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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
TYMP
thymidine phosphorylase
Chromosome 22 Β· 22q13.33
NCBI Gene: 1890Ensembl: ENSG00000025708.15HGNC: HGNC:3148UniProt: B2RBL3
190PubMed Papers
21Diseases
2Drugs
196Pathogenic Variants
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingprotein homodimerization activitythymidine phosphorylase activitypyrimidine nucleoside metabolic processmitochondrial DNA depletion syndrome 1mitochondrial neurogastrointestinal encephalomyopathycolorectal cancergenetic disorder
✦AI Summary

TYMP (thymidine phosphorylase) is a cytosolic enzyme that catalyzes the reversible phosphorolysis of thymidine, producing molecules utilized for carbon and energy sources or pyrimidine base rescue for nucleotide synthesis 1. The enzyme functions as a homodimer and plays a critical role in maintaining balanced mitochondrial nucleotide pools essential for mtDNA synthesis 1. TYMP deficiency is the primary cause of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a rare autosomal recessive mitochondrial DNA depletion syndrome 23. In MNGIE, TYMP mutations lead to thymidine phosphorylase deficiency, causing accumulation of thymidine and deoxyuridine that impairs mitochondrial DNA maintenance and integrity 2. The disease typically presents in the second decade with severe gastrointestinal dysmotility and peripheral neuropathy, with a mean age at death of 37 years 23. Beyond MNGIE, TYMP has emerged as a potential biomarker in multiple sclerosis, where higher plasma levels show protective effects 4, and in glioma metabolism, where it represents a key metabolic biomarker linked to nucleotide metabolism reprogramming 5. The protein also appears elevated in cerebrospinal fluid of multiple sclerosis patients and correlates with disability outcomes 6.

Sources cited
1
TYMP is involved in mtDNA maintenance and balanced mitochondrial nucleotide pools
PMID: 28215579
2
TYMP mutations cause MNGIE with thymidine phosphorylase deficiency and typical clinical presentation
PMID: 32898308
3
TYMP mutations are associated with mitochondrial neurogastrointestinal encephalopathy presenting before age 20
PMID: 23385875
4
Higher plasma TYMP levels show protective effects against multiple sclerosis risk
PMID: 36864689
5
TYMP emerges as a potential prognostic biomarker linked to nucleotide metabolism in gliomas
PMID: 39562821
6
TYMP is among 11 CSF proteins that predict disability worsening in multiple sclerosis
PMID: 37903821
Disease Associationsβ“˜21
mitochondrial DNA depletion syndrome 1Open Targets
0.81Strong
mitochondrial neurogastrointestinal encephalomyopathyOpen Targets
0.63Moderate
colorectal cancerOpen Targets
0.52Moderate
genetic disorderOpen Targets
0.47Moderate
colorectal neoplasmOpen Targets
0.44Moderate
metastatic colorectal cancerOpen Targets
0.37Weak
LeukoencephalopathyOpen Targets
0.37Weak
mitochondrial diseaseOpen Targets
0.37Weak
colorectal adenocarcinomaOpen Targets
0.37Weak
renal carcinomaOpen Targets
0.36Weak
neoplasmOpen Targets
0.31Weak
gastric cancerOpen Targets
0.27Weak
intestinal pseudo-obstructionOpen Targets
0.27Weak
multiple sclerosisOpen Targets
0.21Weak
fatal infantile encephalocardiomyopathyOpen Targets
0.18Weak
Isolated cytochrome C oxidase deficiencyOpen Targets
0.18Weak
leigh syndrome due to mitochondrial complex iv deficiencyOpen Targets
0.18Weak
chronic lymphocytic leukemiaOpen Targets
0.15Weak
rectum cancerOpen Targets
0.11Weak
breast cancerOpen Targets
0.10Weak
Mitochondrial DNA depletion syndrome 1, MNGIE typeUniProt
Pathogenic Variants196
NM_001953.5(TYMP):c.112G>T (p.Glu38Ter)Pathogenic
Mitochondrial DNA depletion syndrome 1|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 38
NM_001953.5(TYMP):c.866A>C (p.Glu289Ala)Pathogenic
Mitochondrial DNA depletion syndrome 1|not provided|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2026β†’ Residue 289
NM_001953.5(TYMP):c.433G>A (p.Gly145Arg)Pathogenic
Mitochondrial DNA depletion syndrome 1|not provided|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2026β†’ Residue 145
NM_001953.5(TYMP):c.945G>A (p.Trp315Ter)Pathogenic
not provided|Mitochondrial neurogastrointestinal encephalomyopathy|Mitochondrial DNA depletion syndrome 1
