CHD2

Chr 15AD

chromodomain helicase DNA binding protein 2

Also known as: DEE94, EEOC

CHD2 encodes a chromatin remodeling protein that uses its helicase/ATPase domains to modify chromatin structure and regulate gene expression. Mutations cause developmental and epileptic encephalopathy 94, inherited in an autosomal dominant pattern. The gene is highly intolerant to loss-of-function variants, and mutations predominantly cause disease through haploinsufficiency.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.071 OMIM phenotype
Clinical SummaryCHD2
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · 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.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.07LOEUF
pLI 1.000
Z-score 9.50
OE 0.03 (0.010.07)
Highly constrained

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

Missense Constraint
5.21Z-score
OE missense 0.53 (0.490.57)
523 obs / 982.0 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.03 (0.010.07)
00.351.4
Missense OE0.53 (0.490.57)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 3 / 111.0Missense obs/exp: 523 / 982.0Syn Z: 0.71
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCHD2-related epileptic encephalopathyLOFAD
DN
0.4289th %ile
GOF
0.2995th %ile
LOF
0.72top 10%

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

LOFprediction above median · 1 literature citation · LOEUF 0.07

Literature Evidence

LOFThe results of this study, in addition to our review of the literature, support a causative role of CHD2 haploinsufficiency in developmental delay, intellectual disability, epilepsy and behavioural problems, with phenotypic variability between individuals.PMID:24834135

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

CHD2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