Renal tubulopathies

Gene: SLC9A3R1

Green List (high evidence)

Added new-gene-name tag, new approved HGNC gene symbol for SLC9A3R1 (HGNC:11075) is NHERF1.

Created: 8 Feb 2023, 1:52 p.m. | Last Modified: 8 Feb 2023, 1:52 p.m.

Panel Version: 3.3

Comment on list classification: After consultation with the Genomics England rare disease clinical team leaving this gene red on this panel as hypophosphatemia is covered by the 'R154 Hypophosphataemia or rickets' panel where it is rated amber.

Created: 5 Sep 2019, 10:24 p.m. | Last Modified: 5 Sep 2019, 10:24 p.m.

Panel Version: 1.174

Associated with Nephrolithiasis/osteoporosis, hypophosphatemic, 2 #612287 in OMIM.

PubMed: 18784102 - Karim et al 2008 - sequenced the NHERF1 gene (now called SLC9A3R1) in 158 patients, 94 of whom had either nephrolithiasis or bone demineralization. They identified three distinct heterozygous missense mutations (328C->G, L110V; 458G->A,R153Q;673G->A,E225K) in the NHERF1 gene in four unrelated patients. All four patients with NHERF1 mutations had TmP/GFR values below the lower limit of the normal range, as well as hypophosphatemia. Patients 1, 3, and 4 also had recurrent nephrolithiasis. The four patients with mutations did not have proximal-tubule dysfunction other than the low TmP/GFR value. The results identify NHERF1 mutations as a cause of renal phosphate loss that may increase the risk of renal stone formation or bone demineralization: the mutations were identified only in patients with TmP/GFR values that were below normal and significantly lower than those in patients in whom mutations were not identified

PMID: 25296721 - Halbritter et al 2015 - identify pathogenic heterozygous variants in SLC9A3R1 in 2 families. c.673G>A, p.Glu225Lys and c.888+2T>C, 5′ splice site (new variant).

PMID: 19073985 - Bergwitz et al 2008 - report that 2 of the variants (328C->G and 458G->A) reported by Karim et al 2008 are listed as single-nucleotide polymorphisms in the National Center for Biotechnology Information dbSNP, Ensembl, and GeneCards databases with an allele frequency of 0.01 and 0.03.

Amber rating suggested.

Created: 2 Sep 2019, 8:59 p.m. | Last Modified: 5 Sep 2019, 10:23 p.m.

Panel Version: 1.173

This gene was part of an initial gene list collated by Emma Ashton (NE Thames Regional Genetics laboratory, GOSH NHS Foundation Trust) January 2019 on behalf of the GMS Renal Specialist Test Group; Gene Symbol submitted: SLC9A3R1; Suggested initial gene rating: green; Evidence for inclusion: none provided; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none provided

Created: 3 Feb 2019, 11:32 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Nephrolithiasis/osteoporosis, hypophosphatemic, 2, MIM 612287

Variants in this GENE are reported as part of current diagnostic practice