SLC19A1
Chr 21ARsolute carrier family 19 member 1
Also known as: CHMD, FOLT, IFC-1, IFC1, IMD114, MEGAF, REFC, RFC
The encoded protein is an antiporter that mediates cellular import of reduced folates, particularly N5-methyltetrahydrofolate, and also transports immunoreactive cyclic dinucleotides involved in immune signaling. Autosomal recessive mutations cause folate-responsive megaloblastic anemia and immunodeficiency 114, both responding to folate supplementation. The gene shows tolerance to loss-of-function variants (LOEUF 1.164), suggesting that complete loss of function from both alleles is required for disease manifestation.
Primary Disease Associations & Inheritance
Limited evidence — not for standalone diagnostic reporting
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 (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
SLC19A1 · 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