SLC47A2

Chr 17

solute carrier family 47 member 2

Also known as: MATE2, MATE2-B, MATE2-K, MATE2K

This protein functions as a multidrug efflux pump that mediates the excretion of cationic compounds, drugs, toxins and endogenous metabolites including creatinine and thiamine through the kidney via H+/organic cation antiport activity. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by severe intellectual disability, epilepsy, and progressive brain atrophy. The gene shows extremely low constraint against loss-of-function variants, consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.13
Clinical SummarySLC47A2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.13LOEUF
pLI 0.000
Z-score 0.97
OE 0.81 (0.591.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.35Z-score
OE missense 0.95 (0.861.04)
326 obs / 344.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.81 (0.591.13)
00.351.4
Missense OE0.95 (0.861.04)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 25 / 30.8Missense obs/exp: 326 / 344.0Syn Z: 0.19
DN
0.74top 25%
GOF
0.6832th %ile
LOF
0.2776th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC47A2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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