CHD3

Chr 17AD

chromodomain helicase DNA binding protein 3

NCBI Gene: 1107ENSG00000170004UniProt: Q12873

ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA (PubMed:28977666). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666, PubMed:30397230, PubMed:9804427). Involved in transcriptional repression as part of the NuRD complex (PubMed:27068747). Required for anchoring centrosomal pericentrin in both interphase and mitosis, for spindle organization and centrosome integrity (PubMed:17626165)

Primary Disease Associations & Inheritance

Snijders Blok-Campeau syndromeMIM #618205
AD
856
ClinVar variants
81
Pathogenic / LP
1.00
pLI score· haploinsufficient
2
Active trials
Clinical Summary— CHD3
⚡
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.
📋
ClinVar Variants
81 Pathogenic / Likely Pathogenic· 401 VUS of 856 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.09 (0.05–0.15)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.50 (0.46–0.53)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 10 / 115.5Missense obs/exp: 591 / 1187.6Syn Z: 0.04

ClinVar Variant Classifications

856 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic45
VUS401
Likely Benign68
Benign3
Conflicting16
36
Pathogenic
45
Likely Pathogenic
401
VUS
68
Likely Benign
3
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
6
16
0
36
Likely Pathogenic
11
26
7
1
45
VUS
6
370
22
3
401
Likely Benign
0
39
10
19
68
Benign
0
0
2
1
3
Conflicting
—16
Total314415724569

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

View 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.

Gene2Phenotype Curations

CHD3-related macrocephaly and impaired speech and language

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Snijders Blok-Campeau syndrome

MIM #618205

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Inherited variants in CHD3 show variable expressivity in Snijders Blok-Campeau syndrome.
van der Spek J et al.·Genet Med
2022
Snijders Blok-Campeau Syndrome: Description of 20 Additional Individuals with Variants in CHD3 and Literature Review.
Pascual P et al.·Genes (Basel)
2023Review
CHD3 helicase domain mutations cause a neurodevelopmental syndrome with macrocephaly and impaired speech and language.
Snijders Blok L et al.·Nat Commun
2018
The NuRD component CHD3 promotes BMP signalling during cranial neural crest cell specification.
Mitchell ZH et al.·EMBO Rep
2025
The NuRD complex and macrocephaly associated neurodevelopmental disorders.
Pierson TM et al.·Am J Med Genet C Semin Med Genet
2019Review
Utility of genome sequencing in exome-negative pediatric patients with neurodevelopmental phenotypes.
Nomakuchi TT et al.·Am J Med Genet A
2024Cohort
A severe neurocognitive phenotype caused by biallelic CHD3 variants in two siblings.
Goldfarb Yaacobi R et al.·Am J Med Genet A
2024
CHD3-related Snijders Blok-Campeau syndrome with Spastic Paraplegia, Ataxia, and Situs Inversus.
Chen L et al.·Eur J Med Genet
2025Case report
A novel CHD3 variant in a patient with central precocious puberty: Expanded phenotype of Snijders Blok-Campeau syndrome?
LeBreton L et al.·Am J Med Genet A
2023Case report
A de novo CHD3 variant in a child with intellectual disability, autism, joint laxity, and dysmorphisms.
Mizukami M et al.·Brain Dev
2021Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Developmental Delay DisorderIntellectual DisabilityRare Diseases

Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation

RECRUITING
NCT06860672Phase EARLY_PHASE1Yongguo YuStarted 2025-02-19
Dual vector DNA base editor
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools