TYMP

thymidine phosphorylase, the group of Minor histocompatibility antigens

Basic information

Region (hg38): 22:50525751-50530032

Previous symbols: [ "MNGIE", "ECGF1" ]

Links

ENSG00000025708 ∙ NCBI:1890 ∙ OMIM:131222 ∙ HGNC:3148 ∙ Uniprot:P19971 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial neurogastrointestinal encephalomyopathy (Supportive), mode of inheritance: AR
• mitochondrial DNA depletion syndrome 1 (Strong), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial DNA depletion syndrome 1 (MNGIE type)	AR	Biochemical; Gastrointestinal	Liver transplantation has been described as resulting in short-term survival, stabilization of disease symptoms, decrease in thymidine levels, and clinical improvements	Biochemical; Gastrointestinal; Musculoskeletal; Neurologic	9924029; 10852545; 12177387; 14757860; 16178026; 18787099; 19056268; 19853446; 21412940; 21794876; 32173240
Liver transplantation has been described as resulting in short-term survival, stabilization of disease symptoms, decrease in thymidine levels, and clinical improvements

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TYMP gene.

• not provided (648 variants)
• Mitochondrial DNA depletion syndrome 1 (123 variants)
• Mitochondrial neurogastrointestinal encephalomyopathy (49 variants)
• not specified (41 variants)
• Inborn genetic diseases (19 variants)
• Fatal Infantile Cardioencephalomyopathy (14 variants)
• Cytochrome-c oxidase deficiency disease (13 variants)
• TYMP-related condition (2 variants)
• Spinal muscular atrophy (2 variants)
• Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TYMP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	262	6	269
missense	6	17	146	13	3	185
nonsense	8	7	2			17
start loss						0
frameshift	26	12		1	1	40
inframe indel	1	3	1			5
splice donor/acceptor (+/-2bp)	8	18	1			27
splice region			8	34		42
non coding			6	67	22	95
Total	49	57	157	343	32

Highest pathogenic variant AF is 0.0000920

Variants in TYMP

This is a list of pathogenic ClinVar variants found in the TYMP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
22-50525760-C-T		Mitochondrial DNA depletion syndrome 1 • Mitochondrial complex IV deficiency, nuclear type 1 • Fatal Infantile Cardioencephalomyopathy • not specified	Conflicting classifications of pathogenicity (Jun 14, 2016)
22-50525764-G-A		TYMP-related disorder	Likely benign (Sep 08, 2022)
22-50525767-G-A		Fatal Infantile Cardioencephalomyopathy • Mitochondrial complex IV deficiency, nuclear type 1 • Mitochondrial DNA depletion syndrome 1 • not specified	Conflicting classifications of pathogenicity (Jan 13, 2018)
22-50525773-T-C			Likely benign (Feb 13, 2023)
22-50525775-G-A		Mitochondrial DNA depletion syndrome 1	Uncertain significance (Feb 02, 2022)
22-50525776-C-T		Fatal Infantile Cardioencephalomyopathy • Mitochondrial complex IV deficiency, nuclear type 1 • Mitochondrial DNA depletion syndrome 1 • Mitochondrial neurogastrointestinal encephalomyopathy	Conflicting classifications of pathogenicity (Jan 31, 2024)
22-50525778-G-A		Mitochondrial DNA depletion syndrome 1 • not specified • TYMP-related disorder	Uncertain significance (Dec 12, 2023)
22-50525779-C-T			Likely benign (Nov 14, 2023)
22-50525780-G-C		Mitochondrial neurogastrointestinal encephalomyopathy	Uncertain significance (May 12, 2014)
22-50525781-G-C		Inborn genetic diseases	Uncertain significance (Oct 05, 2023)
22-50525782-C-A			Likely benign (Jan 28, 2023)
22-50525782-C-T			Likely benign (Aug 02, 2022)
22-50525787-G-A			Likely benign (Mar 18, 2023)
22-50525787-G-GA		Mitochondrial DNA depletion syndrome 1	Pathogenic (Jan 14, 2016)
22-50525790-C-T			Uncertain significance (Nov 12, 2021)
22-50525791-G-A			Likely benign (Oct 11, 2023)
22-50525791-G-C			Likely benign (Jan 31, 2024)
22-50525791-G-T			Likely benign (Jul 09, 2023)
22-50525794-C-T			Likely benign (Jan 22, 2024)
22-50525798-G-A			Uncertain significance (Jun 15, 2022)
22-50525800-G-A			Likely benign (Dec 13, 2023)
22-50525802-AG-A			Pathogenic/Likely pathogenic (Mar 18, 2023)
22-50525803-G-A			Likely benign (Dec 20, 2023)
22-50525803-G-T			Likely benign (Sep 20, 2022)
22-50525806-C-T		TYMP-related disorder	Likely benign (Jan 19, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TYMP	protein_coding	protein_coding	ENST00000395681	9	4305

