Primary ciliary disorders

Gene: XPNPEP3

I don't know

Helen Brittain (GEL Clinical Fellow) agrees with the review from Ian Berry (below) that this gene is not relevant for Primary ciliary disorders. XPNPEP3 is recommended to be green on Renal ciliopathies (https://panelapp.genomicsengland.co.uk/panels/725/gene/XPNPEP3/#!review)

Created: 1 Apr 2022, 9:03 a.m. | Last Modified: 1 Apr 2022, 9:03 a.m.

Panel Version: 1.40

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review, however, the reviewers 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, 5:21 p.m. | Last Modified: 11 Jan 2022, 5:21 p.m.

Panel Version: 1.40

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, 5:18 p.m. | Last Modified: 11 Jan 2022, 5:18 p.m.

Panel Version: 1.39

Red List (low evidence)

Gene should be deleted - causes a primary ciliopathy;PCD is a motile ciliopathy, likely unrelated at a functional level.

Created: 8 Dec 2015, 5:33 p.m.

Phenotypes
ciliopathies

This is a ciliopathy but not a Primary Ciliary Disorder gene and should be removed from the panel

Created: 8 Dec 2015, 4:25 p.m.

Phenotypes
ciliopathies