SLC25A12
Chr 2ARsolute carrier family 25 member 12
Also known as: AGC1, ARALAR, DEE39, EIEE39
This gene encodes a calcium-binding mitochondrial carrier protein that exchanges aspartate for glutamate across the inner mitochondrial membrane. Mutations cause developmental and epileptic encephalopathy 39 through an autosomal recessive inheritance pattern, with a predicted gain-of-function mechanism. The protein dysfunction may also result in global cerebral hypomyelination.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SLC25A12 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools