TYMP (thymidine phosphorylase)

Gene

• Entrez ID: 1890
• Gene name: Thymidine phosphorylase
• Gene symbol: TYMP
• Synonyms (NCBI Gene): ECGF, ECGF1, MEDPS1, MNGIE, MTDPS1, PDECGF, TP, hPD-ECGF
• Chromosome: 22
• Chromosome location: 22q13.33
• Summary: 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 ha

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28931613	C>T	Pathogenic	Coding sequence variant, missense variant
rs121913037	C>T	Pathogenic	Coding sequence variant, missense variant
rs121913038	C>T	Pathogenic	Coding sequence variant, missense variant
rs188802138	C>T	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs199901350	G>A,T	Uncertain-significance, pathogenic	Coding sequence variant, missense variant
rs749827433	C>A,G	Pathogenic	Coding sequence variant, missense variant
rs752137335	T>G	Pathogenic	Coding sequence variant, missense variant
rs764792655	A>-	Pathogenic	Coding sequence variant, stop gained
rs767245071	C>G	Pathogenic	Splice acceptor variant
rs786205559	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs797044454	A>G,T	Pathogenic	Splice donor variant
rs863224250	C>G,T	Likely-pathogenic	Missense variant, coding sequence variant
rs863224251	T>A	Likely-pathogenic	Missense variant, coding sequence variant
rs891107196	G>T	Pathogenic	Missense variant, coding sequence variant
rs1054084896	C>A	Pathogenic	Coding sequence variant, stop gained
rs1064792857	A>C,T	Pathogenic	Coding sequence variant, missense variant
rs1064792858	G>C,T	Pathogenic	Synonymous variant, coding sequence variant, missense variant
rs1064792859	C>T	Pathogenic	Coding sequence variant, missense variant
rs1064792860	G>A	Pathogenic	Coding sequence variant, stop gained
rs1064792861	C>T	Pathogenic	Coding sequence variant, missense variant
rs1064792862	A>G	Pathogenic	Coding sequence variant, missense variant
rs1064792863	T>C	Pathogenic	Coding sequence variant, missense variant
rs1064792864	A>G	Pathogenic	Coding sequence variant, missense variant
rs1064792880	->G	Pathogenic	Frameshift variant, coding sequence variant
rs1064792886	GG>-	Pathogenic	Frameshift variant, coding sequence variant
rs1283883810	C>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT048951	hsa-miR-92a-3p	CLASH	23622248

Transcription factors

Transcription factor	Regulation	Reference
SP1	Unknown	17805539
SP3	Unknown	17805539

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001525	Process	Angiogenesis	IEA
GO:0004645	Function	1,4-alpha-oligoglucan phosphorylase activity	IEA
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005829	Component	Cytosol	IBA
GO:0005829	Component	Cytosol	TAS
GO:0006206	Process	Pyrimidine nucleobase metabolic process	IEA
GO:0006213	Process	Pyrimidine nucleoside metabolic process	IDA	1590793
GO:0006213	Process	Pyrimidine nucleoside metabolic process	IEA
GO:0006213	Process	Pyrimidine nucleoside metabolic process	IMP	9924029
GO:0006935	Process	Chemotaxis	IEA
GO:0007165	Process	Signal transduction	IEA
GO:0008083	Function	Growth factor activity	IEA
GO:0009032	Function	Thymidine phosphorylase activity	IDA	1590793
GO:0009032	Function	Thymidine phosphorylase activity	IEA
GO:0009032	Function	Thymidine phosphorylase activity	IMP	9924029
GO:0016154	Function	Pyrimidine-nucleoside phosphorylase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016757	Function	Glycosyltransferase activity	IEA
GO:0016763	Function	Pentosyltransferase activity	IEA
GO:0030154	Process	Cell differentiation	IEA
GO:0031641	Process	Regulation of myelination	IMP	9924029
GO:0042803	Function	Protein homodimerization activity	IDA	1590793
GO:0046074	Process	DTMP catabolic process	IEA
GO:0051969	Process	Regulation of transmission of nerve impulse	IMP	9924029
GO:0055086	Process	Nucleobase-containing small molecule metabolic process	IEA
GO:0072527	Process	Pyrimidine-containing compound metabolic process	IEA
GO:1901135	Process	Carbohydrate derivative metabolic process	IEA
GO:1905333	Process	Regulation of gastric motility	IMP	9924029

Other IDs

• MIM: 131222
• HGNC: 3148
• e!Ensembl: ENSG00000025708

Protein

• UniProt ID: P19971
• Protein name: Thymidine phosphorylase (TP) (EC 2.4.2.4) (Gliostatin) (Platelet-derived endothelial cell growth factor) (PD-ECGF) (TdRPase)
• Protein 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. ; C
• PDB: 1UOU, 2J0F, 2WK5, 2WK6
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02885	Glycos_trans_3N	37 → 99	Glycosyl transferase family, helical bundle domain	Domain
  PF00591	Glycos_transf_3	109 → 340	Glycosyl transferase family, a/b domain	Family
  PF07831	PYNP_C	388 → 462	Pyrimidine nucleoside phosphorylase C-terminal domain	Domain

• Sequence:

  MAALMTPGTGAPPAPGDFSGEGSQGLPDPSPEPKQLPELIRMKRDGGRLSEADIRGFVAA
  VVNGSAQGAQIGAMLMAIRLRGMDLEETSVLTQALAQSGQQLEWPEAWRQQLVDKHSTGG
  VGDKVSLVLAPALAACGCKVPMISGRGLGHTGGTLDKLESIPGFNVIQSPEQMQVLLDQA
  GCCIVGQSEQLVPADGILYAARDVTATVDSLPLITASILSKKLVEGLSALVVDVKFGGAA
  VFPNQEQARELAKTLVGVGASLGLRVAAALTAMDKPLGRCVGHALEVEEALLCMDGAGPP
  DLRDLVTTLGGALLWLSGHAGTQAQGAARVAAALDDGSALGRFERMLAAQGVDPGLARAL
  CSGSPAERRQLLPRAREQEELLAPADGTVELVRALPLALVLHELGAGRSRAGEPLRLGVG
  AELLVDVGQRLRRGTPWLRVHRDGPALSGPQSRALQEALVLSDRAPFAAPSPFAELVLPP
  QQ

