SLC15A2

Chr 3

solute carrier family 15 member 2

Also known as: PEPT2

NCBI Gene: 6565 ENSG00000163406 UniProt: Q16348 OMIM: 602339

The SLC15A2 protein is a proton-coupled transporter that absorbs dipeptides and tripeptides from kidney filtrate and transports bacterial peptidoglycans for innate immune recognition. Mutations cause autosomal recessive familial hypercalciuric nephrolithiasis, presenting with kidney stones and hypercalciuria. The gene shows low constraint against loss-of-function variants (pLI near zero), consistent with recessive inheritance requiring biallelic mutations for disease manifestation.

OMIM ResearchSummary from RefSeq, UniProt

The mammalian kidney expresses a proton-coupled peptide transporter that is responsible for the absorption of small peptides, as well as beta-lactam antibiotics and other peptide-like drugs, from the tubular filtrate. This transporter, SLC15A2, belongs to the same gene family as SLC15A1 (MIM 600544), the proton-coupled peptide transporter found in the small intestine (Liu et al, 1995 [PubMed 7756356]).[supplied by OMIM, Feb 2011]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.05

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.000

Z-score 1.27

OE 0.79 (0.60–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.20Z-score

OE missense 0.97 (0.89–1.06)

376 obs / 387.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.60–1.05)

0≤0.351.4

Missense OE?0.97 (0.89–1.06)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 35 / 44.1Missense obs/exp: 376 / 387.1Syn Z: 0.00

Background carrier burden — how many people carry a rare variant somewhere in SLC15A2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 86

962 rare PASS variants

Rare truncating (LoF)

1 in 640

154 rare PASS variants

Rare synonymous (reference)

1 in 160

321 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLC15A2. 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 110	1 in 890
South Asian	~43k	1 in 65	1 in 630
Remaining (unassigned)	~30k	1 in 87	1 in 620
European (Finnish)	~27k	1 in 470	1 in 3,300
Admixed American	~22k	1 in 88	1 in 550
African / African American	~21k	1 in 63	1 in 1,100
East Asian	~20k	1 in 54	1 in 1,100
Ashkenazi Jewish	~13k	1 in 1,200	none seen
Middle Eastern	~2,884	1 in 78	1 in 240

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): 21 of 22 coding exons well covered in gnomAD exomes; exon 20 marginal. Genomes: all 22.? see exons ↓