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An autosomal dominant condition caused by mutation(s) in the CAV3 gene, encoding caveolin-3. It is characterized by mechanically triggered contractions of skeletal muscles. Limb-girdle muscular dystrophy type 1C is an allelic disorder with an overlapping phenotype.
Features include always present findings: Elevated creatine kinase (muscle enzyme) (elevated circulating creatine kinase concentration), Gowers sign, Enlarged calf muscles (calf muscle hypertrophy), and Proximal muscle weakness; and sometimes findings: Exercise-induced muscle cramps. 12 total HPO annotations.
Organ System | Phenotype Count | Example Features |
|---|---|---|
Muscles | 10 | Percussion-induced rapid rolling muscle contractions, Gowers sign, Enlarged calf muscles (calf muscle hypertrophy) |
Lab test results | 2 | Elevated creatine kinase (muscle enzyme) (elevated circulating creatine kinase concentration), Abnormal electrical muscle activity (EMG) (emg abnormality) |
Bones and joints | 1 | Skeletal muscle hypertrophy |
Age of onset: adulthood.
CAV3 encodes caveolin 3 (151 aa). May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. Highest expression in Muscle Skeletal (46.5 TPM) and Heart Left Ventricle (13.0 TPM).
Rippling muscle disease 2 is associated with mutations in the CAV3 gene on chromosome 3.
The CAV3 protein participates in DYSF, CAV3 and TRIM72 bind, CaV3.2 (CACNA1H:CACNA2D1:CACNB1,2,3:CACNG7) transports calcium from the extracellular region to the cytosol, and CaV3.2:heparan sulfate-HSPG2 pathways.
CAV3 is classified as a druggable target (Cell Surface and Transporter categories) with score 0.0.
Genetic testing for CAV3 is available. Testing is considered confirmatory for diagnosis.
Phenotype severity distribution: 4 always present features.
Estimated prevalence: <1 in 1,000,000 (VERY_RARE).
No clinical trials have been registered for rippling muscle disease 2.
3 publications have been identified in PubMed for rippling muscle disease 2. Research spans Review / Meta-Analysis (33%), Case Report / Case Series (33%), and Basic Science / Preclinical (33%).
Shen Y (2025). [PMID: 40695747](https://pubmed.ncbi.nlm.nih.gov/40695747/). *Neuropathology*. [Case Report / Case Series]
Nath SR (2025). [PMID: 39819455](https://pubmed.ncbi.nlm.nih.gov/39819455/). *Acta Neuropathol Commun*. [Basic Science / Preclinical]
Rashed HR (2025). [PMID: 39370631](https://pubmed.ncbi.nlm.nih.gov/39370631/). *Muscle Nerve*. [Review / Meta-Analysis]
Data assembled from 6 of 12 sources · Last updated Sep 19, 2026, 3:32 AM UTC
Online Mendelian Inheritance in Man
European rare disease database
Genetic and Rare Diseases Info Center
AI-curated news mentioning rippling muscle disease 2
Updated Feb 13, 2026
A recent publication discusses clinical support and education initiatives for muscle diseases in Japan and other Asian regions. The findings highlight the importance of tailored educational programs to improve patient care and outcomes.