SLC34A3

Chr 9AR

solute carrier family 34 member 3

Also known as: HHRH, NPT2C, NPTIIc

NCBI Gene: 142680ENSG00000198569UniProt: Q8N130OMIM: 609826

This gene encodes a sodium-phosphate cotransporter that actively transports phosphate into renal tubular cells via the brush border membrane, maintaining kidney phosphate homeostasis. Mutations cause hypophosphatemic rickets with hypercalciuria, inherited in an autosomal recessive pattern. The gene shows low constraint to loss-of-function variation, consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 1.371 OMIM phenotype
Clinical Summary— SLC34A3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
64 unique Pathogenic / Likely Pathogenic· 147 VUS of 300 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
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
-1.29Z-score
OE missense 1.18 (1.10–1.28)
466 obs / 393.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.95 (0.67–1.37)
0≤0.351.4
Missense OE1.18 (1.10–1.28)
0≤0.61.4
Synonymous OE1.30
0≤1.21.6
LoF obs/exp: 21 / 22.1Missense obs/exp: 466 / 393.8Syn Z: -3.27
DN
0.76top 25%
GOF
0.74top 25%
LOF
0.3357th %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
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.

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

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic27
VUS147
Likely Benign72
Benign2
Conflicting7
37
Pathogenic
27
Likely Pathogenic
147
VUS
72
Likely Benign
2
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
1
30
0
37
Likely Pathogenic
20
1
5
1
27
VUS
2
124
16
5
147
Likely Benign
0
4
32
36
72
Benign
0
0
0
2
2
Conflicting
—7
Total281308344292

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients