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 apical plasma membrane. Implicated in several diseases, including Fanconi syndrome (multiple); hereditary hypophosphatemic rickets with hypercalciuria; hypophosphatemic nephrolithiasis/osteoporosis 1; infantile hypercalcemia 2; and nephrolithiasis. [provided by Alliance of Genome Resources, Jun 2026]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNephrolithiasis/osteoporosis, hypophosphatemic, 1

UniProtFanconi renotubular syndrome 2

UniProtHypercalcemia, infantile, 2

Clinical highlights

Gene–disease validity (ClinGen)

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.83

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in SLC34A1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 75

873 rare PASS variants

Rare truncating (LoF)

1 in 640

150 rare PASS variants

Rare synonymous (reference)

1 in 120

404 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC34A1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 94	1 in 680
South Asian	~43k	1 in 33	1 in 350
Remaining (unassigned)	~30k	1 in 63	1 in 790
European (Finnish)	~27k	1 in 190	1 in 2,400
Admixed American	~22k	1 in 55	1 in 1,200
African / African American	~21k	1 in 39	1 in 530
East Asian	~20k	1 in 85	1 in 570
Ashkenazi Jewish	~13k	1 in 230	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 59	1 in 290

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