Inherited rippling muscle disease

Summary

Inherited rippling muscle disease (MONDO:0020704) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	inherited rippling muscle disease
Mondo ID	MONDO:0020704
GARD	0025217
MedDRA	10069417
Is cancer (heuristic)	no

Also known as: rippling muscle disease · RMD

Data availability: 1 GenCC gene-disease record · 3 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › rippling muscle disease › inherited rippling muscle disease

Related subtypes (1): acquired rippling muscle disease

Subtypes (2): rippling muscle disease 1, rippling muscle disease 2

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

No tiered GWAS variants or ClinVar records for this disease.

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	rippling muscle disease 2	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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CAV3	HGNC:1529	ENSG00000182533	P56539	Caveolin-3	gencc

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.

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)
CAV3	Other/Unknown	no		Caveolin, Caveolin_CS

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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
hindlimb stylopod muscle	1
triceps brachii	1
vastus lateralis	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CAV3	2,369

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
CAV3	P56539	88.54

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
Smooth Muscle Contraction	1	265.6×	0.008	CAV3
Muscle contraction	1	77.2×	0.013	CAV3

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
regulation of signal transduction by receptor internalization	1	16852.0×	9e-04	CAV3
regulation of nerve growth factor receptor activity	1	16852.0×	9e-04	CAV3
negative regulation of sarcomere organization	1	16852.0×	9e-04	CAV3
negative regulation of membrane depolarization during cardiac muscle cell action potential	1	16852.0×	9e-04	CAV3
nucleus localization	1	4213.0×	0.002	CAV3
regulation of membrane depolarization during cardiac muscle cell action potential	1	4213.0×	0.002	CAV3
positive regulation of caveolin-mediated endocytosis	1	4213.0×	0.002	CAV3
membrane raft organization	1	3370.4×	0.002	CAV3
regulation of branching involved in mammary gland duct morphogenesis	1	3370.4×	0.002	CAV3
regulation of skeletal muscle contraction	1	2808.7×	0.002	CAV3
T-tubule organization	1	2808.7×	0.002	CAV3
regulation of ventricular cardiac muscle cell membrane depolarization	1	2808.7×	0.002	CAV3
cellular response to ionomycin	1	2808.7×	0.002	CAV3
detection of muscle stretch	1	2407.4×	0.002	CAV3
regulation of p38MAPK cascade	1	2407.4×	0.002	CAV3
caveola assembly	1	2106.5×	0.002	CAV3
regulation of calcium ion import	1	2106.5×	0.002	CAV3
regulation of cardiac muscle cell action potential involved in regulation of contraction	1	1872.4×	0.002	CAV3
cardiac muscle hypertrophy	1	1685.2×	0.002	CAV3
negative regulation of cell size	1	1685.2×	0.002	CAV3
negative regulation of calcium ion transport	1	1685.2×	0.002	CAV3
positive regulation of myotube differentiation	1	1532.0×	0.002	CAV3
negative regulation of cell growth involved in cardiac muscle cell development	1	1404.3×	0.002	CAV3
negative regulation of potassium ion transmembrane transport	1	1404.3×	0.002	CAV3
negative regulation of protein localization to cell surface	1	1296.3×	0.002	CAV3
negative regulation of cardiac muscle hypertrophy	1	1123.5×	0.002	CAV3
heart trabecula formation	1	1123.5×	0.002	CAV3
regulation of sodium ion transmembrane transport	1	1053.2×	0.002	CAV3
ventricular cardiac muscle cell action potential	1	991.3×	0.002	CAV3
plasma membrane organization	1	887.0×	0.002	CAV3

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
CAV3	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	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.