SLC34A1
Chr 5ARADsolute carrier family 34 member 1
Also known as: FRTS2, HCINF2, NAPI-3, NPHLOP1, NPT2, NPTIIa, SLC11, SLC17A2
The SLC34A1 protein is a sodium-phosphate cotransporter that actively transports phosphate into renal tubular cells with a 3:1 Na+:phosphate stoichiometry. Mutations cause autosomal recessive Fanconi renotubular syndrome, autosomal dominant infantile hypercalcemia, and hypophosphatemic nephrolithiasis with osteoporosis, affecting phosphate homeostasis and kidney function. The gene shows low constraint against loss-of-function variants (high LOEUF of 1.828), consistent with its association with both recessive and dominant inheritance patterns.
Primary Disease Associations & Inheritance
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
500 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 12 | 0 | 22 | 0 | 34 |
Likely Pathogenic | 18 | 4 | 7 | 0 | 29 |
VUS | 7 | 219 | 23 | 2 | 251 |
Likely Benign | 0 | 3 | 60 | 87 | 150 |
Benign | 0 | 0 | 12 | 1 | 13 |
Conflicting | — | 20 | |||
| Total | 37 | 226 | 124 | 90 | 497 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLC34A1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools