SLC34A1: Sodium-Phosphate Cotransporter 2A (NaPi-IIa) – Key Regulator of Renal Phosphate Homeostasis
Comprehensive genomic and proteomic analysis of SLC34A1, including gene structure, expression, disease associations, and functional classification.
Gene Information Card
| Symbol | SLC34A1 |
|---|---|
| Full Name | Solute Carrier Family 34 Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q35.3 |
| NCBI Gene ID | 6569 ncbi.nlm.nih.gov/gene/6569 |
| Ensembl ID | ENSG00000131183 |
| UniProt ID | Q06495 |
| OMIM ID | 182309 |
| HGNC ID | 11019 |
| Aliases | NaPi-IIa, NPT2a, NPT2, SLC11A4 |
Description
SLC34A1 encodes the sodium-dependent phosphate cotransporter 2A (NaPi-IIa), primarily expressed in the renal proximal tubule. It mediates the reabsorption of inorganic phosphate from the glomerular filtrate, playing a critical role in phosphate homeostasis. Mutations in SLC34A1 are associated with hypophosphatemic nephrolithiasis/osteoporosis type 1 (NPHLOP1) and Fanconi renotubular syndrome type 2 (FRTS2).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypophosphatemic nephrolithiasis/osteoporosis type 1 (NPHLOP1) | Loss-of-function mutations reduce renal phosphate reabsorption, leading to hypophosphatemia, hypercalciuria, and stone formation. | OMIM #612286; ClinVar pathogenic variants |
| Fanconi renotubular syndrome type 2 (FRTS2) | Impaired NaPi-IIa function causes generalized proximal tubular dysfunction, including phosphaturia, aminoaciduria, and glycosuria. | OMIM #613388; multiple case reports |
| Idiopathic hypercalciuria | Altered phosphate transport may secondarily increase 1,25-dihydroxyvitamin D synthesis, enhancing intestinal calcium absorption. | Association studies; functional data |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 68.2 | High |
| Small intestine | 3.1 | Low |
| Liver | 0.8 | Not detected |
| Lung | 0.5 | Not detected |
| Brain | 0.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HK-2 (proximal tubule) | 72.5 | High expression |
| HEK293 | 1.2 | Low expression |
| HepG2 | 0.3 | Not detected |
| A549 | 0.1 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.228C>T (p.Arg76Cys) | Missense | <0.01% | Reduced phosphate transport activity; associated with NPHLOP1 |
| c.575G>A (p.Arg192His) | Missense | <0.01% | Impaired membrane trafficking; FRTS2 |
| c.1003G>A (p.Gly335Arg) | Missense | <0.01% | Loss of function; hypophosphatemia |
| c.1400T>C (p.Leu467Pro) | Missense | <0.01% | Dominant negative effect; severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Most reported missense mutations (e.g., p.Arg76Cys, p.Gly335Arg) reduce or abolish phosphate transport activity, leading to renal phosphate wasting.
Gain of Function (GOF)
No gain-of-function mutations have been documented for SLC34A1.
Dominant Negative (DN)
p.Leu467Pro is proposed to exert a dominant-negative effect by disrupting oligomerization and membrane localization.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Renal phosphate reabsorption (Reactome: R-HSA-427589)
• Vitamin D metabolism and regulation (Reactome: R-HSA-196791)
• SLC-mediated transmembrane transport (Reactome: R-HSA-425407)
Protein Summary
NaPi-IIa is a 639-amino acid integral membrane protein with 8 transmembrane domains. It functions as a sodium-phosphate symporter, coupling the inward sodium gradient to phosphate uptake. The protein is localized to the apical membrane of renal proximal tubule cells and is regulated by dietary phosphate, parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC34A1 Knockout HEK293 Cell Line | EDJ-KQ3902 | Human | 6569 | Details Get a Quote |
| SLC34A1 Knockout HeLa Cell Line | EDJ-KQ54513 | Human | 6569 | Details Get a Quote |
| SLC34A1 Knockout A-549 Cell Line | EDJ-KQ62998 | Human | 6569 | Details Get a Quote |
| SLC34A1 Knockout HCT 116 Cell Line | EDJ-KQ71468 | Human | 6569 | Details Get a Quote |
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