SLC7A1

Chr 13

solute carrier family 7 member 1

Also known as: ATRC1, CAT-1, ERR, HCAT1, REC1L

The protein functions as a high-affinity transporter for cationic amino acids including arginine, lysine, and ornithine across cell membranes in non-hepatic tissues. Mutations cause lysinuric protein intolerance, an autosomal recessive disorder affecting amino acid transport that typically presents in infancy with failure to thrive, protein aversion, and can involve multiple organ systems including lungs, kidneys, and immune system. The gene is highly constrained against loss-of-function mutations, indicating that such variants are likely to be pathogenic.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.27
Clinical SummarySLC7A1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 57 VUS of 112 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.27LOEUF
pLI 0.993
Z-score 4.12
OE 0.08 (0.030.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
3.30Z-score
OE missense 0.53 (0.470.59)
206 obs / 388.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.08 (0.030.27)
00.351.4
Missense OE0.53 (0.470.59)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 2 / 23.6Missense obs/exp: 206 / 388.9Syn Z: 0.19
DN
0.5378th %ile
GOF
0.6930th %ile
LOF
0.4430th %ile

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.27
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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

112 submitted variants in ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic3
VUS57
Likely Benign5
Benign6
32
Pathogenic
3
Likely Pathogenic
57
VUS
5
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
32
0
32
Likely Pathogenic
0
0
3
0
3
VUS
0
53
4
0
57
Likely Benign
0
3
0
2
5
Benign
0
1
0
5
6
Total057397103

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC7A1 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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