SLC7A4

Chr 22

solute carrier family 7 member 4

Also known as: CAT-4, CAT4, HCAT3, VH

The SLC7A4 protein transports cationic amino acids including arginine, lysine, and ornithine across cell membranes. Mutations cause autosomal recessive lysinuric protein intolerance, characterized by defective amino acid transport leading to hyperammonemia, failure to thrive, hepatosplenomegaly, and osteoporosis typically presenting in infancy or early childhood. The gene shows tolerance to loss-of-function variants (low constraint), consistent with the recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.23
Clinical SummarySLC7A4
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
1.23LOEUF
pLI 0.000
Z-score 0.90
OE 0.76 (0.481.23)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.07Z-score
OE missense 0.99 (0.911.08)
393 obs / 397.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.76 (0.481.23)
00.351.4
Missense OE0.99 (0.911.08)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 12 / 15.9Missense obs/exp: 393 / 397.1Syn Z: 0.05
DN
0.80top 25%
GOF
0.78top 25%
LOF
0.2091th %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

SLC7A4 · 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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