SLC22A12

Chr 11AR

solute carrier family 22 member 12

Also known as: OAT4L, RST, UAT, URAT1, hURAT1

NCBI Gene: 116085ENSG00000197891UniProt: Q96S37

The protein encoded by this gene is a member of the organic anion transporter (OAT) family, and it acts as a urate transporter to regulate urate levels in blood. This protein is an integral membrane protein primarily found in epithelial cells of the proximal tubule of the kidney. An elevated level of serum urate, hyperuricemia, is associated with increased incidences of gout, and mutations in this gene cause renal hypouricemia type 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

Primary Disease Associations & Inheritance

Hypouricemia, renalMIM #220150
AR
UniProtHypouricemia renal 1
347
ClinVar variants
31
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— SLC22A12
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 177 VUS of 347 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
1.30LOEUF
pLI 0.000
Z-score 0.44
OE 0.90 (0.64–1.30)
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.
0.37Z-score
OE missense 0.94 (0.86–1.03)
315 obs / 334.2 exp
Tolerant

Mild missense constraint

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.0.90 (0.64–1.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.86–1.03)
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.1.09
0≤1.21.6
LoF obs/exp: 21 / 23.3Missense obs/exp: 315 / 334.2Syn Z: -0.90

ClinVar Variant Classifications

347 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
Likely Pathogenic14
VUS177
Likely Benign74
Benign42
Conflicting21
17
Pathogenic
14
Likely Pathogenic
177
VUS
74
Likely Benign
42
Benign
21
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
6
9
0
17
Likely Pathogenic
6
4
4
0
14
VUS
1
143
25
8
177
Likely Benign
0
3
33
38
74
Benign
0
0
34
8
42
Conflicting
—21
Total915610554345

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC22A12 · 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

Hypouricemia, renal

MIM #220150

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The genetics of hyperuricaemia and gout.
Reginato AM et al.·Nat Rev Rheumatol
2012Review
Pathogenic Variants of SLC22A12 (URAT1) and SLC2A9 (GLUT9) in Spanish Patients with Renal Hypouricemia: Founder Effect of SLC2A9 Variant c.374C>T; p.(T125M).
Perdomo-Ramirez A et al.·Int J Mol Sci
2023Cohort
Metabolic crosstalk and therapeutic interplay between diabetes and hyperuricemia.
Yang T et al.·Diabetes Res Clin Pract
2025Review
New SLC22A12 (URAT1) Variant Associated with Renal Hypouricemia Identified by Whole-Exome Sequencing Analysis and Bioinformatics Predictions.
Perdomo-Ramírez A et al.·Genes (Basel)
2023Case report
Contribution of SLC22A12 on hypouricemia and its clinical significance for screening purposes.
Cha DH et al.·Sci Rep
2019
Genotype and Phenotype of Renal Hypouricemia: A Single-Center Study from China.
Mou L et al.·Mol Diagn Ther
2024
A review on gout: Looking back and looking ahead.
Tao H et al.·Int Immunopharmacol
2023Review
Differential gene expression of ABCG2, SLC22A12, IL-1β, and ALPK1 in peripheral blood leukocytes of primary gout patients with hyperuricemia and their comorbidities: a case-control study.
Natsuko PD et al.·Eur J Med Res
2022Cohort
Polymorphisms in GCKR, SLC17A1 and SLC22A12 were associated with phenotype gout in Han Chinese males: a case-control study.
Zhou ZW et al.·BMC Med Genet
2015
URAT1 and GLUT9 mutations in Spanish patients with renal hypouricemia.
Claverie-Martin F et al.·Clin Chim Acta
2018Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Additive Association of ABCG2 rs4148155 and SLC22A12 rs75786299 Polymorphisms with Hyperuricemia, Gout, and Nephrolithiasis: A Hospital-Based, Case-Control Study.
Lin CT et al.·Kidney Dis (Basel)
2026🔓 Open Access
Association of single-nucleotide polymorphisms in SLC2A9, SLC22A12 and SLC22A11 genes with hyperuricemia in the Chinese Tibetan population.
Li RX et al.·Medicine (Baltimore)
2025🔓 Open Access
Gene-environment interaction modifies the association between hyperinsulinemia and serum urate levels through SLC22A12.
Fujii W et al.·J Clin Invest
2025🔓 Open Access
Benzbromarone Analog SAR: Potent hURAT1 (SLC22A12) Inhibitors and Drug Transporter Interaction Studies.
Jutabha P et al.·Drug Des Devel Ther
2025🔓 Open Access
A case of renal hypouricemia due to T217M mutation in SLC22A12 incidentally associated with IgA nephropathy.
Sakurabu Y et al.·Clin Case Rep
2024🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
AMPD3, OMIM*102772, AMP Deaminase DeficiencyAK1, OMIM *103000, Adenylate Kinase DeficiencyAMPD1, OMIM *102770, Myopathy Due to Myoadenylate Deaminase Deficiency

A Natural History Study Seeks to Understand the Clinical, Genomic, Pharmacological, Laboratory, and Dietary Determinates of Pyrimidine and Purine Metabolism Disorders

RECRUITING
NCT06092346National Human Genome Research Institute (NHGRI)Started 2023-12-19

External Resources

Links to major genomics databases and tools