TYMP

Chr 22AR

thymidine phosphorylase

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

NCBI Gene: 1890ENSG00000025708UniProt: P19971

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]

Primary Disease Associations & Inheritance

Mitochondrial DNA depletion syndrome 1 (MNGIE type)MIM #603041
AR
592
ClinVar variants
176
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TYMP
🧬
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.
📋
ClinVar Variants
176 Pathogenic / Likely Pathogenic· 143 VUS of 592 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.92LOEUF
pLI 0.000
Z-score 1.82
OE 0.52 (0.32–0.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.10Z-score
OE missense 1.02 (0.92–1.12)
276 obs / 271.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.52 (0.32–0.92)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.02 (0.92–1.12)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.09
0≤1.21.6
LoF obs/exp: 9 / 17.1Missense obs/exp: 276 / 271.5Syn Z: -0.79

ClinVar Variant Classifications

592 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic122
Likely Pathogenic54
VUS143
Likely Benign241
Benign9
Conflicting23
122
Pathogenic
54
Likely Pathogenic
143
VUS
241
Likely Benign
9
Benign
23
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
34
17
71
0
122
Likely Pathogenic
28
16
10
0
54
VUS
0
119
14
10
143
Likely Benign
1
5
92
143
241
Benign
1
0
5
3
9
Conflicting
—23
Total64157192156592

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Mitochondrial DNA depletion syndrome 1 (MNGIE type)

MIM #603041

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — TYMP
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Potential drug targets for multiple sclerosis identified through Mendelian randomization analysis.
Lin J et al.·Brain
2023
Mitochondrial DNA maintenance defects.
El-Hattab AW et al.·Biochim Biophys Acta Mol Basis Dis
2017Review
Primary mitochondrial diseases.
Pizzamiglio C et al.·Handb Clin Neurol
2024Review
Proteomic profiling of gliomas unveils immune and metabolism-driven subtypes with implications for anti-nucleotide metabolism therapy.
Zhang J et al.·Nat Commun
2024
Integrated proteomics and scRNA-seq analyses of ovarian cancer reveal molecular subtype-associated cell landscapes and immunotherapy targets.
Tan R et al.·Br J Cancer
2025
Distinctive metabolic remodeling in TYMP deficiency beyond mitochondrial dysfunction.
Du J et al.·J Mol Med (Berl)
2023Functional
Spatial Transcriptomics Reveals Transcriptomic and Immune Microenvironment Reprogramming during Thyroid Carcinoma Dedifferentiation.
Ning K et al.·Adv Sci (Weinh)
2025
Mitochondrial neurogastrointestinal encephalomyopathy in china: a novel TYMP variant and comprehensive clinical-genetic insights.
Xu X et al.·Orphanet J Rare Dis
2025Case report
Novel Mutations of the TYMP Gene in Mitochondrial Neurogastrointestinal Encephalomyopathy: Case Series and Literature Review.
Mojtabavi H et al.·J Mol Neurosci
2021Review
Identifying TYMP as an Immune Prognostic Marker in Clear Cell Renal Cell Carcinoma.
Chen SA et al.·Technol Cancer Res Treat
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools