Mitral valve prolapse, myxomatous 2

Summary

Mitral valve prolapse, myxomatous 2 (MONDO:0011915) is a disease caused by DCHS1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: DCHS1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 30

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	mitral valve prolapse, myxomatous 2
Mondo ID	MONDO:0011915
MeSH	C564326
OMIM	607829
UMLS	C1843003
MedGen	335856
GARD	0015421
Is cancer (heuristic)	no

Also known as: mitral valve prolapse, myxomatous 2 · MMVP2 · MVP2

Data availability: 30 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart valve disorder › mitral valve disorder › mitral valve prolapse › familial mitral valve prolapse › mitral valve prolapse, myxomatous 2

Related subtypes (2): mitral valve prolapse, myxomatous 3, MVP1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

30 retrieved; paginated sample, class counts are floors:

24 uncertain significance, 2 conflicting classifications of pathogenicity, 1 pathogenic, 1 likely benign, 1 pathogenic/likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1028154	NM_003737.4(DCHS1):c.5679C>A (p.Tyr1893Ter)	DCHS1	Pathogenic	criteria provided, single submitter
217871	NM_003737.4(DCHS1):c.6988C>T (p.Arg2330Cys)	DCHS1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1107906	NM_003737.4(DCHS1):c.8302C>T (p.Arg2768Cys)	DCHS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1297585	NM_003737.4(DCHS1):c.8186A>T (p.His2729Leu)	DCHS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1028152	NM_003737.4(DCHS1):c.1442C>A (p.Pro481His)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1028153	NM_003737.4(DCHS1):c.4798G>T (p.Ala1600Ser)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1028650	NM_003737.4(DCHS1):c.3785A>T (p.Glu1262Val)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033606	NM_003737.4(DCHS1):c.3416G>C (p.Arg1139Pro)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033607	NM_003737.4(DCHS1):c.5809G>T (p.Ala1937Ser)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033608	NM_003737.4(DCHS1):c.6209G>T (p.Arg2070Leu)	DCHS1	Uncertain significance	criteria provided, single submitter
1033609	NM_003737.4(DCHS1):c.6415C>T (p.Arg2139Trp)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1033610	NM_003737.4(DCHS1):c.994G>A (p.Val332Met)	DCHS1	Uncertain significance	criteria provided, single submitter
1363973	NM_003737.4(DCHS1):c.2932C>T (p.Arg978Cys)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1391575	NM_003737.4(DCHS1):c.8449G>C (p.Ala2817Pro)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1391576	NM_003737.4(DCHS1):c.6599A>C (p.Gln2200Pro)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1424196	NM_003737.4(DCHS1):c.1457C>T (p.Ala486Val)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1429580	NM_003737.4(DCHS1):c.7537C>T (p.Arg2513Cys)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1493677	NM_003737.4(DCHS1):c.3898C>T (p.Pro1300Ser)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2441984	NM_003737.4(DCHS1):c.1330G>T (p.Ala444Ser)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2505282	NM_003737.4(DCHS1):c.5851C>A (p.Arg1951Ser)	DCHS1	Uncertain significance	criteria provided, single submitter
3065328	NM_003737.4(DCHS1):c.6380G>C (p.Arg2127Pro)	DCHS1	Uncertain significance	criteria provided, single submitter
3065424	NM_003737.4(DCHS1):c.9145G>C (p.Glu3049Gln)	DCHS1	Uncertain significance	criteria provided, single submitter
3080456	NM_003737.4(DCHS1):c.7649C>A (p.Ala2550Glu)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3252754	NM_003737.4(DCHS1):c.9424T>C (p.Cys3142Arg)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3391120	NM_003737.4(DCHS1):c.9649C>T (p.Pro3217Ser)	DCHS1	Uncertain significance	criteria provided, single submitter
3600143	NM_003737.4(DCHS1):c.2458C>T (p.Arg820Cys)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3600519	NM_003737.4(DCHS1):c.8521G>T (p.Asp2841Tyr)	DCHS1	Uncertain significance	criteria provided, single submitter
983077	NM_003737.4(DCHS1):c.4552C>T (p.Arg1518Trp)	DCHS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
217870	NM_003737.4(DCHS1):c.7538G>A (p.Arg2513His)	DCHS1	Likely benign	criteria provided, single submitter
723316	NM_003737.4(DCHS1):c.3481+9A>T	DCHS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DCHS1	Strong	Autosomal dominant	mitral valve prolapse, myxomatous 2	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DCHS1	Orphanet:314679	Cerebrofacioarticular syndrome
DCHS1	Orphanet:741	Familial mitral valve prolapse

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DCHS1	HGNC:13681	ENSG00000166341	Q96JQ0	Protocadherin-16	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DCHS1	Protocadherin-16	Calcium-dependent cell-adhesion protein.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DCHS1	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	1
ganglionic eminence	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DCHS1	259	broad	marker	tendon of biceps brachii, ganglionic eminence, cortical plate

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DCHS1	1,356

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DCHS1	Q96JQ0	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
mitral valve formation	1	5617.3×	0.001	DCHS1
condensed mesenchymal cell proliferation	1	5617.3×	0.001	DCHS1
cell migration involved in endocardial cushion formation	1	4213.0×	0.001	DCHS1
septin cytoskeleton organization	1	4213.0×	0.001	DCHS1
ossification involved in bone maturation	1	1404.3×	0.003	DCHS1
obsolete cell-cell adhesion via plasma-membrane adhesion molecules	1	1123.5×	0.003	DCHS1
hippo signaling	1	732.7×	0.003	DCHS1
post-anal tail morphogenesis	1	732.7×	0.003	DCHS1
neural tube development	1	526.6×	0.003	DCHS1
digestive tract development	1	526.6×	0.003	DCHS1
calcium-dependent cell-cell adhesion	1	481.5×	0.003	DCHS1
pattern specification process	1	468.1×	0.003	DCHS1
cochlea development	1	468.1×	0.003	DCHS1
branching involved in ureteric bud morphogenesis	1	366.4×	0.004	DCHS1
heterophilic cell-cell adhesion	1	337.0×	0.004	DCHS1
neurogenesis	1	208.1×	0.006	DCHS1
homophilic cell-cell adhesion	1	140.4×	0.008	DCHS1
protein localization to plasma membrane	1	108.7×	0.010	DCHS1
gene expression	1	79.9×	0.013	DCHS1
cell migration	1	61.5×	0.016	DCHS1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DCHS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	DCHS1

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DCHS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.