SLC7A2

Chr 8

solute carrier family 7 member 2

Also known as: ATRC2, CAT-2A, CAT-2B, CAT2, HCAT2, SLC7A2A, SLC7A2B

The protein functions as a cationic amino acid transporter responsible for cellular uptake of arginine, lysine, ornithine, and homoarginine across cell membranes. Mutations cause lysinuric protein intolerance, an autosomal recessive disorder characterized by defective transport of these amino acids leading to failure to thrive, hepatosplenomegaly, osteoporosis, and potential pulmonary complications. The gene is extremely intolerant to loss-of-function variants and has a GeneReviews entry reflecting its established clinical significance.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
13
Pubs (1 yr)
80
P/LP submissions
0%
P/LP missense
1.01
LOEUF
Multiple*
Mechanism· predicted
Clinical SummarySLC7A2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
80 unique Pathogenic / Likely Pathogenic· 115 VUS of 236 total submissions
📖
GeneReview available — SLC7A2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.000
Z-score 1.50
OE 0.70 (0.501.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.41Z-score
OE missense 1.20 (1.111.29)
477 obs / 398.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.70 (0.501.01)
00.351.4
Missense OE1.20 (1.111.29)
00.61.4
Synonymous OE1.20
01.21.6
LoF obs/exp: 21 / 29.8Missense obs/exp: 477 / 398.0Syn Z: -1.96
DN
0.75top 25%
GOF
0.79top 25%
LOF
0.2189th %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

236 submitted variants in ClinVar

Classification Summary

Pathogenic76
Likely Pathogenic4
VUS115
Likely Benign7
Benign13
76
Pathogenic
4
Likely Pathogenic
115
VUS
7
Likely Benign
13
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
76
0
76
Likely Pathogenic
0
0
4
0
4
VUS
0
109
6
0
115
Likely Benign
0
6
1
0
7
Benign
0
5
3
5
13
Total0120905215

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC7A2 · protein map & ClinVar variants

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

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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