SLC32A1

Chr 20AD

solute carrier family 32 member 1

Also known as: DEE114, GEFSP12, VGAT, VIAAT, VIAAT GEFSP12

The encoded protein transports GABA and glycine into synaptic vesicles as an integral membrane protein. Mutations cause developmental and epileptic encephalopathy 114 and generalized epilepsy with febrile seizures plus type 12 through an autosomal dominant inheritance pattern. The pathogenic mechanism involves gain-of-function mutations that disrupt normal inhibitory neurotransmitter packaging.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
MultiplemechanismADLOEUF 0.322 OMIM phenotypes
Clinical SummarySLC32A1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.32LOEUF
pLI 0.967
Z-score 3.35
OE 0.07 (0.020.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.30Z-score
OE missense 0.63 (0.560.71)
188 obs / 300.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.07 (0.020.32)
00.351.4
Missense OE0.63 (0.560.71)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 1 / 15.0Missense obs/exp: 188 / 300.3Syn Z: -0.43
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateSLC32A1-related developmental and epileptic encephalopathyOTHERAD
DN
0.5576th %ile
GOF
0.75top 25%
LOF
0.4726th %ile

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports loss-of-function (haploinsufficiency). Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFLOEUF 0.32
GOFprediction 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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SLC32A1 · 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

No active trials found for this gene.

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