Pulmonary valve stenosis

Summary

Pulmonary valve stenosis (MONDO:0006936) is a disease with 1 cohort gene and 9 clinical trials. Top therapeutic interventions include calcium gluconate and sodium citrate.

At a glance

• Cohort genes: 1
• ClinVar variants: 2
• Clinical trials: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pulmonary valve stenosis
Mondo ID	MONDO:0006936
EFO	EFO:1001138
MeSH	D011666
DOID	DOID:6420
ICD-11	611886666
UMLS	C0034089
MedGen	18768
MedDRA	10037450
Is cancer (heuristic)	no

Data availability: 2 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › cardiovascular disorder › heart disorder › heart valve disorder › pulmonary valve disorder › pulmonary valve stenosis

Related subtypes (2): pulmonary valve insufficiency, rheumatic pulmonary valve disease

Subtypes (2): pulmonary subvalvular stenosis, Hordnes Engebretsen Knudtson syndrome

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

2 retrieved; paginated sample, class counts are floors:

2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1120267	NM_018017.4(CCDC186):c.767C>G (p.Ser256Ter)	CCDC186	Pathogenic	criteria provided, single submitter
1684631	Single allele	LOC126862799	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
CCDC186	HGNC:24349	ENSG00000165813	Q7Z3E2	Coiled-coil domain-containing protein 186	clinvar

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)
CCDC186	Other/Unknown	no		CCDC186

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
calcaneal tendon	1
jejunal mucosa	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CCDC186	263	ubiquitous	marker	sperm, jejunal mucosa, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CCDC186	760

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CCDC186	Q7Z3E2	74.62

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
vesicle cytoskeletal trafficking	1	4213.0×	7e-04	CCDC186
insulin secretion involved in cellular response to glucose stimulus	1	1296.3×	0.001	CCDC186
response to bacterium	1	193.7×	0.005	CCDC186

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
CCDC186	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	CCDC186

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)
CCDC186	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 9.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	9

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03441971	Not specified	ACTIVE_NOT_RECRUITING	Evaluation of the GORE PV1 Device in Patients With Pulmonary Valve Dysfunction
NCT03983512	Not specified	ACTIVE_NOT_RECRUITING	PULSTA Transcatheter Pulmonary Valve Pre-Approval Study
NCT00004361	Not specified	COMPLETED	Study of the Relationship Between Calcium Levels and Intact Parathyroid Hormone (iPTH) in Adults With Repaired or Palliated Conotruncal Cardiac Defects
NCT00385112	Not specified	COMPLETED	Follow Up on Freestyle Valves in Children
NCT01092442	Not specified	COMPLETED	CryoValve SG Pulmonary Human Heart Valve Post Clearance Study
NCT02555319	Not specified	COMPLETED	A Feasibility Study to Evaluate the Safety and Short-term Effectiveness of Transcatheter Pulmonary Valve (TPV)
NCT02987387	Not specified	COMPLETED	COMPASSION XT PAS - Post-approval Study of the SAPIEN XT THV in Patients With Pulmonary Valve Dysfunction
NCT03110861	Not specified	COMPLETED	Pulsta® Transcatheter Pulmonary Valve Korean Multicenter Study
NCT05090228	Not specified	COMPLETED	Right Ventricle Remodeling After Pulmonary Valve Replacement and Percutaneous Pulmonary Valve Insertion

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CALCIUM GLUCONATE	4	1
SODIUM CITRATE	4	1