SLC43A2

Chr 17

solute carrier family 43 member 2

Also known as: LAT4

NCBI Gene: 124935 ENSG00000167703 UniProt: Q8N370 OMIM: 610791

This protein functions as a uniporter that mediates the transport of L-phenylalanine, L-methionine, and branched-chain amino acids across cell membranes through facilitated diffusion, and may control amino acid reabsorption in the kidney and small intestine. Mutations in SLC43A2 cause autosomal recessive nonsyndromic intellectual disability, with patients presenting with developmental delay and intellectual disability. The gene shows tolerance to loss-of-function variants (low pLI of 0.006), suggesting the recessive inheritance pattern observed clinically.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the L-amino acid transporter-3 or SLC43 family of transporters. The encoded protein mediates sodium-, chloride-, and pH-independent transport of L-isomers of neutral amino acids, including leucine, phenylalanine, valine and methionine. This protein may contribute to the transfer of amino acids across the placental membrane to the fetus. [provided by RefSeq, Mar 2016]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.57

Clinical Summary— SLC43A2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 72 VUS of 95 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.006

Z-score 3.25

OE 0.33 (0.20–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.80Z-score

OE missense 0.73 (0.66–0.81)

261 obs / 356.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.33 (0.20–0.57)

0≤0.351.4

Missense OE?0.73 (0.66–0.81)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 9 / 27.4Missense obs/exp: 261 / 356.4Syn Z: 1.17

This gene — mechanism propensity

0.7228th %ile

GOF

0.74top 25%

LOF

0.2776th %ile

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

GOFprediction above median

DNprediction 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

95 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS72

Benign1

Pathogenic

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	1	1
Likely Pathogenic	0	0	0
VUS	71	1	72
Likely Benign	0	0	0
Benign	0	1	1
Total	71	3	74

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

View in ClinVar →

95 pathogenic / likely-pathogenic (of 116) ClinVar copy-number / structural variants overlap SLC43A2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →