SLC1A1

Chr 9AR

solute carrier family 1 member 1

Also known as: DCBXA, EAAC1, EAAT3, SCZD18, hEAAC1

NCBI Gene: 6505ENSG00000106688UniProt: P43005OMIM: 133550

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 Summary— SLC1A1
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Gene-Disease Validity (ClinGen)
dicarboxylic aminoaciduria · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
173 unique Pathogenic / Likely Pathogenic· 179 VUS of 441 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.83LOEUF
pLI 0.000
Z-score 2.18
OE 0.51 (0.33–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-1.33Z-score
OE missense 1.22 (1.12–1.33)
355 obs / 291.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.51 (0.33–0.83)
0≤0.351.4
Missense OE1.22 (1.12–1.33)
0≤0.61.4
Synonymous OE1.36
0≤1.21.6
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

441 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic165
Likely Pathogenic8
VUS179
Likely Benign22
Benign46
Conflicting5
165
Pathogenic
8
Likely Pathogenic
179
VUS
22
Likely Benign
46
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
165
0
165
Likely Pathogenic
0
1
7
0
8
VUS
3
93
74
9
179
Likely Benign
0
4
12
6
22
Benign
0
2
36
8
46
Conflicting
—5
Total310029423425

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

View 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Structure-guided optimization of SLC1A1/EAAT3-selective inhibitors targeting renal cancer metabolism.
Koochaki P et al.·EMBO J
2026
The SLC1A1/EAAT3 dicarboxylic amino acid transporter is an epigenetically dysregulated nutrient carrier that sustains oncogenic metabolic programs.
Grubb T et al.·Nat Commun
2025Open Access
CircRNA ZFR promotes cell progression by regulating miR-96a-5p/SLC1A1 axis in hepatocellular carcinoma.
Bongolo CC et al.·Sci Rep
2025Open Access
Early Enhancement in Contrast-Enhanced Computed Tomography Is an Index of DUSP9, SLPI, ALDH1L2, and SLC1A1 Expression in Canine Hepatocellular Carcinoma: A Preliminary Study.
Tanaka T et al.·Vet Sci
2025Open Access
Association of rs11081062 polymorphism of DLGAP1 gene and levels of SLC1A1 protein with obsessive-compulsive disorder.
Akkuş Eİ et al.·Nucleosides Nucleotides Nucleic Acids
2024
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients