SLC6A11

Chr 3

solute carrier family 6 member 11

Also known as: GAT-3, GAT3, GAT4

NCBI Gene: 6538ENSG00000132164UniProt: P48066

The protein encoded by this gene is a sodium-dependent transporter that uptakes gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, which ends the GABA neurotransmission. Defects in this gene may result in epilepsy, behavioral problems, or intellectual problems. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

122
ClinVar variants
39
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC6A11
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 75 VUS of 122 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.
0.64LOEUF
pLI 0.000
Z-score 3.15
OE 0.40 (0.26–0.64)
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.
2.56Z-score
OE missense 0.62 (0.56–0.69)
227 obs / 364.6 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.0.40 (0.26–0.64)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.62 (0.56–0.69)
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.1.06
0≤1.21.6
LoF obs/exp: 13 / 32.3Missense obs/exp: 227 / 364.6Syn Z: -0.54

ClinVar Variant Classifications

122 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic3
VUS75
Likely Benign2
Benign4
Conflicting2
36
Pathogenic
3
Likely Pathogenic
75
VUS
2
Likely Benign
4
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
36
0
36
Likely Pathogenic
0
0
3
0
3
VUS
0
70
5
0
75
Likely Benign
0
1
0
1
2
Benign
0
1
0
3
4
Conflicting
—2
Total072444122

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC6A11 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
4-Phenylbutyrate restored GABA uptake, mitigated seizures in SLC6A1 and SLC6A11 microdeletions/3p- syndrome: From cellular models to human patients.
DeLeeuw MB et al.·Epilepsy Res
2025Cohort
Whole-genome sequencing analysis of clozapine-induced myocarditis.
Narang A et al.·Pharmacogenomics J
2022
Association of CYP3A4*1B and SLC6A11 Genetic Variants with Epilepsy Risk And Antiepileptic Drug Response in an Iraqi Population.
Hoidy WH et al.·Mol Neurobiol
2025
3p25.3 microdeletion of GABA transporters SLC6A1 and SLC6A11 results in intellectual disability, epilepsy and stereotypic behavior.
Dikow N et al.·Am J Med Genet A
2014Case report
A New Genomewide Association Meta-Analysis of Alcohol Dependence.
Zuo L et al.·Alcohol Clin Exp Res
2015Meta-analysis
DNA methylation associations with cognitive function in early-stage hormone receptor-positive breast cancer patients.
Liu S et al.·Epigenomics
2025Cohort
Association between the SLC6A12 gene and negative symptoms of schizophrenia in a Korean population.
Park HJ et al.·Psychiatry Res
2011
EEF1A2 and ERN2 could potentially discriminate metastatic status of mediastinal lymph node in lung adenocarcinomas harboring EGFR 19Del/L858R mutations.
Xia L et al.·Thorac Cancer
2020
A 9-year-old male with a duplication of chromosome 3p25.3p26.2: clinical report and gene expression analysis.
Bittel DC et al.·Am J Med Genet A
2006Case report
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