Unexplained young onset end-stage renal disease - additional genes

Gene: FAN1

Green List (high evidence)

This gene has been added to this panel with green rating as it was present in R257 Unexplained young onset end-stage renal disease panel (v5.1) with the same rating before it was made a super panel.

Created: 25 Sep 2024, 9:36 p.m. | Last Modified: 25 Sep 2024, 9:36 p.m.

Panel Version: 0.65

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Green List (high evidence)

Fan1 knockout mouse model studies showed that the phenotype of these mice is orthologous to the human DNA damage syndrome, karyomegalic interstitial nephritis (KIN). Inactivation of Fan1 in kidney proximal tubule cells sensitized the kidneys to genotoxic and obstructive injury characterized by replication stress and persistent DNA damage response activity.

Created: 30 Nov 2022, 8:47 p.m. | Last Modified: 30 Nov 2022, 8:47 p.m.

Panel Version: 2.1

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
interstitial nephritis; chronic kidney disease; Interstitial nephritis, karyomegalic 614817

Publications

• 35931300

Green List (high evidence)

Mouse model data added by reviewer Yu Leng Phua provides functional data to support this gene-disease association from PMID: 35931300 Airik et al 2022.

Created: 29 May 2023, 10:12 p.m. | Last Modified: 29 May 2023, 10:12 p.m.

Panel Version: 3.1

Comment on list classification: Sufficient cases to rate green for association with a relevant disease and presentation can be in young adults.

Created: 8 Nov 2019, 12:58 p.m. | Last Modified: 8 Nov 2019, 12:58 p.m.

Panel Version: 0.53

This gene was added to the 100,000 genomes project ' Unexplained kidney failure in young people' panel at the suggestion of external reviewer John Sayer.

FAN1 associated with Interstitial nephritis, karyomegalic #614817 (AR) in OMIM. PMID: 22772369 - Zhou et al 2012 - 9 unrelated families with karyomegalic interstitial nephritis which can result in Chronic kidney disease. They identified 12 different homozygous or compound heterozygous mutations in the FAN1 gene. Eight of the 12 mutations resulted in a truncated protein. (Summary from OMIM). End-stage kidney failure ensued by a median age of 45 years in the 12 individuals with KIN and FAN1 mutations. Sufficient cases with likely disease causing mutations to rate this gene green.
Sources: Expert Review

Created: 8 Nov 2019, 12:57 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
interstitial nephritis; chronic kidney disease; Interstitial nephritis, karyomegalic 614817

Publications

• 22772369