SLC15A5

Chr 12

solute carrier family 15 member 5

The protein functions as a proton oligopeptide cotransporter that transports small peptides across cellular membranes. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly, which typically presents in early infancy with seizures, developmental delay, and reduced head circumference. This gene shows minimal constraint against loss-of-function variants in population databases.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
38
P/LP submissions
0%
P/LP missense
1.18
LOEUF
Multiple*
Mechanism· predicted
Clinical SummarySLC15A5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
38 unique Pathogenic / Likely Pathogenic· 93 VUS of 145 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.18LOEUF
pLI 0.000
Z-score 0.94
OE 0.78 (0.531.18)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.91Z-score
OE missense 0.84 (0.760.94)
226 obs / 267.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.78 (0.531.18)
00.351.4
Missense OE0.84 (0.760.94)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 16 / 20.6Missense obs/exp: 226 / 267.8Syn Z: 0.87
DN
0.74top 25%
GOF
0.7126th %ile
LOF
0.2288th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

145 submitted variants in ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic1
VUS93
Likely Benign7
37
Pathogenic
1
Likely Pathogenic
93
VUS
7
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
0
0
1
0
1
VUS
0
88
5
0
93
Likely Benign
0
4
3
0
7
Benign
0
0
0
0
0
Total092460138

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC15A5 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found