SLC1A1

Chr 9AR

solute carrier family 1 member 1

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

NCBI Gene: 6505ENSG00000106688UniProt: P43005

This gene encodes a member of the high-affinity glutamate transporters that play an essential role in transporting glutamate across plasma membranes. In brain, these transporters are crucial in terminating the postsynaptic action of the neurotransmitter glutamate, and in maintaining extracellular glutamate concentrations below neurotoxic levels. This transporter also transports aspartate, and mutations in this gene are thought to cause dicarboxylicamino aciduria, also known as glutamate-aspartate transport defect. [provided by RefSeq, Mar 2010]

Primary Disease Associations & Inheritance

{?Schizophrenia susceptibility 18}MIM #615232
Dicarboxylic aminoaciduriaMIM #222730
AR
UniProtSchizophrenia 18
443
ClinVar variants
130
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC1A1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
130 Pathogenic / Likely Pathogenic· 144 VUS of 443 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.83LOEUF
pLI 0.000
Z-score 2.18
OE 0.51 (0.33–0.83)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.33Z-score
OE missense 1.22 (1.12–1.33)
355 obs / 291.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.51 (0.33–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.22 (1.12–1.33)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.36
0≤1.21.6
LoF obs/exp: 12 / 23.3Missense obs/exp: 355 / 291.0Syn Z: -2.99

ClinVar Variant Classifications

443 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic123
Likely Pathogenic7
VUS144
Likely Benign19
Benign32
Conflicting1
123
Pathogenic
7
Likely Pathogenic
144
VUS
19
Likely Benign
32
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
123
0
123
Likely Pathogenic
0
0
7
0
7
VUS
1
85
54
4
144
Likely Benign
0
4
9
6
19
Benign
0
1
27
4
32
Conflicting
—1
Total19022014326

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{?Schizophrenia susceptibility 18}

MIM #615232

Molecular basis of disorder known

Dicarboxylic aminoaciduria

MIM #222730

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SLC1A1 mediated glutamine addiction and contributed to natural killer T-cell lymphoma progression with immunotherapeutic potential.
Xiong J et al.·EBioMedicine
2021
Myeloid cell genome-wide screen identifies variants associated with Mycobacterium tuberculosis-induced cytokine transcriptional responses.
Ivie JJ et al.·J Clin Invest
2025
CircRNA ZFR promotes cell progression by regulating miR-96a-5p/SLC1A1 axis in hepatocellular carcinoma.
Bongolo CC et al.·Sci Rep
2025
Rare SLC1A1 variants in hot water epilepsy.
Karan KR et al.·Hum Genet
2017
Relationship between gene-environment interaction and obsessive-compulsive disorder: A systematic review.
Wang L et al.·J Psychiatr Res
2023Review
Functional studies and rare variant screening of SLC1A1/EAAC1 in males with obsessive-compulsive disorder.
Veenstra-VanderWeele J et al.·Psychiatr Genet
2012Functional
Glutamate transporter SLC1A1 is associated with clear cell renal cell carcinoma.
Ergün S et al.·Turk J Med Sci
2019
Whole-genome sequencing reveals individual and cohort level insights into chromosome 9p syndromes.
Wang Y et al.·Genome Med
2025Cohort
Influence of polymorphisms in genes SLC1A1, GRIN2B, and GRIK2 on clozapine-induced obsessive-compulsive symptoms.
Cai J et al.·Psychopharmacology (Berl)
2013
Genetic and pharmacogenetic study of glutamate transporter (SLC1A1) in Iranian patients with obsessive-compulsive disorder.
Abdolhosseinzadeh S et al.·J Clin Pharm Ther
2019Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools