DCHS1

dachsous cadherin-related 1, the group of Cadherin related

Basic information

Region (hg38): 11:6621330-6655809

Previous symbols: [ "CDH25", "PCDH16" ]

Links

ENSG00000166341 ∙ NCBI:8642 ∙ OMIM:603057 ∙ HGNC:13681 ∙ Uniprot:Q96JQ0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• van Maldergem syndrome 1 (Strong), mode of inheritance: AR
• familial mitral valve prolapse (Supportive), mode of inheritance: AD
• van Maldergem syndrome (Supportive), mode of inheritance: AR
• mitral valve prolapse, myxomatous 2 (Strong), mode of inheritance: AD
• van Maldergem syndrome 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitral valve prolapse 2; Van Maldegrem syndrome 1	AD/AR	Audiologic/Otolaryngologic; Cardiovascular	For Mitral valve prolapse, individuals may manifest with severe mitral valve prolapse leading to heart failure and requiring surgery, and awareness may allow prompt diagnosis and management; For Van Maldegrem syndrome, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Renal	12707861; 24056717; 26258302

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DCHS1 gene.

• not_provided (1997 variants)
• Inborn_genetic_diseases (495 variants)
• DCHS1-related_disorder (106 variants)
• Van_Maldergem_syndrome_1 (63 variants)
• not_specified (44 variants)
• Mitral_valve_prolapse,_myxomatous_2 (30 variants)
• Congenital_heart_disease (7 variants)
• Lymphedema (4 variants)
• DCHS1-related_congenital_anomalies_of_the_kidney_and_urinary_tract (2 variants)
• Cardiomyopathy (1 variants)
• Myoepithelial_tumor (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DCHS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003737.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	563	23	592
missense	1	2	1296	118	15	1432
nonsense	13	3	7			23
start loss			1			1
frameshift	9	1	9			19
splice donor/acceptor (+/-2bp)		3				3
Total	23	9	1319	681	38

Highest pathogenic variant AF is 0.0000334659

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DCHS1	protein_coding	protein_coding	ENST00000299441	20	34530

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000290	125563	0	30	125593	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.40	1630	1.93e+3	0.846	0.000125	20449
Missense in Polyphen		571	776.79	0.73507		8914
Synonymous	1.50	756	810	0.933	0.0000505	7695
Loss of Function	7.64	15	95.6	0.157	0.00000637	978

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000210	0.000210
Ashkenazi Jewish	0.000299	0.000298
East Asian	0.0000648	0.0000544
Finnish	0.000239	0.000231
European (Non-Finnish)	0.000111	0.000106
Middle Eastern	0.0000648	0.0000544
South Asian	0.000152	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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). {ECO:0000269|PubMed:26258302}.
• Disease: DISEASE: Mitral valve prolapse 2 (MVP2) [MIM:607829]: A form of mitral valve prolapse, a valvular hearth disease characterized by abnormally elongated and thickened mitral valve leaflets, that typically show myxomatous degeneration with increased leaflet compliance. It is associated with mitral regurgitation. Myxomatous mitral valves have an abnormal layered architecture characterized by loose collagen in fibrosa, expanded spongiosa strongly positive for proteoglycans, and disrupted elastin in atrialis. In classic mitral valve prolapse, leaflets are at least 5 mm thick, whereas in the non-classic form, they are less than 5 mm thick. Severe classic mitral valve prolapse is strongly associated with arrhythmias, endocarditis, heart failure, and need for valve surgery. {ECO:0000269|PubMed:26258302}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Hippo signaling pathway - multiple species - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.131

Intolerance Scores

• loftool: 0.261
• rvis_EVS: -1.38
• rvis_percentile_EVS: 4.4

Haploinsufficiency Scores

• pHI: 0.330
• hipred: Y
• hipred_score: 0.623
• ghis: 0.529

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.580

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dchs1
• Phenotype: growth/size/body region phenotype; respiratory system phenotype; embryo phenotype; renal/urinary system phenotype; skeleton phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: dchs1b
• Affected structure: fertilized egg
• Phenotype tag: abnormal
• Phenotype quality: disoriented

Gene ontology

• Biological process: branching involved in ureteric bud morphogenesis;mitral valve formation;cell migration involved in endocardial cushion formation;homophilic cell adhesion via plasma membrane adhesion molecules;heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules;pattern specification process;calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules;neural tube development;neurogenesis;hippo signaling;post-anal tail morphogenesis;ossification involved in bone maturation;digestive tract development;condensed mesenchymal cell proliferation;protein localization to plasma membrane;cochlea development
• Cellular component: plasma membrane;membrane;integral component of membrane;apical part of cell
• Molecular function: calcium ion binding