CHD5

Chr 1AD

chromodomain helicase DNA binding protein 5

Also known as: CHD-5, PMNDS

NCBI Gene: 26038ENSG00000116254UniProt: O00258OMIM: 610771

The protein is a neuron-specific chromodomain helicase that functions in chromatin remodeling and gene transcription. Mutations cause Parenti-Mignot neurodevelopmental syndrome with autosomal dominant inheritance. CHD5 is highly constrained against loss-of-function variants (pLI ~1.0), indicating that even single functional copies are critical for normal neurodevelopment.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.161 OMIM phenotype
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
56 unique Pathogenic / Likely Pathogenic· 393 VUS of 520 total submissions
Explore recent and relevant literature in Research Assistant →

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
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCHD5-related neurodevelopmental disorder with intellectual disability, speech delay and epilepsyLOFAD
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 · 27% 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

520 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic16
VUS393
Likely Benign44
Benign8
Conflicting3
40
Pathogenic
16
Likely Pathogenic
393
VUS
44
Likely Benign
8
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
32
0
40
Likely Pathogenic
7
9
0
0
16
VUS
3
367
21
2
393
Likely Benign
0
11
6
27
44
Benign
0
1
2
5
8
Conflicting
—3
Total183886134504

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

View in ClinVar →

Protein Context — Lollipop Plot

CHD5 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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
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
CHD5 gene variant predicts leptomeningeal metastasis after surgical resection of brain metastases of breast cancer.
Otani R et al.·J Neurooncol
2023
[Methylation of CHD5 Gene Promoter Regulates p19(Arf)/p53/p21(Cip1) Pathway to Facilitate Pathogenesis of Acute Myeloid Leukemia].
Wu MC et al.·Zhongguo Shi Yan Xue Ye Xue Za Zhi
2019
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