Hereditary neuropathy or pain disorder

Gene: XPNPEP3

I don't know

Comment on list classification: 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).

In the literature, there are 2 cases with peripheral neuropathy and biallelic variants in this gene (PMID: 38035175; 40953058), however, this is not a common manifestation for this gene. One case did not have any typical renal features and therefore it's worth monitoring for similar reports. In the meantime rating as Amber awaiting further corroborating cases.

Created: 13 Oct 2025, 10:26 a.m. | Last Modified: 13 Oct 2025, 10:26 a.m.

Panel Version: 7.14

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephronophthisis-like nephropathy 1, OMIM:613159; Peripheral neuropathy, MONDO:0005244; myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis, MONDO:0859322

Publications

• 38035175
• 40953058

I don't know

Currently sensory axonal neuropathy only reported in a single case.
Sources: Other

Created: 21 Sep 2025, 10 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephronopthisis; brain white matter lesions; sensory axonal neuropathy; recurrent rhabdomyolysis; cardiomyopathy; ataxia; hearing loss

Publications

• 40953058