SLC6A1

Chr 3AD

solute carrier family 6 member 1

Also known as: GABATHG, GABATR, GAT1, MAE, hGAT-1

NCBI Gene: 6529ENSG00000157103UniProt: P30531

The protein encoded by this gene is a gamma-aminobutyric acid (GABA) transporter that localizes to the plasma membrane. The encoded protein removes GABA from the synaptic cleft, restoring it to presynaptic terminals. [provided by RefSeq, Jan 2017]

Primary Disease Associations & Inheritance

Myoclonic-atonic epilepsyMIM #616421
AD
795
ClinVar variants
153
Pathogenic / LP
1.00
pLI score· haploinsufficient
3
Active trials
Clinical Summary— SLC6A1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
153 Pathogenic / Likely Pathogenic· 274 VUS of 795 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.15LOEUF
pLI 1.000
Z-score 5.05
OE 0.03 (0.01–0.15)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
4.18Z-score
OE missense 0.39 (0.34–0.45)
144 obs / 370.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.03 (0.01–0.15)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.39 (0.34–0.45)
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.1.10
0≤1.21.6
LoF obs/exp: 1 / 31.7Missense obs/exp: 144 / 370.1Syn Z: -0.96

ClinVar Variant Classifications

795 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic87
Likely Pathogenic66
VUS274
Likely Benign308
Benign27
Conflicting33
87
Pathogenic
66
Likely Pathogenic
274
VUS
308
Likely Benign
27
Benign
33
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
23
20
44
0
87
Likely Pathogenic
16
39
11
0
66
VUS
2
239
27
6
274
Likely Benign
0
32
118
158
308
Benign
0
13
11
3
27
Conflicting
—33
Total41343211167795

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC6A1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SLC6A1-related epilepsy with myoclonic-atonic seizures

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Myoclonic-atonic epilepsy

MIM #616421

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — SLC6A1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
SLC6A1 variant pathogenicity, molecular function and phenotype: a genetic and clinical analysis.
Stefanski A et al.·Brain
2023
Whole-exome sequencing analysis identifies risk genes for schizophrenia.
Chick SL et al.·Nat Commun
2025
The Brain Gene Registry: a data snapshot.
Baldridge D et al.·J Neurodev Disord
2024
Phenylbutyrate for monogenetic epilepsy: Literature review.
Stone A et al.·Epilepsy Res
2025Review
Clinical and genetic landscape of epilepsies with absence seizures and single-gene etiology.
Balestrini S et al.·Epilepsia
2026
Neurodevelopmental phenotypes associated with pathogenic variants in SLC6A1.
Kahen A et al.·J Med Genet
2022
Patient-derived SLC6A1 variant S295L results in an epileptic phenotype similar to haploinsufficient mice.
Lindquist BE et al.·Epilepsia
2023
Common molecular mechanisms of SLC6A1 variant-mediated neurodevelopmental disorders in astrocytes and neurons.
Mermer F et al.·Brain
2021Functional
Construction of a prognostic model based on disulfidptosis-related genes and identification of CCNA2 as a novel biomarker for hepatocellular carcinoma.
Wang T et al.·Biol Direct
2024Functional
Consistency of parent-report SLC6A1 data in Simons Searchlight with Provider-Based Publications.
Bain JM et al.·J Neurodev Disord
2022
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
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10
STXBP1 Encephalopathy With Epilepsy, SLC6A1 Neurodevelopmental DisorderDevelopmental and Epileptic Encephalopathy

Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy

ACTIVE NOT RECRUITING
NCT04937062Phase EARLY_PHASE1Weill Medical College of Cornell UniversityStarted 2021-03-01
Glycerol Phenylbutyrate 1100 MG/ML [Ravicti]
SLC6A1

Gene Therapy for SLC6A1 Neurodevelopmental Disorder

ENROLLING BY INVITATION
NCT07173153Phase PHASE1, PHASE2Emily de los ReyesStarted 2025-08-25
AAV9.SLC6A1 Gene Therapy

External Resources

Links to major genomics databases and tools