CHD5

Chr 1AD

chromodomain helicase DNA binding protein 5

Also known as: CHD-5, PMNDS

NCBI Gene: 26038ENSG00000116254UniProt: O00258

This gene encodes a member of the chromodomain helicase DNA-binding protein family. Members of this family are characterized by a chromodomain, a helicase ATP-binding domain and an additional functional domain. This gene encodes a neuron-specific protein that may function in chromatin remodeling and gene transcription. This gene is a potential tumor suppressor gene that may play a role in the development of neuroblastoma. [provided by RefSeq, Feb 2012]

Primary Disease Associations & Inheritance

Parenti-Mignot neurodevelopmental syndromeMIM #619873
AD
0
Active trials
30
Pathogenic / LP
384
ClinVar variants
12
Pubs (1 yr)
5.3
Missense Z· constrained
0.16
LOEUF· LoF intolerant
Clinical Summary— CHD5
⚡
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
30 Pathogenic / Likely Pathogenic· 314 VUS of 384 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 8.44
OE 0.09 (0.05–0.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
5.32Z-score
OE missense 0.56 (0.53–0.60)
668 obs / 1182.5 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.09 (0.05–0.16)
0≤0.351.4
Missense OE0.56 (0.53–0.60)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 9 / 100.2Missense obs/exp: 668 / 1182.5Syn Z: -0.05
LOF
DN
0.4090th %ile
GOF
0.3887th %ile
LOF
0.65top 25%

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

LOFprediction above median · 1 literature citation · 23% of P/LP variants are LoF · LOEUF 0.16

Literature Evidence

LOFThompson et al. (2003) also noted that microdeletions in monosomy 1p36 syndrome would include the CHD5 gene, suggesting that haploinsufficiency of CHD5 may contribute to the neurologic and developmental problems seen in those patients.PMID:12592387

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

384 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic10
VUS314
Likely Benign30
Benign8
Conflicting2
20
Pathogenic
10
Likely Pathogenic
314
VUS
30
Likely Benign
8
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
18
0
20
Likely Pathogenic
5
3
2
0
10
VUS
2
292
18
2
314
Likely Benign
0
9
4
17
30
Benign
0
1
2
5
8
Conflicting
—2
Total93054424384

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

View in ClinVar →

CHD5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CHD5-related neurodevelopmental disorder with intellectual disability, speech delay and epilepsy

limited
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Missense and truncating variants in CHD5 in a dominant neurodevelopmental disorder with intellectual disability, behavioral disturbances, and epilepsy.
Parenti I et al.·Hum Genet
2021
Large-scale discovery of novel neurodevelopmental disorder-related genes through a unified analysis of single-nucleotide and copy number variants.
Hamanaka K et al.·Genome Med
2022
CHD5 gene variant predicts leptomeningeal metastasis after surgical resection of brain metastases of breast cancer.
Otani R et al.·J Neurooncol
2023
Influence of colorectal cancer tumor suppressor gene CHD5 methylation on its clinical and pathological characteristics.
Liu JB et al.·J Biol Regul Homeost Agents
2015
A rare CHD5 haplotype and its interactions with environmental factors predicting hepatocellular carcinoma risk.
Xiao Q et al.·BMC Cancer
2018
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients