Rhabdomyolysis and metabolic muscle disorders

Gene: XPNPEP3

Red List (low evidence)

Biallelic variants in this gene are associated with nephronophthisis, a progressive cystic kidney disorder that leads to end-stage renal disease (OMIM:613159). Extra-renal manifestations have only been reported in a subset of cases - neurological features have been reported in at least 4 unrelated families including tremor, dystonia, rhabdomyolysis, peripheral neuropathy, sensorineural hearing loss, epilepsy and cardiomyopathy. Kidney disease was present in all (PMID: 20179356; 38035175), except one case (PMID: 40953058).

A recent report (PMID: 40953058) included the first case of mitochondrial myopathy presenting with a purely metabolic phenotype, manifesting as exertional symptoms and rhabdomyolysis associated with a homozygous XPNPEP3 variant (c.1153dup, p.(Tyr385LeufsTer13)) - however, this individual did not have any typical renal features and therefore it's worth monitoring for similar reports. In the meantime rating as Red awaiting further corroborating cases.
Sources: Literature

Created: 13 Oct 2025, 11:06 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MONDO:0859322

Publications

• 40953058