SLC25A39
Chr 17solute carrier family 25 member 39
Also known as: CGI-69, CGI69
The protein functions as a mitochondrial transporter that imports glutathione from the cytosol into mitochondria, where it is essential for iron-sulfur cluster protein stability and erythropoiesis. Biallelic mutations cause a severe mitochondrial disorder characterized by early-onset developmental delay, hypotonia, seizures, and often early lethality, following an autosomal recessive inheritance pattern. The pathogenic mechanism involves loss of mitochondrial glutathione import, leading to oxidative stress and impaired iron-sulfur cluster metabolism.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
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
115 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 10 | 0 | 10 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 0 | 81 | 1 | 0 | 82 |
Likely Benign | 0 | 4 | 0 | 1 | 5 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 85 | 11 | 1 | 97 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SLC25A39 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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