SLC22A12

Chr 11AR

solute carrier family 22 member 12

ENSG00000197891 UniProt: Q96S37 OMIM: 607096

This protein functions as an electroneutral antiporter in the proximal tubule of the kidney, translocating urate across the apical membrane in exchange for organic or inorganic anions to maintain blood uric acid levels. Mutations cause autosomal recessive renal hypouricemia type 1, characterized by abnormally low serum uric acid levels due to impaired renal urate reabsorption. The gene shows low constraint to loss-of-function variation (LOEUF 1.299), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Electroneutral antiporter that translocates urate across the apical membrane of proximal tubular cells in exchange for monovalent organic or inorganic anions (PubMed:12024214, PubMed:22194875, PubMed:35144162, PubMed:35462902). Involved in renal reabsorption of urate and helps maintaining blood levels of uric acid (PubMed:12024214, PubMed:22194875). Mediates urate uptake by an exchange with organic anions such as (S)-lactate and nicotinate, and inorganic anion Cl(-) (PubMed:12024214). Other inorganic anions such as Br(-), I(-) and NO3(-) may also act as counteranions that exchange for urate (PubMed:12024214). Also mediates orotate tubular uptake coupled with nicotinate efflux and to a lesser extent with lactate efflux, therefore displaying a potential role in orotate renal reabsorption (PubMed:21350910). Orotate transport is Cl(-)-dependent (PubMed:21350910)

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Hypouricemia, renalMIM #220150

UniProtHypouricemia renal 1

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Hypouricemia, renal; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.30

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

ncbi: 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?

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?

0.37Z-score

OE missense 0.94 (0.86–1.03)

315 obs / 334.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.90 (0.64–1.30)

0≤0.351.4

Missense OE?0.94 (0.86–1.03)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 21 / 23.3Missense obs/exp: 315 / 334.2Syn Z: -0.90

Background carrier burden — how many people carry a rare variant somewhere in SLC22A12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 56

712 rare PASS variants

Rare truncating (LoF)

1 in 660

136 rare PASS variants

Rare synonymous (reference)

1 in 71

360 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC22A12. 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 64	1 in 2,100
South Asian	~43k	1 in 72	1 in 530
Remaining (unassigned)	~30k	1 in 61	1 in 910
European (Finnish)	~27k	1 in 250	1 in 1,700
Admixed American	~22k	1 in 59	1 in 1,200
African / African American	~21k	1 in 57	1 in 1,000
East Asian	~20k	1 in 81	1 in 400
Ashkenazi Jewish	~13k	1 in 420	none seen
Middle Eastern	~2,884	1 in 49	≈ 1 in 1,400

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): 10 of 10 coding exons well covered in gnomAD exomes. Genomes: 9 of 10 (exon 7 below).? see exons ↓

ClinVar

No ClinVar data available.

Protein Context — Lollipop Plot

SLC22A12 · protein map & ClinVar variants

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

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

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

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3

Discovery of Novel Biphenyl Carboxylic Acid Derivatives as Potent URAT1 Inhibitors

Hou X et al.·Molecules

2023

Recent Updates of Natural and Synthetic URAT1 Inhibitors and Novel Screening Methods