SLC34A1

Chr 5

solute carrier family 34 member 1

Also known as: FRTS2, HCINF2, NAPI-3, NPHLOP1, NPT2, NPTIIa, SLC11, SLC17A2

NCBI Gene: 6569 ENSG00000131183 UniProt: Q06495

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.

ResearchSummary from RefSeq, OMIM, UniProt

Enables sodium:phosphate symporter activity. Involved in several processes, including phosphate ion homeostasis; response to cadmium ion; and response to lead ion. Located in several cellular components, including apical plasma membrane; mitotic spindle; and nuclear speck. Implicated in several diseases, including Fanconi syndrome (multiple); chronic kidney disease; hereditary hypophosphatemic rickets with hypercalciuria; hypophosphatemic nephrolithiasis/osteoporosis 1; and nephrolithiasis. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.83

Clinical Summary— SLC34A1

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Gene-Disease Validity (ClinGen)

hypercalcemia, infantile, 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

59 unique Pathogenic / Likely Pathogenic· 282 VUS of 581 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.83LOEUF

pLI 0.000

Z-score -1.85

OE 1.41 (1.07–1.83)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.48Z-score

OE missense 1.07 (0.98–1.16)

400 obs / 374.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.41 (1.07–1.83)

0≤0.351.4

Missense OE?1.07 (0.98–1.16)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 34 / 24.2Missense obs/exp: 400 / 374.1Syn Z: -0.24

This gene — mechanism propensity

0.76top 25%

GOF

0.73top 25%

LOF

0.3746th %ile

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.

DNprediction above median · 1 literature citation

GOFprediction above median

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

DNThese results indicate that the mutant proteins altered the function of the wild-type NPT2a through a dominant negative effect.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

1.PMID 12324554 ↗

ClinVar Variant Classifications

581 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25

Likely Pathogenic34

VUS282

Likely Benign174

Benign23

Conflicting40

Pathogenic

Likely Pathogenic

282

VUS

174

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	19	4	2	0	25
Likely Pathogenic	27	7	0	0	34
VUS	9	239	28	6	282
Likely Benign	0	7	66	101	174
Benign	0	1	19	3	23
Conflicting	—				40
Total	55	258	115	110	578

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

58 pathogenic / likely-pathogenic (of 70) ClinVar copy-number / structural variants overlap SLC34A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →