Cardiac valvular dysplasia 2

Summary

Cardiac valvular dysplasia 2 (MONDO:0859572) is a disease caused by ADAMTS19 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: ADAMTS19 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cardiac valvular dysplasia 2
Mondo ID	MONDO:0859572
OMIM	620067
UMLS	C5774226
MedGen	1823999
Is cancer (heuristic)	no

Data availability: 10 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › cardiac valvular defect › cardiac valvular dysplasia 2

Related subtypes (1): cardiac valvular defect, developmental

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

10 retrieved; paginated sample, class counts are floors:

4 pathogenic, 4 uncertain significance, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1707568	NM_133638.6(ADAMTS19):c.1984C>T (p.Arg662Ter)	ADAMTS19	Pathogenic	no assertion criteria provided
1707569	NM_133638.6(ADAMTS19):c.2003+1G>T	ADAMTS19	Pathogenic	no assertion criteria provided
1707571	NM_133638.6(ADAMTS19):c.1957C>T (p.Arg653Ter)	ADAMTS19	Pathogenic	no assertion criteria provided
4845660	NM_133638.6(ADAMTS19):c.2425+1G>A	ADAMTS19	Pathogenic	criteria provided, single submitter
3897987	NM_133638.6(ADAMTS19):c.1478+1G>A	ADAMTS19	Likely pathogenic	criteria provided, single submitter
4849330	NM_133638.6(ADAMTS19):c.2922dup (p.Arg975fs)	ADAMTS19	Likely pathogenic	criteria provided, single submitter
1707570	NM_133638.6(ADAMTS19):c.3538C>T (p.Arg1180Ter)	ADAMTS19	Uncertain significance	criteria provided, single submitter
3236630	NM_133638.6(ADAMTS19):c.1596G>C (p.Lys532Asn)	ADAMTS19	Uncertain significance	criteria provided, single submitter
3238751	NM_133638.6(ADAMTS19):c.2423C>T (p.Ala808Val)	ADAMTS19	Uncertain significance	criteria provided, single submitter
3238775	NM_133638.6(ADAMTS19):c.3107G>A (p.Arg1036His)	ADAMTS19	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
ADAMTS19	Strong	Autosomal recessive	cardiac valvular dysplasia 2	4

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
ADAMTS19	HGNC:17111	ENSG00000145808	Q8TE59	A disintegrin and metalloproteinase with thrombospondin motifs 19	gencc,clinvar

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Protease	1	36.6×	0.027

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ADAMTS19	Protease	yes		TSP1_rpt, Peptidase_M12B, ADAM_Cys-rich

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
adrenal tissue	1
body of uterus	1
buccal mucosa cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ADAMTS19	137	broad	marker	adrenal tissue, buccal mucosa cell, body of uterus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ADAMTS19	680

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ADAMTS19	Q8TE59	68.76

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective B3GALTL causes PpS	1	308.6×	0.003	ADAMTS19
O-glycosylation of TSR domain-containing proteins	1	300.5×	0.003	ADAMTS19

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
tricuspid valve morphogenesis	1	3370.4×	0.002	ADAMTS19
mitral valve morphogenesis	1	1685.2×	0.002	ADAMTS19
pulmonary valve morphogenesis	1	936.2×	0.003	ADAMTS19
aortic valve morphogenesis	1	432.1×	0.004	ADAMTS19
ventricular septum morphogenesis	1	432.1×	0.004	ADAMTS19
collagen fibril organization	1	224.7×	0.006	ADAMTS19
extracellular matrix organization	1	122.1×	0.009	ADAMTS19
proteolysis	1	34.2×	0.029	ADAMTS19

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
ADAMTS19	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	1	ADAMTS19
E	Difficult family or no structure, no drug	0

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)
ADAMTS19	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.