DCHS1

Chr 11ADAR

dachsous cadherin-related 1

NCBI Gene: 8642ENSG00000166341UniProt: Q96JQ0

Calcium-dependent cell-adhesion protein. Mediates functions in neuroprogenitor cell proliferation and differentiation. In the heart, has a critical role for proper morphogenesis of the mitral valve, acting in the regulation of cell migration involved in valve formation (PubMed:26258302)

Primary Disease Associations & Inheritance

Mitral valve prolapse 2MIM #607829
AD
Van Maldergem syndrome 1MIM #601390
AR
2650
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DCHS1
⚡
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.
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ClinVar Variants
2650 total variants — no pathogenic classifications of 2650 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.24LOEUF
pLI 1.000
Z-score 7.64
OE 0.16 (0.10–0.24)
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.
2.40Z-score
OE missense 0.85 (0.81–0.88)
1630 obs / 1926.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.16 (0.10–0.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.81–0.88)
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.0.93
0≤1.21.6
LoF obs/exp: 15 / 95.6Missense obs/exp: 1630 / 1926.5Syn Z: 1.50

ClinVar Variant Classifications

2650 submitted variants in ClinVar

ClinVar

Classification Summary

Protein Context — Lollipop Plot

DCHS1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

DCHS1-related periventricular neuronal heterotopia

definitive
ARLoss 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

Mitral valve prolapse 2

MIM #607829

Molecular basis of disorder known

Autosomal dominant

Van Maldergem syndrome 1

MIM #601390

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic background of mitral valve prolapse.
Guicciardi NA et al.·Rev Cardiovasc Med
2022Review
Dchs1-Fat4 regulation of osteogenic differentiation in mouse.
Crespo-Enriquez I et al.·Development
2019Functional
DCHS1 DNA copy number loss associated with pediatric urinary tract infection risk.
Qureshi AH et al.·Innate Immun
2020Clinical trial
Mutation in mitral valve prolapse susceptible gene DCHS1 causes familial mitral annular disjunction.
Zhou N et al.·J Med Genet
2024
Deleterious variants in DCHS1 are prevalent in sporadic cases of mitral valve prolapse.
Clemenceau A et al.·Mol Genet Genomic Med
2018Case report
Identification of sequence variants associated with severe microtia-astresia by targeted sequencing.
Wang P et al.·BMC Med Genomics
2019
Molecular characteristics of varicocele: integration of whole-exome and transcriptome sequencing.
Yang B et al.·Fertil Steril
2021
Mutations in genes encoding the cadherin receptor-ligand pair DCHS1 and FAT4 disrupt cerebral cortical development.
Cappello S et al.·Nat Genet
2013
Report of a rare case of congenital mitral valve prolapse with chronic kidney disease--reconsidered genotype-phenotypic correlations.
Sun L et al.·Mol Genet Genomic Med
2021Case report
Early-onset multivalvular disease caused by a missense variant in lamin A/C.
Janin A et al.·HGG Adv
2025Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Dynamic Expression and Functional Implications of the Cell Polarity Gene, Dchs1, During Cardiac Development.
Byerly K et al.·Cells
2025🔓 Open AccessFunctional
Fat4 intracellular domain controls internalization of Fat4/Dchs1 planar polarity membrane complexes.
Easa Y et al.·Biophys J
2025
Connexin 43 dephosphorylation mediates the Dchs1/YAP/TEAD signaling pathway to induce cardiac fibrosis.
Wang M et al.·Biochim Biophys Acta Mol Cell Res
2025
A high-calcium environment induced ectopic calcification of renal interstitial fibroblasts via TFPI-2-DCHS1-ALP/ENPP1 axis to participate in Randall's plaque formation.
Liu M et al.·Urolithiasis
2024
Dachsous cadherin related 1 (DCHS1) is a novel biomarker for immune infiltration and epithelial-mesenchymal transition in endometrial cancer via pan-cancer analysis.
Meijuan C et al.·J Ovarian Res
2024🔓 Open Access
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