Rare multisystem ciliopathy disorders

Gene: XPNPEP3

Green List (high evidence)

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).
Feedback from Helen Brittain (GEL Clinical Fellow): this gene is suitable for this panel.

Created: 17 Feb 2022, 1:27 p.m. | Last Modified: 17 Feb 2022, 1:27 p.m.

Panel Version: 1.157

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review, however, reviewers on the Primary ciliary disorders (https://panelapp.genomicsengland.co.uk/panels/178/gene/XPNPEP3/#!review) question the relevance of the phenotype associated with variants in XPNPEP3. Helen Brittain (GEL Clinical Fellow) has been consulted regarding this issue.

Created: 11 Jan 2022, 5:23 p.m. | Last Modified: 11 Jan 2022, 5:23 p.m.

Panel Version: 1.156

Red List (low evidence)

Mutations only identified in 2 families. Not offered on GOS ciliopathy panel. Possible DD on G2P

Created: 19 Jan 2017, 3:44 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephronophthisis-like nephropathy 1 613159

Publications

• 20179356