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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SLC34A1
solute carrier family 34 member 1
Chromosome 5 Β· 5q35.3
NCBI Gene: 6569Ensembl: ENSG00000131183.12HGNC: HGNC:11019UniProt: Q06495
62PubMed Papers
23Diseases
0Drugs
55Pathogenic Variants
FUNCTIONAL ROLE
Transporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
response to cadmium ionphosphate ion homeostasisprotein bindingsodium:phosphate symporter activityhypercalcemia, infantile, 2hypophosphatemic nephrolithiasis/osteoporosis 1Fanconi renotubular syndrome 2Autosomal recessive infantile hypercalcemia
✦AI Summary

SLC34A1 encodes the renal sodium-phosphate cotransporter 2A (NaPi-IIa), which plays a critical role in maintaining phosphate homeostasis through active phosphate transport in proximal tubule cells 1. The transporter is located in the brush border membrane and mediates sodium-dependent phosphate reabsorption with a Na+:Pi stoichiometry of 3:1 2. Loss-of-function mutations in SLC34A1 cause primary renal phosphate wasting, leading to inappropriate production of 1,25-(OH)2D3 and subsequent symptomatic hypercalcemia characteristic of idiopathic infantile hypercalcemia (IIH) 1. Both biallelic and monoallelic pathogenic variants can cause disease, with patients presenting hypercalcemia, hypercalciuria, nephrocalcinosis, and hypophosphatemia 3. Clinical manifestations vary with onset age, and hypercalcemia may not necessarily present after infancy 3. SLC34A1 variants are significantly enriched in adult kidney stone formers, with monoallelic carriers comprising 8.1% of unselected patients 4. Common genetic variants near SLC34A1 are associated with increased kidney stone disease risk through decreased serum phosphate concentrations 5. Early genetic testing and differentiation from other causes of IIH is critical for targeted phosphate supplementation therapy 1.

Sources cited
1
SLC34A1 encodes NaPi-IIa transporter and mutations cause renal phosphate wasting leading to IIH
PMID: 26047794
2
Transporter located in brush border membrane with 3:1 Na+:Pi stoichiometry
PMID: 40357590
3
Both biallelic and monoallelic variants cause disease with hypercalcemia, hypercalciuria, and nephrocalcinosis
PMID: 38504242
4
SLC34A1 variants enriched in adult kidney stone formers (8.1% monoallelic carriers)
PMID: 38544324
5
Common variants near SLC34A1 associated with kidney stone disease risk through decreased serum phosphate
PMID: 40372791
Disease Associationsβ“˜23
hypercalcemia, infantile, 2Open Targets
0.78Strong
hypophosphatemic nephrolithiasis/osteoporosis 1Open Targets
0.76Strong
Fanconi renotubular syndrome 2Open Targets
0.69Moderate
Autosomal recessive infantile hypercalcemiaOpen Targets
0.52Moderate
nephrolithiasisOpen Targets
0.48Moderate
nephrolithiasis/osteoporosis, hypophosphatemicOpen Targets
0.40Moderate
nephrocalcinosisOpen Targets
0.38Weak
Fanconi renotubular syndrome 1Open Targets
0.38Weak
primary Fanconi syndromeOpen Targets
0.38Weak
hereditary hypophosphatemic rickets with hypercalciuriaOpen Targets
0.38Weak
hypophosphatemiaOpen Targets
0.38Weak
hypercalcemia, infantileOpen Targets
0.37Weak
renal tubular transport diseaseOpen Targets
0.37Weak
chronic kidney diseaseOpen Targets
0.32Weak
kidney failureOpen Targets
0.27Weak
osteogenesis imperfecta type 3Open Targets
0.27Weak
urolithiasisOpen Targets
0.24Weak
autoimmune diseaseOpen Targets
0.20Weak
genetic disorderOpen Targets
0.19Weak
bronchiectasis with or without elevated sweat chloride 2Open Targets
0.12Weak
Fanconi renotubular syndrome 2UniProt
Hypercalcemia, infantile, 2UniProt
Nephrolithiasis/osteoporosis, hypophosphatemic, 1UniProt
Pathogenic Variants55
NM_003052.5(SLC34A1):c.644+1G>APathogenic
Hypercalcemia, infantile, 2|Nephrolithiasis;Nephrocalcinosis|not provided|SLC34A1-related disorder|Hypercalcemia, infantile, 2;Fanconi renotubular syndrome 2;Hypophosphatemic nephrolithiasis/osteoporosis 1
β˜…β˜…β˜†β˜†2025
NM_003052.5(SLC34A1):c.189_190del (p.Cys64fs)Pathogenic
Fanconi renotubular syndrome 2;Hypophosphatemic nephrolithiasis/osteoporosis 1;Hypercalcemia, infantile, 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 64
NM_003052.5(SLC34A1):c.454_480dup (p.Val152_Val160dup)Pathogenic
Hypercalcemia, infantile, 2|not provided|Hypophosphatemic nephrolithiasis/osteoporosis 1;Hypercalcemia, infantile, 2;Fanconi renotubular syndrome 2
β˜…β˜…β˜†β˜†2025β†’ Residue 152
NM_003052.5(SLC34A1):c.1484G>A (p.Arg495His)Likely pathogenic
not provided|Hypophosphatemic nephrolithiasis/osteoporosis 1;Fanconi renotubular syndrome 2;Hypercalcemia, infantile, 2
β˜…β˜…β˜†β˜†2025β†’ Residue 495
NM_003052.5(SLC34A1):c.458G>T (p.Gly153Val)Likely pathogenic
Hypercalcemia, infantile, 2|SLC34A1-related disorder|Hypercalcemia, infantile, 2;Fanconi renotubular syndrome 2;Hypophosphatemic nephrolithiasis/osteoporosis 1|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 153
NM_003052.5(SLC34A1):c.1006+1G>APathogenic
Hypercalcemia, infantile, 2|not provided|SLC34A1-related disorder
β˜…β˜…β˜†β˜†2025
NM_003052.5(SLC34A1):c.241dup (p.Glu81fs)Pathogenic
not provided|Hypercalcemia, infantile, 2|Hypophosphatemic nephrolithiasis/osteoporosis 1;Hypercalcemia, infantile, 2;Fanconi renotubular syndrome 2
β˜…β˜…β˜†β˜†2025β†’ Residue 81
NM_003052.5(SLC34A1):c.1007-1G>ALikely pathogenic
not provided
β˜…β˜…β˜†β˜†2025
NM_003052.5(SLC34A1):c.527_528del (p.Ser176fs)Pathogenic
Hypercalcemia, infantile, 2|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 176
NM_003052.5(SLC34A1):c.73C>T (p.Arg25Ter)Pathogenic
not provided|Fanconi renotubular syndrome 2;Hypophosphatemic nephrolithiasis/osteoporosis 1;Hypercalcemia, infantile, 2|Hypophosphatemic nephrolithiasis/osteoporosis 1
β˜…β˜…β˜†β˜†2024β†’ Residue 25
NM_003052.5(SLC34A1):c.745C>T (p.Arg249Ter)Pathogenic
Autosomal recessive infantile hypercalcemia|Hypercalcemia, infantile, 2;Hypophosphatemic nephrolithiasis/osteoporosis 1;Fanconi renotubular syndrome 2|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 249
NM_003052.5(SLC34A1):c.690dup (p.Val231fs)Pathogenic
Fanconi renotubular syndrome 2|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 231
NM_003052.5(SLC34A1):c.684G>A (p.Trp228Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 228
NM_003052.5(SLC34A1):c.1739C>T (p.Pro580Leu)Likely pathogenic
Fanconi renotubular syndrome 2;Hypercalcemia, infantile, 2;Hypophosphatemic nephrolithiasis/osteoporosis 1
β˜…β˜†β˜†β˜†2025β†’ Residue 580
NM_003052.5(SLC34A1):c.1879del (p.Arg627fs)Likely pathogenic
Fanconi renotubular syndrome 2;Hypercalcemia, infantile, 2;Hypophosphatemic nephrolithiasis/osteoporosis 1
β˜…β˜†β˜†β˜†2025β†’ Residue 627
NM_003052.5(SLC34A1):c.19_20del (p.Arg7fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 7
NM_003052.5(SLC34A1):c.782_810del (p.Arg261fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 261
NM_003052.5(SLC34A1):c.1687_1688del (p.Arg564fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 564
NM_003052.5(SLC34A1):c.1174+1G>ALikely pathogenic
Hypophosphatemic nephrolithiasis/osteoporosis 1;Hypercalcemia, infantile, 2;Fanconi renotubular syndrome 2
β˜…β˜†β˜†β˜†2025
NM_003052.5(SLC34A1):c.1271C>A (p.Ser424Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 424
View on ClinVar β†—
Related Genes
SLC9A3Protein interaction98%NHERF1Protein interaction98%PDZK1Protein interaction94%PHEXProtein interaction85%SLC17A4Protein interaction82%FGF23Protein interaction80%
Tissue Expression6 tissues
Liver
100%
Bone Marrow
22%
Lung
1%
Brain
0%
Heart
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
SLC34A1SLC9A3NHERF1PDZK1PHEXSLC17A4FGF23
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q06495
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
1.29LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.04 [0.84–1.29]
RankingsWhere SLC34A1 stands among ~20K protein-coding genes
  • #7,510of 20,598
    Most Researched62
  • #1,244of 5,498
    Most Pathogenic Variants55 Β· top quartile
  • #13,567of 17,882
    Most Constrained (LOEUF)1.29
Genes detectedSLC34A1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia.
PMID: 26047794
J Am Soc Nephrol Β· 2016
1.00
2
Role of Genetic Testing in Kidney Stone Disease: A Narrative Review.
PMID: 39096463
Curr Urol Rep Β· 2024
0.90
3
Prevalence and characteristics of genetic disease in adult kidney stone formers.
PMID: 38544324
Nephrol Dial Transplant Β· 2024
0.80
4
Biallelic and monoallelic pathogenic variants in CYP24A1 and SLC34A1 genes cause idiopathic infantile hypercalcemia.
PMID: 38504242
Orphanet J Rare Dis Β· 2024
0.70
5
Genetic variants predisposing to an increased risk of kidney stone disease.
PMID: 40372791
J Clin Invest Β· 2025
0.60