which are characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. This protein is one of the components of a histone deacetylase complex referred to as the Mi-2/NuRD complex which participates in the remodeling of chromatin by deacetylating histones. Chromatin remodeling is essential for many processes including transcription. Autoantibodies against this protein are found in a subset of patients with dermatomyositis. Three alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.151 OMIM phenotype

Clinical Summary— CHD3

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Gene-Disease Validity (ClinGen)

Snijders Blok-Campeau syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.

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Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.15LOEUF

pLI 1.000

Z-score 9.10

OE 0.09 (0.05–0.15)

Highly constrained

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

Missense Constraint?

6.15Z-score

OE missense 0.50 (0.46–0.53)

591 obs / 1187.6 exp

Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios?

LoF OE?0.09 (0.05–0.15)

0≤0.351.4

Missense OE?0.50 (0.46–0.53)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

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

This gene — mechanism propensity

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.