SLC17A3

Chr 6AD

solute carrier family 17 member 3

Also known as: GOUT4, NPT4, UAQTL4

NCBI Gene: 10786ENSG00000124564UniProt: O00476

The protein encoded by this gene is a voltage-driven transporter that excretes intracellular urate and organic anions from the blood into renal tubule cells. Two transcript variants encoding different isoforms have been found for this gene. The longer isoform is a plasma membrane protein with transporter activity while the shorter isoform localizes to the endoplasmic reticulum. [provided by RefSeq, Aug 2012]

Primary Disease Associations & Inheritance

[Uric acid concentration, serum, QTL4]MIM #612671
AD
{Gout susceptibility 4}MIM #612671
AD
68
ClinVar variants
5
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC17A3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 57 VUS of 68 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.
1.48LOEUF
pLI 0.000
Z-score -0.49
OE 1.10 (0.82–1.48)
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.
-0.30Z-score
OE missense 1.05 (0.95–1.16)
272 obs / 258.5 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.1.10 (0.82–1.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.95–1.16)
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.1.01
0≤1.21.6
LoF obs/exp: 31 / 28.2Missense obs/exp: 272 / 258.5Syn Z: -0.05

ClinVar Variant Classifications

68 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS57
Likely Benign2
Benign4
4
Pathogenic
1
Likely Pathogenic
57
VUS
2
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
1
50
6
0
57
Likely Benign
0
2
0
0
2
Benign
0
2
0
2
4
Total15411268

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC17A3 · 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

[Uric acid concentration, serum, QTL4]

MIM #612671

Molecular basis of disorder known

Autosomal dominant

{Gout susceptibility 4}

MIM #612671

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The homocysteine associated variant rs548987 of SLC17A3 confers susceptibility to ischemic stroke in Chinese population.
Huang S et al.·J Neurol Sci
2016
Linkage analysis using whole exome sequencing data implicates SLC17A1, SLC17A3, TATDN2 and TMEM131L in type 1 diabetes in Kuwaiti families.
Hebbar P et al.·Sci Rep
2023
Differences of Uric Acid Transporters Carrying Extracellular Vesicles in the Urine from Uric Acid and Calcium Stone Formers and Non-Stone Formers.
Lin Z et al.·Int J Mol Sci
2022
Effect of genetic variants associated with plasma homocysteine levels on stroke risk.
Cotlarciuc I et al.·Stroke
2014
Molecular Patterns Discriminate Accommodation and Subclinical Antibody-mediated Rejection in Kidney Transplantation.
Hruba P et al.·Transplantation
2019
Functional analysis of human sodium-phosphate transporter 4 (NPT4/SLC17A3) polymorphisms.
Jutabha P et al.·J Pharmacol Sci
2011Functional
Association of rare and common genetic variants in MOCOS with inadequate response to allopurinol.
Fanning NC et al.·Rheumatology (Oxford)
2024
Identification of six novel susceptibility loci for dyslipidemia using longitudinal exome-wide association studies in a Japanese population.
Yasukochi Y et al.·Genomics
2019Natural history
Common polymorphisms influencing serum uric acid levels contribute to susceptibility to gout, but not to coronary artery disease.
Stark K et al.·PLoS One
2009
Serum and cerebrospinal fluid uric acid levels in lewy body disorders: associations with disease occurrence and amyloid-β pathway.
Maetzler W et al.·J Alzheimers Dis
2011
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