SLC5A12

Chr 11

solute carrier family 5 member 12

Also known as: SMCT2

NCBI Gene: 159963 ENSG00000148942 UniProt: Q1EHB4 OMIM: 612455

The SLC5A12 protein functions as a low-affinity sodium-coupled transporter that mediates reabsorption of monocarboxylates including lactate, pyruvate, and other organic acids in the proximal tubule of the kidney and small intestine. Mutations in SLC5A12 cause autosomal recessive renal lactate wasting, which can lead to metabolic complications due to impaired lactate reabsorption. This gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Normal blood lactate is maintained at about 1.5 mM, and little filtered lactate is excreted in urine. Reabsorption of lactate is mediated by the low-affinity Na(+)-coupled lactate transporter SLC5A12 in the initial part of the proximal tubule and by the high-affinity Na(+)-coupled lactate transporter SLC5A8 (MIM 608044) in the distal proximal tubule (Gopal et al., 2007 [PubMed 17692818]).[supplied by OMIM, Dec 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.70

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.70LOEUF

pLI 0.000

Z-score 2.95

OE 0.46 (0.31–0.70)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.15Z-score

OE missense 0.82 (0.74–0.91)

267 obs / 325.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.31–0.70)

0≤0.351.4

Missense OE?0.82 (0.74–0.91)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 16 / 34.7Missense obs/exp: 267 / 325.5Syn Z: -0.09

Background carrier burden — how many people carry a rare variant somewhere in SLC5A12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

754 rare PASS variants

Rare truncating (LoF)

1 in 1,600

101 rare PASS variants

Rare synonymous (reference)

1 in 170

294 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC5A12. 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 120	1 in 1,800
South Asian	~43k	1 in 120	1 in 1,100
Remaining (unassigned)	~30k	1 in 75	1 in 2,100
European (Finnish)	~27k	1 in 220	1 in 1,900
Admixed American	~22k	1 in 99	1 in 1,000
African / African American	~21k	1 in 95	1 in 1,000
East Asian	~20k	1 in 73	1 in 1,200
Ashkenazi Jewish	~13k	1 in 1,200	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 110	≈ 1 in 2,900

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): 14 of 15 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 15.? see exons ↓