• Sequence length: 482

Pathways

KEGG:

Pyrimidine metabolism
Drug metabolism - other enzymes
Metabolic pathways
Nucleotide metabolism
Bladder cancer

Reactome:

Pyrimidine salvage
Pyrimidine catabolism

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Mitochondrial DNA depletion syndrome 1	Likely pathogenic; Pathogenic	rs2148683541, rs755728248, rs1178421926, rs1027855768, rs1200609783, rs2069504242, rs1295236603, rs2522519519, rs2522551571, rs2522546758, rs2522513131, rs767575537, rs1064792855, rs1054084896, rs1064792857, rs1064792858, rs749827433, rs891107196, rs1064792860, rs1064792861, rs1064792862, rs199901350, rs1064792863, rs1064792864, rs1064792865, rs1064792866, rs121913041, rs1064792867, rs1064792868, rs1064792870, rs866001342, rs1064792872, rs121913040, rs892141220, rs1060499532, rs1060499534, rs1064792874, rs764275775, rs11479, rs1064792876, rs770277446, rs1064792877, rs1064792878, rs1064792879, rs773785934, rs1064792880, rs1064792881, rs1556486467, rs1556486029, rs1064792885, rs1064792886, rs1064792887, rs1064792888, rs1060499535, rs1064792889, rs1064792890, rs1064792891, rs1064792892, rs1213619304, rs2522546966, rs1603441843, rs2522531011, rs2069445752, rs2522531128, rs2522539725, rs2522549973, rs1603442039, rs863224255, rs121913036, rs797044454, rs121913037, rs149977726, rs786205097, rs797044455, rs786205098, rs121913038, rs28931613, rs767245071, rs121913039, rs121913042, rs2522525264, rs1250541303, rs567858165, rs2522530917, rs1556488264, rs761665644, rs1471478620, rs1180285291, rs764792655, rs1251044974, rs1203886148, rs765023287, rs761608162, rs760629248, rs1052593047, rs2069446068, rs1603442040, rs1044840059	RCV003463022 RCV003464137 RCV001783996 RCV001805744 RCV002498041 RCV003147714 RCV004571893 RCV002282855 RCV002465088 RCV002468811 RCV003147815 RCV004571218 RCV000208630 RCV000208680 RCV000208699 RCV000208614 RCV000208698 RCV000208640 RCV000208667 RCV000208694 RCV000208638 RCV000208677 RCV000208707 RCV000208704 RCV000208643 RCV000208685 RCV000208713 RCV000208641 RCV000208663 RCV000208618 RCV000208703 RCV000208700 RCV000208710 RCV000208708 RCV000208646 RCV000208689 RCV000208644 RCV000208625 RCV000208684 RCV000208621 RCV000208662 RCV000208672 RCV000208627 RCV000208670 RCV000208711 RCV000208650 RCV000208666 RCV000208709 RCV000208647 RCV000208679 RCV000208645 RCV000208688 RCV000208656 RCV000208696 RCV000208623 RCV000208695 RCV000208678 RCV000208691 RCV000208631 RCV000208673 RCV003466483 RCV003466484 RCV003464756 RCV003466485 RCV003464757 RCV003464758 RCV003466486 RCV003466487 RCV003464759 RCV003464760 RCV005030241 RCV000018133 RCV000018134 RCV000018135 RCV000018136 RCV000018137 RCV000018138 RCV000018139 RCV000018140 RCV000018141 RCV000018142 RCV000018143 RCV000018144 RCV000018145 RCV000018146 RCV004573801 RCV004573802 RCV004573803 RCV004573804 RCV000508782 RCV000508974 RCV000669866 RCV000779376 RCV002501066 RCV000855774 RCV005029567 RCV001027995 RCV005029636 RCV003467749 RCV003469279 RCV003462796 RCV003462808 RCV004570658	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Mitochondrial neurogastrointestinal encephalomyopathy	Pathogenic; Likely pathogenic	rs797044454, rs1064792878, rs121913036, rs121913037, rs149977726, rs121913038, rs767245071, rs1603441848	RCV001828033 RCV001828047 RCV001276276 RCV001276278 RCV001831582 RCV001826476 RCV001276279 RCV001825637	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Thyroid cancer, nonmedullary, 1	Likely pathogenic	rs1200609783	RCV005927726	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
TYMP-related disorder	Likely pathogenic; Pathogenic	rs1200526412, rs797044454	RCV003401967 RCV003417717	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ARTHRITIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLONIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ESOPHAGEAL SQUAMOUS CELL CARCINOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intestinal pseudo-obstruction	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MITOCHONDRIAL COMPLEX IV DEFICIENCY, NUCLEAR TYPE 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL COMPLEX IV DEFICIENCY, NUCLEAR TYPE 2	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASE	—	ClinGen, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DNA DEPLETION SYNDROME, ENCEPHALOMYOPATHIC FORM, WITH RENAL TUBULOPATHY, AUTOSOMAL RECESSIVE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL ENCEPHALOMYOPATHIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PANCREATIC NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
STOMACH NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
URINARY BLADDER NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VISCERAL MYOPATHY FAMILIAL EXTERNAL OPHTHALMOPLEGIA	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations