SLC34A3

Chr 9AR

solute carrier family 34 member 3

Also known as: HHRH, NPT2C, NPTIIc

NCBI Gene: 142680ENSG00000198569UniProt: Q8N130

This gene encodes a member of SLC34A transporter family of proteins, and is expressed primarily in the kidney. It is involved in transporting phosphate into cells via sodium cotransport in the renal brush border membrane, and contributes to the maintenance of inorganic phosphate concentration in the kidney. Mutations in this gene are associated with hereditary hypophosphatemic rickets with hypercalciuria. Alternatively spliced transcript variants varying in the 5' UTR have been found for this gene.[provided by RefSeq, Apr 2010]

Primary Disease Associations & Inheritance

Hypophosphatemic rickets with hypercalciuriaMIM #241530
AR
UniProtHereditary hypophosphatemic rickets with hypercalciuria
987
ClinVar variants
103
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC34A3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
103 Pathogenic / Likely Pathogenic· 257 VUS of 987 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.37LOEUF
pLI 0.000
Z-score 0.22
OE 0.95 (0.67–1.37)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.29Z-score
OE missense 1.18 (1.10–1.28)
466 obs / 393.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.95 (0.67–1.37)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.18 (1.10–1.28)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.30
0≤1.21.6
LoF obs/exp: 21 / 22.1Missense obs/exp: 466 / 393.8Syn Z: -3.27

ClinVar Variant Classifications

987 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic43
VUS257
Likely Benign202
Benign9
Conflicting21
60
Pathogenic
43
Likely Pathogenic
257
VUS
202
Likely Benign
9
Benign
21
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
10
0
50
0
60
Likely Pathogenic
28
5
9
1
43
VUS
5
220
24
8
257
Likely Benign
0
4
113
85
202
Benign
0
1
7
1
9
Conflicting
—21
Total4323020395592

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC34A3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hypophosphatemic rickets with hypercalciuria

MIM #241530

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Presentation and outcome in carriers of pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter NPT 2a and 2c.
Brunkhorst M et al.·Kidney Int
2025
Mutations in SLC34A3/NPT2c are associated with kidney stones and nephrocalcinosis.
Dasgupta D et al.·J Am Soc Nephrol
2014Case report
Uncovering genetic causes of hypophosphatemia.
Puente-Ruiz N et al.·J Intern Med
2023Review
Effects of SLC34A3 or SLC34A1 variants on calcium and phosphorus homeostasis.
Naciri Bennani H et al.·Pediatr Nephrol
2025
Relationship between clinical phenotype and in vitro analysis of 13 NPT2c/SCL34A3 mutants.
Brazier F et al.·Sci Rep
2023
Novel heterozygous GATA3 and SLC34A3 variants in a 6-year-old boy with Barakat syndrome and hypercalciuria.
Yu S et al.·Mol Genet Genomic Med
2020Case report
An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH).
Zhu Z et al.·Kidney Int
2024Cohort
[Updates on rickets and osteomalacia: the role of NaPi-2c/SLC34A3 and hypophosphataemic rickets].
Segawa H et al.·Clin Calcium
2013Review
Clinical and Molecular Genetic Characteristics of Patients with Hereditary Hypophosphatemia.
Eltan M et al.·J Clin Endocrinol Metab
2025Cohort
Inherited non-FGF23-mediated phosphaturic disorders: A kidney-centric review.
Walker E et al.·Best Pract Res Clin Endocrinol Metab
2024Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools