TYMP
Chr 22ARthymidine phosphorylase
Also known as: ECGF, ECGF1, MEDPS1, MNGIE, MTDPS1, PDECGF, TP, hPD-ECGF
The protein encoded by this gene functions as an angiogenic factor that specifically promotes blood vessel formation by stimulating endothelial cell growth. Mutations cause mitochondrial DNA depletion syndrome 1 (MNGIE type), also known as mitochondrial neurogastrointestinal encephalomyopathy, which is inherited in an autosomal recessive pattern. The pathogenic mechanism involves dominant negative effects that disrupt normal mitochondrial DNA maintenance.
Definitive — sufficient evidence for diagnostic panels
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
100 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 | 3 | 0 | 0 | 0 | 3 |
Likely Pathogenic | 13 | 3 | 0 | 0 | 16 |
VUS | 0 | 41 | 3 | 4 | 48 |
Likely Benign | 0 | 1 | 15 | 15 | 31 |
Benign | 1 | 0 | 0 | 0 | 1 |
Conflicting | — | 1 | |||
| Total | 17 | 45 | 18 | 19 | 100 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TYMP · 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