Caveolinopathy

Summary

Caveolinopathy (MONDO:0016146) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 53

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	caveolinopathy
Mondo ID	MONDO:0016146
Orphanet	207078
UMLS	C5679790
MedGen	1826055
GARD	0020394
Is cancer (heuristic)	no

Also known as: qualitative or quantitative defects of caveolin-3

Data availability: 53 ClinVar variants.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › caveolinopathy

Related subtypes (12): striated muscle rhabdoid tumor, septal myocardial infarction, tonsillar pillar cancer, atrophic muscular disease, cardiomyopathy, myalgic encephalomeyelitis/chronic fatigue syndrome, conduction system disorder, myostatin-related muscle hypertrophy, distal arthrogryposis, skeletal muscle disorder, myomatous neoplasm, Kocher-debre-Semelaigne syndrome

Subtypes (1): isolated asymptomatic elevation of creatine phosphokinase

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

53 retrieved; paginated sample, class counts are floors:

20 uncertain significance, 13 benign/likely benign, 10 conflicting classifications of pathogenicity, 10 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
136659	NM_033337.3(CAV3):c.201C>A (p.Val67=)	CAV3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
180801	NM_033337.3(CAV3):c.442C>T (p.Arg148Trp)	CAV3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
35804	NM_033337.3(CAV3):c.417C>T (p.Val139=)	CAV3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
377627	NM_033337.3(CAV3):c.*85C>A	CAV3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
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
900586	NM_033337.3(CAV3):c.*86G>A	CAV3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
46534	NM_033337.3(CAV3):c.276C>T (p.Phe92=)	OXTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
96240	NM_033337.3(CAV3):c.443G>A (p.Arg148Gln)	OXTR	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1037574	NM_033337.3(CAV3):c.165C>A (p.Asp55Glu)	CAV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
346849	NM_033337.3(CAV3):c.259C>T (p.Leu87Phe)	CAV3	Uncertain significance	criteria provided, single submitter
346852	NM_033337.3(CAV3):c.*433C>T	CAV3	Uncertain significance	criteria provided, single submitter
346853	NM_033337.3(CAV3):c.*467T>C	CAV3	Uncertain significance	criteria provided, single submitter
346855	NM_033337.3(CAV3):c.*722G>A	CAV3	Uncertain significance	criteria provided, single submitter
346863	NM_033337.3(CAV3):c.*852G>A	CAV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
8286	NM_033337.3(CAV3):c.290_292del (p.Phe97del)	CAV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
900583	NM_033337.3(CAV3):c.*13C>A	CAV3	Uncertain significance	criteria provided, single submitter
900587	NM_033337.3(CAV3):c.*134G>A	CAV3	Uncertain significance	criteria provided, multiple submitters, no conflicts
900588	NM_033337.3(CAV3):c.*193T>C	CAV3	Uncertain significance	criteria provided, single submitter
902269	NM_033337.3(CAV3):c.*312G>A	CAV3	Uncertain significance	criteria provided, single submitter
902271	NM_033337.3(CAV3):c.*435T>A	CAV3	Uncertain significance	criteria provided, single submitter
902272	NM_033337.3(CAV3):c.*440G>A	CAV3	Uncertain significance	criteria provided, single submitter
903140	NM_033337.3(CAV3):c.*658T>A	CAV3	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
346864	NM_033337.3(CAV3):c.*853T>C	OXTR	Uncertain significance	criteria provided, single submitter
8288	NM_033337.3(CAV3):c.191C>G (p.Thr64Ser)	OXTR	Uncertain significance	criteria provided, multiple submitters, no conflicts
902273	NM_033337.3(CAV3):c.*441T>C	OXTR	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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	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.