SLC1A1

Chr 9AR

solute carrier family 1 member 1

The protein is a high-affinity glutamate transporter that terminates postsynaptic glutamate action and maintains extracellular glutamate concentrations below neurotoxic levels, also transporting aspartate. Autosomal recessive mutations cause dicarboxylic aminoaciduria (glutamate-aspartate transport defect) through a predicted gain-of-function mechanism.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismARLOEUF 0.832 OMIM phenotypes
Clinical SummarySLC1A1
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Gene-Disease Validity (ClinGen)
dicarboxylic aminoaciduria · ARLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.000
Z-score 2.18
OE 0.51 (0.330.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.33Z-score
OE missense 1.22 (1.121.33)
355 obs / 291.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.51 (0.330.83)
00.351.4
Missense OE1.22 (1.121.33)
00.61.4
Synonymous OE1.36
01.21.6
LoF obs/exp: 12 / 23.3Missense obs/exp: 355 / 291.0Syn Z: -2.99
DN
0.82top 10%
GOF
0.84top 5%
LOF
0.1796th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC1A1 · 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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