The SLC34A1 gene is located on chromosome 5 at q35.3 and encodes the Solute Carrier Family 34 Member 1.
Multiple disease entities have been reported in association with this gene. Per criteria outlined by the ClinGen Lumping and Splitting Working Group, there was evidence of differences in their molecular mechanism, inheritance pattern and phenotypic spectrum. Therefore, Fanconi renotubular syndrome 2 (OMIM:613388) has been split from the following disease entities, Hypercalcemia, infantile, 2 (OMIM: 616963), and Nephrolithiasis/osteoporosis, hypophosphatemic, 1 (OMIM:612286). The lumped disease entity for autosomal recessive hypercalcemia, infantile, 2 and autosomal dominant nephrolithiasis/osteoporosis, hypophosphatemic, 1 has been curated separately.
SLC34A1 was first reported in relation to autosomal recessive Fanconi renotubular syndrome 2 in 2010 (Magen et al., PMID: 20335586). The mechanism of pathogenicity is reported to be loss of function. Fanconi renotubular syndrome is a renal disorder resulting from decreased solute and water reabsorption in the proximal tubule of the kidney.
Only one variant (in-frame duplication) has been reported in one proband in one publication (PMID: 20335586, included in this curation). A total of 0.5/12 pts. for genetic evidence was reached considering case-level data. There is very little evidence supporting this gene-disease association beyond the expression of SLC34A1 in the brush border of proximal tubule cells in humans (PMID: 8327470). A total of 0.5/6 pts. for experimental evidence was reached.
In summary, the evidence supporting the relationship between SLC34A1 and autosomal recessive Fanconi renotubular syndrome 2 has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role SLC34A1 plays in this disease.
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