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000117	0.957	125706	0	29	125735	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0969	276	272	1.02	0.0000150	2987
Missense in Polyphen		94	104	0.90381		1171
Synonymous	-0.793	139	128	1.09	0.00000760	1100
Loss of Function	1.82	9	17.1	0.525	8.71e-7	185

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000461	0.000443
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000981	0.0000967
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.000338	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May have a role in maintaining the integrity of the blood vessels. Has growth promoting activity on endothelial cells, angiogenic activity in vivo and chemotactic activity on endothelial cells in vitro. {ECO:0000269|PubMed:1590793}.
• Disease: DISEASE: Mitochondrial DNA depletion syndrome 1, MNGIE type (MTDPS1) [MIM:603041]: A multisystem disease associated with mitochondrial dysfunction. It is clinically characterized by onset between the second and fifth decades of life, ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility (often pseudoobstruction), diffuse leukoencephalopathy, cachexia, peripheral neuropathy, and myopathy. {ECO:0000269|PubMed:12177387, ECO:0000269|PubMed:9924029}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Pyrimidine metabolism - Homo sapiens (human);Bladder cancer - Homo sapiens (human);Drug metabolism - other enzymes - Homo sapiens (human);Fluoropyrimidine Pathway, Pharmacokinetics;Pyrimidine Metabolism;Capecitabine Action Pathway;Capecitabine Metabolism Pathway;UMP Synthase Deiciency (Orotic Aciduria);MNGIE (Mitochondrial Neurogastrointestinal Encephalopathy);Beta Ureidopropionase Deficiency;Dihydropyrimidinase Deficiency;Fluoropyrimidine Activity;Bladder Cancer;Pyrimidine metabolism;pyrimidine deoxyribonucleosides degradation;Pyrimidine catabolism;Nucleobase catabolism;Metabolism of nucleotides;Purine metabolism;Metabolism;Pyrimidine salvage;Nucleotide salvage;Pyrimidine metabolism;Purine nucleotides nucleosides metabolism;Pyrimidine nucleotides nucleosides metabolism (Consensus)

Recessive Scores

• pRec: 0.509

Haploinsufficiency Scores

• pHI: 0.156
• hipred: N
• hipred_score: 0.268
• ghis: 0.534

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.555

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tymp
• Phenotype: immune system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: mitochondrial genome maintenance;angiogenesis;pyrimidine nucleobase metabolic process;pyrimidine nucleoside metabolic process;chemotaxis;regulation of signaling receptor activity;cell differentiation;regulation of myelination;pyrimidine nucleoside salvage;pyrimidine nucleoside catabolic process;regulation of transmission of nerve impulse;regulation of gastric motility
• Cellular component: cytosol
• Molecular function: phosphorylase activity;growth factor activity;thymidine phosphorylase activity;pyrimidine-nucleoside phosphorylase activity;transferase activity, transferring pentosyl groups;protein homodimerization activity