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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
DCHS1
dachsous cadherin-related 1
Chromosome 11 Β· 11p15.4
NCBI Gene: 8642Ensembl: ENSG00000166341.9HGNC: HGNC:13681UniProt: Q96JQ0
26PubMed Papers
22Diseases
0Drugs
40Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
cell migration involved in endocardial cushion formationmitral valve formationhippo signalingcell-cell adhesionvan Maldergem syndrome 1mitral valve prolapseCerebro-facio-articular syndromemitral valve prolapse, myxomatous 2
✦AI Summary

DCHS1 encodes a calcium-dependent cell adhesion protein that plays critical roles in development and tissue organization. The protein functions as an atypical cadherin that forms heterophilic interactions with FAT4, creating high-affinity binding interfaces essential for planar cell polarity signaling 1. DCHS1 regulates cell proliferation and differentiation through multiple pathways, including modulation of Hippo signaling via YAP-TEAD activity during osteoblast differentiation 2. In cardiac development, DCHS1 is essential for proper mitral valve morphogenesis, where it interacts with the septin-actin cytoskeleton through LIX1L to direct cell-ECM alignment and valve tissue formation 3. The protein also influences brain development, with modern human-specific glycosylation changes affecting neocortex-to-striatum proportions through modulation of EPHA4-ephrin signaling 4. Disease-associated mutations in DCHS1 cause periventricular heterotopia with neuronal hyperactivity due to altered sodium channel function and increased morphological complexity 5. Clinically, DCHS1 mutations are associated with Van Maldergem syndrome, mitral valve prolapse, and genetic generalized epilepsy, highlighting its importance across multiple developmental processes 67.

Sources cited
1
DCHS1 forms high-affinity heterophilic interactions with FAT4 for planar cell polarity
PMID: 36797229
2
DCHS1 regulates osteoblast differentiation through Hippo signaling and YAP-TEAD activity
PMID: 31358536
3
DCHS1 is essential for mitral valve morphogenesis through septin-actin cytoskeleton interactions
PMID: 35200715
4
Modern human-specific DCHS1 glycosylation changes affect brain proportions via EPHA4-ephrin signaling
PMID: 40463223
5
DCHS1 mutations cause periventricular heterotopia with neuronal hyperactivity
PMID: 39966398
6
DCHS1 mutations are associated with mitral valve prolapse
PMID: 35345263
7
DCHS1 variants are linked to genetic generalized epilepsy
PMID: 39574152
Disease Associationsβ“˜22
van Maldergem syndrome 1Open Targets
0.74Strong
mitral valve prolapseOpen Targets
0.67Moderate
Cerebro-facio-articular syndromeOpen Targets
0.63Moderate
mitral valve prolapse, myxomatous 2Open Targets
0.58Moderate
Periventricular heterotopiaOpen Targets
0.55Moderate
familial mitral valve prolapseOpen Targets
0.37Weak
periventricular nodular heterotopiaOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.36Weak
Abnormality of the skeletal systemOpen Targets
0.26Weak
alcohol drinkingOpen Targets
0.22Weak
genetic disorderOpen Targets
0.19Weak
van Maldergem syndromeOpen Targets
0.19Weak
congenital heart diseaseOpen Targets
0.18Weak
lymphedemaOpen Targets
0.17Weak
cardiomyopathyOpen Targets
0.12Weak
myoepithelial tumorOpen Targets
0.11Weak
cancerOpen Targets
0.08Suggestive
inherited hemoglobinopathyOpen Targets
0.07Suggestive
infectionOpen Targets
0.07Suggestive
congenital left-sided heart lesionsOpen Targets
0.06Suggestive
Mitral valve prolapse 2UniProt
Van Maldergem syndrome 1UniProt
Pathogenic Variants40
NM_003737.4(DCHS1):c.6988C>T (p.Arg2330Cys)Pathogenic
Mitral valve prolapse, myxomatous 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 2330
NM_003737.4(DCHS1):c.6421C>T (p.Arg2141Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 2141
NM_003737.4(DCHS1):c.3782_3825del (p.Ser1261fs)Pathogenic
DCHS1-Related Disorders
β˜…β˜†β˜†β˜†2025β†’ Residue 1261
NM_003737.4(DCHS1):c.6403G>T (p.Glu2135Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 2135
NM_003737.4(DCHS1):c.3901C>T (p.Arg1301Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1301
NM_003737.4(DCHS1):c.5580C>A (p.Tyr1860Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1860
NM_003737.4(DCHS1):c.5212C>T (p.Arg1738Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 1738
NM_003737.4(DCHS1):c.2995C>T (p.Arg999Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 999
NM_003737.4(DCHS1):c.61del (p.Leu21fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 21
NM_003737.4(DCHS1):c.6576+1G>TLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_003737.4(DCHS1):c.6094C>T (p.Arg2032Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 2032
NM_003737.4(DCHS1):c.6759_6772del (p.Ser2254fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 2254
NM_003737.4(DCHS1):c.286G>T (p.Glu96Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 96
NM_003737.4(DCHS1):c.3436C>T (p.Gln1146Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 1146
NM_003737.4(DCHS1):c.3916C>T (p.Gln1306Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 1306
NM_003737.4(DCHS1):c.5624_5627dup (p.Gln1876fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 1876
NM_003737.4(DCHS1):c.781dup (p.His261fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 261
NM_003737.4(DCHS1):c.3839del (p.Ile1280fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 1280
NM_003737.4(DCHS1):c.5035+2T>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2024
NM_003737.4(DCHS1):c.2258del (p.Asn753fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 753
View on ClinVar β†—
Related Genes
CTNND1Protein interaction100%CTNNB1Protein interaction100%DCHS2Protein interaction91%CDH17Protein interaction80%CTNNA1Protein interaction80%CTNNA2Protein interaction80%
Tissue Expression6 tissues
Ovary
100%
Heart
90%
Lung
56%
Brain
51%
Bone Marrow
16%
Liver
13%
Gene Interaction Network
Click a node to explore
DCHS1CTNND1CTNNB1DCHS2CDH17CTNNA1CTNNA2
PROTEIN STRUCTURE
Preparing viewer…
PDB8EGW Β· 2.30 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.49Moderately Constrained
pLIβ“˜
0.33Tolerant
Observed/Expected LoF0.41 [0.34–0.49]
RankingsWhere DCHS1 stands among ~20K protein-coding genes
  • #12,771of 20,598
    Most Researched26
  • #1,553of 5,498
    Most Pathogenic Variants40
  • #2,901of 17,882
    Most Constrained (LOEUF)0.49 Β· top quartile
Genes detectedDCHS1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Neuronal hyperactivity in neurons derived from individuals with gray matter heterotopia.
PMID: 39966398
Nat Commun Β· 2025
1.00
2
DCHS1, Lix1L, and the Septin Cytoskeleton: Molecular and Developmental Etiology of Mitral Valve Prolapse.
PMID: 35200715
J Cardiovasc Dev Dis Β· 2022
0.90
3
DCHS1 Modulates Forebrain Proportions in Modern Humans via a Glycosylation Change.
PMID: 40463223
bioRxiv Β· 2025
0.80
4
Genetic background of mitral valve prolapse.
PMID: 35345263
Rev Cardiovasc Med Β· 2022
0.70
5
Genetic heterogeneity in familial forms of genetic generalized epilepsy: from mono- to oligogenism.
PMID: 39574152
Hum Genomics Β· 2024
0.60