CHD7

Chr 8AD

chromodomain helicase DNA binding protein 7

Also known as: CRG, HH5, IS3, KAL5

NCBI Gene: 55636ENSG00000171316UniProt: Q9P2D1

This gene encodes a protein that contains several helicase family domains. Mutations in this gene have been found in some patients with the CHARGE syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

Primary Disease Associations & Inheritance

CHARGE syndromeMIM #214800
AD
Hypogonadotropic hypogonadism 5 with or without anosmiaMIM #612370
AD
UniProtIdiopathic scoliosis 3
499
ClinVar variants
59
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— CHD7
🧬
Gene-Disease Validity (ClinGen)
CHARGE syndrome · 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.
📋
ClinVar Variants
59 Pathogenic / Likely Pathogenic· 241 VUS of 499 total submissions
💊
Clinical Trials
1 active or recruiting trial — 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.
0.08LOEUF
pLI 1.000
Z-score 10.48
OE 0.04 (0.02–0.08)
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.
3.22Z-score
OE missense 0.77 (0.74–0.81)
1254 obs / 1618.5 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.0.04 (0.02–0.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.74–0.81)
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.1.04
0≤1.21.6
LoF obs/exp: 5 / 137.8Missense obs/exp: 1254 / 1618.5Syn Z: -0.81

ClinVar Variant Classifications

499 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic20
VUS241
Likely Benign160
Benign36
Conflicting3
39
Pathogenic
20
Likely Pathogenic
241
VUS
160
Likely Benign
36
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
2
17
0
39
Likely Pathogenic
9
6
5
0
20
VUS
1
220
18
2
241
Likely Benign
1
21
51
87
160
Benign
0
21
0
15
36
Conflicting
—3
Total3127091104499

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

View in ClinVar →

Protein Context — Lollipop Plot

CHD7 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CHD7-related CHARGE syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeEar
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

CHARGE syndrome

MIM #214800

Molecular basis of disorder known

Autosomal dominant

Hypogonadotropic hypogonadism 5 with or without anosmia

MIM #612370

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — CHD7
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CHARGE syndrome: a review.
Hsu P et al.·J Paediatr Child Health
2014Review
The Genomic and Epigenomic Landscape of Double-Negative Metastatic Prostate Cancer.
Lundberg A et al.·Cancer Res
2023
Clinical and molecular effects of CHD7 in the heart.
Corsten-Janssen N et al.·Am J Med Genet C Semin Med Genet
2017Review
CHARGE syndrome.
Blake KD et al.·Orphanet J Rare Dis
2006Review
CHD7 mutations and CHARGE syndrome: the clinical implications of an expanding phenotype.
Bergman JE et al.·J Med Genet
2011Review
[The CHARGE syndrome].
Klingenberg C et al.·Tidsskr Nor Laegeforen
2008Review
A novel cardiomyopathy phenotype linked to a CHD7 missense variant.
Park IY et al.·Sci Rep
2025
Mutation update on the CHD7 gene involved in CHARGE syndrome.
Janssen N et al.·Hum Mutat
2012Review
Congenital heart defects in CHARGE: The molecular role of CHD7 and effects on cardiac phenotype and clinical outcomes.
Meisner JK et al.·Am J Med Genet C Semin Med Genet
2020Review
Mutation spectrum of hearing loss patients in Northwest China: Identification of 20 novel variants.
Ma P et al.·Mol Genet Genomic Med
2024Cohort
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
Rare Fetal Genetic DiseasesCongenital Malformation

Characterization and Contribution of Genome-wide DNA Methylation (DNA Methylation Episignatures) in Rare Diseases With Prenatal Onset

NOT YET RECRUITING
NCT06475651Assistance Publique - Hôpitaux de ParisStarted 2024-06
Methylation analysis

External Resources

Links to major genomics databases and tools