TYMP

Chr 22AR

thymidine phosphorylase

Also known as: ECGF, ECGF1, MEDPS1, MNGIE, MTDPS1, PDECGF, TP, hPD-ECGF

This gene encodes an angiogenic factor which promotes angiogenesis in vivo and stimulates the in vitro growth of a variety of endothelial cells. It has a highly restricted target cell specificity acting only on endothelial cells. Mutations in this gene have been associated with mitochondrial neurogastrointestinal encephalomyopathy. Multiple alternatively spliced transcript variants have been identified. [provided by RefSeq, Apr 2012]

OMIMResearchGenerating clinical summary…
MultiplemechanismARLOEUF 0.921 OMIM phenotype
Clinical SummaryTYMP
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.92LOEUF
pLI 0.000
Z-score 1.82
OE 0.52 (0.320.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.10Z-score
OE missense 1.02 (0.921.12)
276 obs / 271.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.52 (0.320.92)
00.351.4
Missense OE?1.02 (0.921.12)
00.61.4
Synonymous OE?1.09
01.21.6
LoF obs/exp: 9 / 17.1Missense obs/exp: 276 / 271.5Syn Z: -0.79

This gene — mechanism propensity

DN
0.73top 25%
GOF
0.6541th %ile
LOF
0.2583th %ile

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.

DNprediction above median
GOFprediction above median

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

TYMP · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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