SLC29A4
Chr 7solute carrier family 29 member 4
Also known as: ENT4, PMAT
The protein functions as an electrogenic voltage-dependent transporter that mediates uptake of monoamine neurotransmitters (serotonin, dopamine, norepinephrine) and clearance of cationic compounds from cerebrospinal fluid through the blood-brain barrier. Mutations cause autosomal recessive developmental and epileptic encephalopathy, characterized by early-onset seizures, severe developmental delay, and progressive neurodegeneration. The gene shows low constraint against loss-of-function variants (pLI near 0), consistent with the recessive inheritance pattern observed clinically.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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
SLC29A4 · 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