SLC1A2

Chr 11AD

solute carrier family 1 member 2

Also known as: DEE41, EAAT2, EIEE41, GLT-1, GLT1, HBGT

NCBI Gene: 6506ENSG00000110436UniProt: P43004

This gene encodes a member of a family of solute transporter proteins. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system. Glutamate clearance is necessary for proper synaptic activation and to prevent neuronal damage from excessive activation of glutamate receptors. Improper regulation of this gene is thought to be associated with several neurological disorders. Alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2017]

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 41MIM #617105
AD
556
ClinVar variants
27
Pathogenic / LP
0.71
pLI score
0
Active trials
Clinical Summary— SLC1A2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.71) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 222 VUS of 556 total submissions
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.42LOEUF
pLI 0.710
Z-score 3.51
OE 0.19 (0.09–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
2.28Z-score
OE missense 0.65 (0.58–0.73)
217 obs / 334.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.19 (0.09–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.58–0.73)
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.1.03
0≤1.21.6
LoF obs/exp: 4 / 21.6Missense obs/exp: 217 / 334.6Syn Z: -0.29

ClinVar Variant Classifications

556 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic8
VUS222
Likely Benign229
Benign61
Conflicting17
19
Pathogenic
8
Likely Pathogenic
222
VUS
229
Likely Benign
61
Benign
17
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
17
0
19
Likely Pathogenic
1
7
0
0
8
VUS
10
191
20
1
222
Likely Benign
1
42
73
113
229
Benign
0
28
14
19
61
Conflicting
—17
Total12270124133556

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC1A2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SLC1A2-related epileptic encephalopathy

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Developmental and epileptic encephalopathy 41

MIM #617105

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Breast cancer cell-secreted miR-199b-5p hijacks neurometabolic coupling to promote brain metastasis.
Ruan X et al.·Nat Commun
2024
SLC1A2 rs3794087 variant and risk for essential tremor: a systematic review and meta-analysis.
Jiménez-Jiménez FJ et al.·Pharmacogenet Genomics
2015Meta-analysis
Analysis of variant rs3794087 in SLC1A2 and Parkinson's disease in a Chinese Han population: A case-control study and meta-analysis.
Cheng Y et al.·Neurosci Lett
2018Meta-analysis
SLC gene mutations and pediatric neurological disorders: diverse clinical phenotypes in a Saudi Arabian population.
Mir A et al.·Hum Genet
2022
The severity of SLC1A2-associated neurodevelopmental disorders correlates with transporter dysfunction.
Kovermann P et al.·EBioMedicine
2025
SLC1A2 rs3794087 variant and risk for migraine.
García-Martín E et al.·J Neurol Sci
2014
CD44 and SLC1A2 are commonly regulated but do not form a fusion transcript in ER+ breast cancer.
Bonechi F et al.·Mol Cell Biochem
2025
Recurrent SLC1A2 variants cause epilepsy via a dominant negative mechanism.
Stergachis AB et al.·Ann Neurol
2019Functional
Genetics of essential tremor: meta-analysis and review.
Kuhlenbäumer G et al.·Neurology
2014Review
Genetic Risk Factors for Essential Tremor: A Review.
Siokas V et al.·Tremor Other Hyperkinet Mov (N Y)
2020Review
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