Mitochondrial disorders
Gene: XPNPEP3
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
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
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
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.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Tag Q2_21_rating was removed from gene: XPNPEP3. Tag Q2_21_phenotype was removed from gene: XPNPEP3. Tag Q2_21_expert_review was removed from gene: XPNPEP3.
Tag Q1_22_rating was removed from gene: XPNPEP3. Tag Q2_21_rating tag was added to gene: XPNPEP3.
Tag Q2_21_expert_review tag was added to gene: XPNPEP3.
Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Gene: xpnpep3 has been classified as Amber List (Moderate Evidence).
Tag Q2_21_phenotype tag was added to gene: XPNPEP3. Tag Q1_22_rating tag was added to gene: XPNPEP3.
Phenotypes for gene: XPNPEP3 were changed from nephronophthisis-like nephropathy to Nephronophthisis-like nephropathy 1 OMIM:613159; nephronophthisis-like nephropathy 1 MONDO:0013163
Publications for gene: XPNPEP3 were set to 20179356
Publications for gene: XPNPEP3 were set to PMID: 20179356
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Amber List (Moderate Evidence).
XPNPEP3 was created by [email protected]
XPNPEP3 was added to All recognised syndromes and those with suggestive featurespanel. Sources: Expert list