SLC22A6

Chr 11

solute carrier family 22 member 6

Also known as: HOAT1, OAT1, PAHT, ROAT1

NCBI Gene: 9356 ENSG00000197901 UniProt: Q4U2R8 OMIM: 607582

The encoded protein is an organic anion transporter that mediates sodium-independent uptake of organic anions including biopterins, prostaglandins, and uremic toxins across the basolateral membrane of proximal tubule cells, contributing to renal elimination of potentially toxic compounds. Mutations cause autosomal recessive renal hypouricemia with risk of exercise-induced acute kidney injury and nephrolithiasis. The gene shows very low constraint against loss-of-function variants (pLI near zero, LOEUF 0.99), consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is involved in the sodium-dependent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and may be localized to the basolateral membrane. Four transcript variants encoding four different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.99

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.99LOEUF

pLI 0.000

Z-score 1.60

OE 0.64 (0.43–0.99)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.58Z-score

OE missense 0.91 (0.83–1.00)

305 obs / 335.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.64 (0.43–0.99)

0≤0.351.4

Missense OE?0.91 (0.83–1.00)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 15 / 23.3Missense obs/exp: 305 / 335.0Syn Z: 0.24

Background carrier burden — how many people carry a rare variant somewhere in SLC22A6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

673 rare PASS variants

Rare truncating (LoF)

1 in 1,400

114 rare PASS variants

Rare synonymous (reference)

1 in 120

314 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC22A6. 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 150	1 in 1,500
South Asian	~43k	1 in 75	1 in 600
Remaining (unassigned)	~30k	1 in 120	1 in 1,200
European (Finnish)	~27k	1 in 410	≈ 1 in 13,000
Admixed American	~22k	1 in 69	1 in 520
African / African American	~21k	1 in 75	1 in 1,100
East Asian	~20k	1 in 85	1 in 820
Ashkenazi Jewish	~13k	1 in 590	1 in 1,900
Middle Eastern	~2,884	1 in 120	≈ 1 in 720

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): All 10 coding exons well covered in gnomAD exomes and genomes.? see exons ↓