long QT syndrome 9

Summary

long QT syndrome 9 (MONDO:0012736) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 35

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	long QT syndrome 9
Mondo ID	MONDO:0012736
MeSH	C567515
OMIM	611818
DOID	DOID:0110650
UMLS	C2678485
MedGen	395635
GARD	0010435
Is cancer (heuristic)	no

Also known as: CAV3 long QT syndrome · long QT syndrome 9 · long QT syndrome caused by mutation in CAV3 · long QT syndrome type 9 · LQT9

Data availability: 35 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › long QT syndrome › familial long QT syndrome › long QT syndrome 9

Related subtypes (18): Jervell and Lange-Nielsen syndrome, Andersen-Tawil syndrome, cardiac arrhythmia, ankyrin-B-related, Timothy syndrome, long QT syndrome 3, long QT syndrome 10, long QT syndrome 11, long QT syndrome 12, long QT syndrome 13, long QT syndrome 2, long QT syndrome 6, long QT syndrome 5, long QT syndrome 14, long QT syndrome 15, long QT syndrome 8, long QT syndrome 16, long QT syndrome 1, long QT syndrome 4

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

35 retrieved; paginated sample, class counts are floors:

23 uncertain significance, 5 pathogenic, 3 conflicting classifications of pathogenicity, 2 benign/likely benign, 1 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
31740	NM_033337.3(CAV3):c.114+2T>C	CAV3	Pathogenic	criteria provided, multiple submitters, no conflicts
8283	NM_033337.3(CAV3):c.80G>A (p.Arg27Gln)	CAV3	Pathogenic	criteria provided, multiple submitters, no conflicts
8291	NM_033337.3(CAV3):c.423C>G (p.Ser141Arg)	CAV3	Pathogenic	no assertion criteria provided
8295	NM_033337.3(CAV3):c.40G>C (p.Val14Leu)	CAV3	Pathogenic	no assertion criteria provided
8294	NM_033337.3(CAV3):c.253G>A (p.Ala85Thr)	OXTR	Pathogenic	no assertion criteria provided
973213	NM_033337.3(CAV3):c.299T>A (p.Ile100Asn)	CAV3	Likely pathogenic	criteria provided, single submitter
8279	NM_033337.2(CAV3):c.216C>G (p.Cys72Trp)	CAV3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
8285	NM_033337.3(CAV3):c.277G>A (p.Ala93Thr)	CAV3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
8293	NM_033337.3(CAV3):c.233C>T (p.Thr78Met)	CAV3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1025525	NM_033337.3(CAV3):c.247C>T (p.Pro83Ser)	CAV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1025712	NM_033337.3(CAV3):c.35A>G (p.Gln12Arg)	CAV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1299390	NM_033337.3(CAV3):c.22G>A (p.Asp8Asn)	CAV3	Uncertain significance	criteria provided, single submitter
180800	NM_033337.3(CAV3):c.433G>A (p.Val145Met)	CAV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
346863	NM_033337.3(CAV3):c.*852G>A	CAV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
409256	NM_033337.3(CAV3):c.221G>A (p.Arg74His)	CAV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
409259	NM_033337.3(CAV3):c.143C>G (p.Pro48Arg)	CAV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
457130	NM_033337.3(CAV3):c.254C>T (p.Ala85Val)	CAV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
637987	NM_033337.3(CAV3):c.89A>G (p.Lys30Arg)	CAV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
8296	NM_033337.3(CAV3):c.236T>G (p.Leu79Arg)	CAV3	Uncertain significance	criteria provided, single submitter
900587	NM_033337.3(CAV3):c.*134G>A	CAV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
903140	NM_033337.3(CAV3):c.*658T>A	CAV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
1349629	NM_033337.3(CAV3):c.310G>C (p.Val104Leu)	OXTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
279736	NM_033337.3(CAV3):c.401C>T (p.Ala134Val)	OXTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
288112	NM_033337.3(CAV3):c.400G>A (p.Ala134Thr)	OXTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
346854	NM_033337.3(CAV3):c.*592G>A	OXTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
346857	NM_033337.3(CAV3):c.*741G>A	OXTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
346862	NM_033337.3(CAV3):c.*834A>T	OXTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
409254	NM_033337.3(CAV3):c.182G>A (p.Ser61Asn)	OXTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
409255	NM_033337.3(CAV3):c.125A>C (p.Glu42Ala)	OXTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
840845	NM_033337.3(CAV3):c.310G>A (p.Val104Met)	OXTR	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 4 · 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
CAV3	Moderate	Autosomal dominant	long QT syndrome 9	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CAV3	Orphanet:101016	Romano-Ward syndrome
CAV3	Orphanet:206599	Isolated asymptomatic elevation of creatine phosphokinase
CAV3	Orphanet:488650	Distal myopathy, Tateyama type
CAV3	Orphanet:97238	Rippling muscle disease

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CAV3	HGNC:1529	ENSG00000182533	P56539	Caveolin-3	gencc,clinvar
OXTR	HGNC:8529	ENSG00000180914	P30559	Oxytocin receptor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CAV3	Caveolin-3	May act as a scaffolding protein within caveolar membranes.
OXTR	Oxytocin receptor	Receptor for oxytocin.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
GPCR	1	12.0×	0.164
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CAV3	Other/Unknown	no		Caveolin, Caveolin_CS
OXTR	GPCR	yes		GPCR_Rhodpsn, Vasoprsn_rcpt, Oxytocn_rcpt

Expression context

Cohort genes with no expression data: 0.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	1
triceps brachii	1
vastus lateralis	1
bronchial epithelial cell	1
decidua	1
epithelium of mammary gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CAV3	157	tissue_specific	yes	hindlimb stylopod muscle, vastus lateralis, triceps brachii
OXTR	204	broad	yes	decidua, bronchial epithelial cell, epithelium of mammary gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CAV3	2,369
OXTR	1,420

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
OXTR	P30559	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CAV3	P56539	88.54

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Vasopressin-like receptors	1	951.7×	0.004	OXTR
Smooth Muscle Contraction	1	132.8×	0.015	CAV3
Muscle contraction	1	38.6×	0.034	CAV3
G alpha (q) signalling events	1	28.7×	0.035	OXTR

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of signal transduction by receptor internalization	1	8426.0×	0.002	CAV3
regulation of nerve growth factor receptor activity	1	8426.0×	0.002	CAV3
negative regulation of sarcomere organization	1	8426.0×	0.002	CAV3
negative regulation of membrane depolarization during cardiac muscle cell action potential	1	8426.0×	0.002	CAV3
nucleus localization	1	2106.5×	0.003	CAV3
regulation of membrane depolarization during cardiac muscle cell action potential	1	2106.5×	0.003	CAV3
positive regulation of caveolin-mediated endocytosis	1	2106.5×	0.003	CAV3
regulation of systemic arterial blood pressure by vasopressin	1	1685.2×	0.003	OXTR
membrane raft organization	1	1685.2×	0.003	CAV3
maternal process involved in parturition	1	1685.2×	0.003	OXTR
regulation of branching involved in mammary gland duct morphogenesis	1	1685.2×	0.003	CAV3
regulation of skeletal muscle contraction	1	1404.3×	0.003	CAV3
T-tubule organization	1	1404.3×	0.003	CAV3
regulation of ventricular cardiac muscle cell membrane depolarization	1	1404.3×	0.003	CAV3
cellular response to ionomycin	1	1404.3×	0.003	CAV3
detection of muscle stretch	1	1203.7×	0.004	CAV3
regulation of p38MAPK cascade	1	1203.7×	0.004	CAV3
caveola assembly	1	1053.2×	0.004	CAV3
regulation of calcium ion import	1	1053.2×	0.004	CAV3
regulation of cardiac muscle cell action potential involved in regulation of contraction	1	936.2×	0.004	CAV3
cardiac muscle hypertrophy	1	842.6×	0.004	CAV3
negative regulation of cell size	1	842.6×	0.004	CAV3
negative regulation of calcium ion transport	1	842.6×	0.004	CAV3
positive regulation of myotube differentiation	1	766.0×	0.004	CAV3
negative regulation of cell growth involved in cardiac muscle cell development	1	702.2×	0.004	CAV3
negative regulation of potassium ion transmembrane transport	1	702.2×	0.004	CAV3
negative regulation of protein localization to cell surface	1	648.1×	0.004	CAV3
negative regulation of cardiac muscle hypertrophy	1	561.7×	0.004	CAV3
heart trabecula formation	1	561.7×	0.004	CAV3
positive regulation of blood pressure	1	526.6×	0.004	OXTR

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
OXTR	DESMOPRESSIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
OXTR	15	4
CAV3	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
DESMOPRESSIN	4	OXTR
CARBETOCIN	4	OXTR
VASOPRESSIN	4	OXTR
ATOSIBAN	4	OXTR
OXYTOCIN	4	OXTR
MOZAVAPTAN	4	OXTR
NOLASIBAN	3	OXTR
SEMAXANIB	3	OXTR
RETOSIBAN	3	OXTR
LIXIVAPTAN	3	OXTR
SELEPRESSIN	2	OXTR
ORNIPRESSIN	2	OXTR
EPELSIBAN	2	OXTR
PECAVAPTAN	2	OXTR
NELIVAPTAN	2	OXTR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
OXTR	249	Binding:149, Functional:99, Unclassified:1

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
OXTR	249

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

15 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.

Compound	Max phase	Cohort target (bioactivity)
DESMOPRESSIN	4	OXTR
CARBETOCIN	4	OXTR
VASOPRESSIN	4	OXTR
ATOSIBAN	4	OXTR
OXYTOCIN	4	OXTR
MOZAVAPTAN	4	OXTR
NOLASIBAN	3	OXTR
SEMAXANIB	3	OXTR
RETOSIBAN	3	OXTR
LIXIVAPTAN	3	OXTR
SELEPRESSIN	2	OXTR
ORNIPRESSIN	2	OXTR
EPELSIBAN	2	OXTR
PECAVAPTAN	2	OXTR
NELIVAPTAN	2	OXTR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	OXTR
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	CAV3

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)
CAV3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.