CHD1

Chr 5AD

chromodomain helicase DNA binding protein 1

Also known as: CHD-1, PILBOS

NCBI Gene: 1105ENSG00000153922UniProt: O14646

The CHD family of proteins is characterized by the presence of chromo (chromatin organization modifier) domains and SNF2-related helicase/ATPase domains. CHD genes alter gene expression possibly by modification of chromatin structure thus altering access of the transcriptional apparatus to its chromosomal DNA template. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Pilarowski-Bjornsson syndromeMIM #617682
AD
454
ClinVar variants
29
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CHD1
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADLimited

Limited evidence — not for standalone diagnostic reporting

⚡
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
29 Pathogenic / Likely Pathogenic· 354 VUS of 454 total submissions

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.
0.16LOEUF
pLI 1.000
Z-score 8.28
OE 0.09 (0.06–0.16)
Highly constrained

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

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.
4.21Z-score
OE missense 0.59 (0.55–0.64)
507 obs / 852.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

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 (0.06–0.16)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.59 (0.55–0.64)
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.0.96
0≤1.21.6
LoF obs/exp: 9 / 96.9Missense obs/exp: 507 / 852.9Syn Z: 0.53

ClinVar Variant Classifications

454 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic8
VUS354
Likely Benign50
Benign10
Conflicting11
21
Pathogenic
8
Likely Pathogenic
354
VUS
50
Likely Benign
10
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
18
0
21
Likely Pathogenic
3
2
3
0
8
VUS
22
287
43
2
354
Likely Benign
0
13
4
33
50
Benign
0
5
3
2
10
Conflicting
—11
Total263097137454

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

View in ClinVar →

Protein Context — Lollipop Plot

CHD1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CHD1-related neurodevelopment disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Pilarowski-Bjornsson syndrome

MIM #617682

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Discovery of common and rare genetic risk variants for colorectal cancer.
Huyghe JR et al.·Nat Genet
2019Meta-analysis
A genomic and epigenomic atlas of prostate cancer in Asian populations.
Li J et al.·Nature
2020
Prostate cancer.
Attard G et al.·Lancet
2016Review
Molecular Subtypes of Prostate Cancer.
Arora K et al.·Curr Oncol Rep
2018Review
Chd1 remodelers maintain open chromatin and regulate the epigenetics of differentiation.
Persson J et al.·Exp Cell Res
2010Review
Ductal, intraductal, and cribriform carcinoma of the prostate: Molecular characteristics and clinical management.
Shi Y et al.·Urol Oncol
2024Review
SPOP-Mutated/CHD1-Deleted Lethal Prostate Cancer and Abiraterone Sensitivity.
Boysen G et al.·Clin Cancer Res
2018
Folate intake and colorectal cancer risk according to genetic subtypes defined by targeted tumor sequencing.
Aglago EK et al.·Am J Clin Nutr
2024
CHD1 and SPOP synergistically protect prostate epithelial cells from DNA damage.
Zhu Y et al.·Prostate
2021
SPOP and CHD1 alterations in prostate cancer: Relationship with PTEN loss, tumor grade, perineural infiltration, and PSA recurrence.
Hernández-Llodrà S et al.·Prostate
2021
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools