Mitochondrial disorders

Gene: XPNPEP3

I don't know

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains Amber.

Note from GMS reviewers: The phenotype arising from mutation of this gene is not that of mitochondrial disease. Not sure there is sufficient evidence that this can be classified as primary mitochondrial disease, but may be appropriate to include elsewhere in white matter disorders panel (C&S).

Created: 1 Feb 2023, 12:16 p.m. | Last Modified: 1 Feb 2023, 12:52 p.m.

Panel Version: 3.6

I don't know

Associated with relevant phenotype in OMIM and as limited Gen2Phen gene. At least three variants were reported in three unrelated cases (PMID: 32660933; 20179356). Two of the variants were terminating (RCV000000069, RCV001554332) and the third was a missense variant (RCV000000068), that seems to activate a cryptic splice site; RT-PCR of lymphoblastoid cells showed that this resulted in the inclusion of intronic bases and a frameshift. Cilia-related function was examined by the suppression of zebrafish xpnpep3, resulting in phenotypes reminiscent of ciliopathy morphants, this effect was rescued by human XPNPEP3 that was devoid of a mitochondrial localization signal (PMID: 20179356).

Created: 11 Jan 2022, 5:03 p.m. | Last Modified: 11 Jan 2022, 5:15 p.m.

Panel Version: 2.84

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review, however, Zornitza Stark (Australian Genomics) has commented that the phenotype is not strictly a mitochondrial disorder.

Created: 11 Jan 2022, 3:40 p.m. | Last Modified: 11 Jan 2022, 5:13 p.m.

Panel Version: 2.84

Red List (low evidence)

The protein localises to the mitochondria of renal cells, belongs to a family of X-pro-aminopeptidases, and has a role in ciliary function. Even though the enzyme is expressed in the mitochondria the function and condition (nephronophthisis-like nephropathy) associated with this gene do not truly represent a mitochondrial disorder.

Created: 19 Mar 2020, 10:25 a.m. | Last Modified: 19 Mar 2020, 10:25 a.m.

Panel Version: 2.5

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephronophthisis-like nephropathy 1, MIM#613159

Publications

• 20179356

Comment on list classification: Mutations in this gene were reported in 2 consanguineous families from different ethnicities (Northern Finland and Turkey) with nephronophthisis-like nephropathy. This is a possible DD gene.

Created: 26 Feb 2016, 11:58 a.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal