SLC47A2

Chr 17

solute carrier family 47 member 2

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

NCBI Gene: 146802 ENSG00000180638 UniProt: Q86VL8

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.

ResearchSummary from RefSeq, UniProt

This gene encodes a protein belonging to a family of transporters involved in excretion of toxic electrolytes, both endogenous and exogenous, through urine and bile. This transporter family shares homology with the bacterial MATE (multidrug and toxin extrusion) protein family responsible for drug resistance. This gene is one of two members of the MATE transporter family located near each other on chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.13

Clinical Summary— SLC47A2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

83 VUS of 108 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.13LOEUF

pLI 0.000

Z-score 0.97

OE 0.81 (0.59–1.13)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.35Z-score

OE missense 0.95 (0.86–1.04)

326 obs / 344.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.81 (0.59–1.13)

0≤0.351.4

Missense OE?0.95 (0.86–1.04)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 25 / 30.8Missense obs/exp: 326 / 344.0Syn Z: 0.19

This gene — mechanism propensity

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

108 submitted variants in ClinVar

ClinVar

Classification Summary

VUS83

Likely Benign8

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	83	0	83
Likely Benign	6	2	8
Benign	1	2	3
Total	90	4	94

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

View in ClinVar →

98 pathogenic / likely-pathogenic (of 116) ClinVar copy-number / structural variants overlap SLC47A2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →