Proteinuric renal disease

Gene: KIRREL1

I don't know

Comment on list classification: Promoting this gene from grey to amber. 2 cases plus some limited functional data.

Created: 13 Jan 2021, 9:30 p.m. | Last Modified: 13 Jan 2021, 9:30 p.m.

Panel Version: 2.41

PMID: 31472902 - Solanki et al 2019 - using WES and targeted exon sequencing they identified two homozygous missense variants (c.1318C>T, p.Arg440Cys and c.1718C>T, p.Ser573Leu) in KIRREL1 gene in two individuals with steroid-resistant nephrotic syndrome from unrelated consanguineous families. The variants are reported to have minor allele frequencies in gnomAD of 3.97×10−6 for p.Arg440Cys and MAF of 7.87×10−4 for p.Ser573Leu. However, the p.Ser573Leu variant, which was found in a child of Italian descent, is found in homozygous state in one control subject in GnomAD and has an allele frequency of 0.0011 in European populations. Functional studies showed using podocytes transfected with cDNAs containing the variants from the patients showed that mutant KIRREL1 proteins failed to localize to the podocyte cell membrane, indicating defective trafficking and impaired podocytes function

Created: 13 Jan 2021, 9:29 p.m. | Last Modified: 13 Jan 2021, 9:29 p.m.

Panel Version: 2.39

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
steroid-resistant nephrotic syndrome MONDO:0044765

Publications

• 31472902

I don't know

Two unrelated families reported with bi-allelic variants and limited functional data.
Sources: Literature

Created: 3 Nov 2020, 11:20 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Steroid-resistant nephrotic syndrome

Publications

• 31472902