β˜…β˜…β˜†β˜†2026β†’ Residue 315
NM_001953.5(TYMP):c.622G>A (p.Val208Met)Pathogenic
Mitochondrial DNA depletion syndrome 1|not provided|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2026β†’ Residue 208
NM_001953.5(TYMP):c.996_1026del (p.Ala333fs)Pathogenic
not provided|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2026β†’ Residue 333
NM_001953.5(TYMP):c.1198_1203del (p.Val400_Leu401del)Pathogenic
Mitochondrial DNA depletion syndrome 1|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2025β†’ Residue 400
NM_001953.5(TYMP):c.865_889dup (p.Ala297fs)Pathogenic
not provided|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2025β†’ Residue 297
NM_001953.5(TYMP):c.11del (p.Ala3_Leu4insTer)Pathogenic
not provided|Mitochondrial DNA depletion syndrome 1|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2025β†’ Residue 3
NM_001953.5(TYMP):c.323G>A (p.Trp108Ter)Pathogenic
Mitochondrial DNA depletion syndrome 1|not provided|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2025β†’ Residue 108
NM_001953.5(TYMP):c.457G>A (p.Gly153Ser)Pathogenic
Mitochondrial DNA depletion syndrome 1|not provided|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2025β†’ Residue 153
NM_001953.5(TYMP):c.403del (p.Ala135fs)Pathogenic
not provided|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2025β†’ Residue 135
NM_001953.5(TYMP):c.1048C>T (p.Gln350Ter)Pathogenic
Mitochondrial DNA depletion syndrome 1
β˜…β˜…β˜†β˜†2025β†’ Residue 350
NM_001953.5(TYMP):c.665A>G (p.Lys222Arg)Likely pathogenic
Mitochondrial DNA depletion syndrome 1|not provided|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2025β†’ Residue 222
NM_001953.5(TYMP):c.929-1G>APathogenic
Mitochondrial DNA depletion syndrome 1|not provided|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2025
NM_001953.5(TYMP):c.418-1G>ALikely pathogenic
Mitochondrial DNA depletion syndrome 1|not provided|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2025
NM_001953.5(TYMP):c.215-1G>CPathogenic
Mitochondrial DNA depletion syndrome 1|not provided|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2025
NM_001953.5(TYMP):c.1159+1G>APathogenic
Inborn genetic diseases|not provided|Mitochondrial DNA depletion syndrome 1
β˜…β˜…β˜†β˜†2025
NM_001953.5(TYMP):c.199C>T (p.Gln67Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 67
NM_001953.5(TYMP):c.340G>A (p.Asp114Asn)Likely pathogenic
Mitochondrial DNA depletion syndrome 1|not provided|Mitochondrial neurogastrointestinal encephalomyopathy
β˜…β˜…β˜†β˜†2025β†’ Residue 114
View on ClinVar β†—
Drug Targets2
TIPIRACILApproved
Thymidine phosphorylase inhibitor
colorectal neoplasm
TIPIRACIL HYDROCHLORIDEApproved
Thymidine phosphorylase inhibitor
colorectal cancer
Related Genes
UMPSProtein interaction100%EIF2B4Protein interaction100%EIF2B1Protein interaction100%DPYDProtein interaction98%UCK1Protein interaction98%UCK2Protein interaction98%
Tissue Expression6 tissues
Lung
100%
Liver
46%
Bone Marrow
13%
Heart
5%
Ovary
3%
Brain
3%
Gene Interaction Network
Click a node to explore
TYMPUMPSEIF2B4EIF2B1DPYDUCK1UCK2
PROTEIN STRUCTURE
Preparing viewer…
PDB1UOU Β· 2.11 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.52LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.20 [0.95–1.52]
RankingsWhere TYMP stands among ~20K protein-coding genes
  • #2,259of 20,598
    Most Researched190 Β· top quartile
  • #561of 1,025
    FDA-Approved Drug Targets2
  • #354of 5,498
    Most Pathogenic Variants196 Β· top 10%
  • #15,260of 17,882
    Most Constrained (LOEUF)1.52
Genes detectedTYMP
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Potential drug targets for multiple sclerosis identified through Mendelian randomization analysis.
PMID: 36864689
Brain Β· 2023
1.00
2
Mitochondrial DNA maintenance defects.
PMID: 28215579
Biochim Biophys Acta Mol Basis Dis Β· 2017
0.90
3
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
0.80
4
Mitochondrial DNA depletion syndromes: review and updates of genetic basis, manifestations, and therapeutic options.
PMID: 23385875
Neurotherapeutics Β· 2013
0.70
5
Distinctive metabolic remodeling in TYMP deficiency beyond mitochondrial dysfunction.
PMID: 37603049
J Mol Med (Berl) Β· 2023
0.68