Human Gene ITPA (uc002wid.4) Description and Page Index
  Description: Homo sapiens inosine triphosphatase (nucleoside triphosphate pyrophosphatase) (ITPA), transcript variant 1, mRNA.
RefSeq Summary (NM_033453): This gene encodes an inosine triphosphate pyrophosphohydrolase. The encoded protein hydrolyzes inosine triphosphate and deoxyinosine triphosphate to the monophosphate nucleotide and diphosphate. This protein, which is a member of the HAM1 NTPase protein family, is found in the cytoplasm and acts as a homodimer. Defects in the encoded protein can result in inosine triphosphate pyrophosphorylase deficiency which causes an accumulation of ITP in red blood cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012].
Transcript (Including UTRs)
   Position: hg19 chr20:3,190,006-3,204,516 Size: 14,511 Total Exon Count: 8 Strand: +
Coding Region
   Position: hg19 chr20:3,190,198-3,204,108 Size: 13,911 Coding Exon Count: 8 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr20:3,190,006-3,204,516)mRNA (may differ from genome)Protein (194 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCEUniProtKB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Inosine triphosphate pyrophosphatase; Short=ITPase; Short=Inosine triphosphatase; EC=; AltName: Full=Non-canonical purine NTP pyrophosphatase; AltName: Full=Non-standard purine NTP pyrophosphatase; AltName: Full=Nucleoside-triphosphate diphosphatase; AltName: Full=Nucleoside-triphosphate pyrophosphatase; Short=NTPase; AltName: Full=Putative oncogene protein hlc14-06-p;
FUNCTION: Pyrophosphatase that hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triposphate (dHAPTP) and xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions.
CATALYTIC ACTIVITY: A nucleoside triphosphate + H(2)O = a nucleotide + diphosphate.
COFACTOR: Binds 1 magnesium ion per subunit.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.51 mM for ITP; KM=0.31 mM for dITP; KM=0.57 mM for XTP; KM=40.7 uM for dHAPTP; KM=933 uM for dGTP; Vmax=1520 umol/min/mg enzyme for ITP; Vmax=940 umol/min/mg enzyme for dITP; Vmax=1680 umol/min/mg enzyme for XTP; Note=Vmax values are similar for dITP, dHAPTP and dGTP; pH dependence: Optimum pH is 10;
SUBUNIT: Homodimer.
TISSUE SPECIFICITY: Ubiquitous. Highly expressed in heart, liver, sex glands, thyroid and adrenal gland.
DISEASE: Defects in ITPA are the cause of inosine triphosphate pyrophosphohydrolase deficiency (ITPAD) [MIM:613850]. It is a common inherited trait characterized by the abnormal accumulation of inosine triphosphate (ITP) in erythrocytes and also leukocytes and fibroblasts. The pathological consequences of ITPA deficiency, if any, are unknown. However, it might have pharmacogenomic implications and be related to increased drug toxicity of purine analog drugs. Note=Three different human populations have been reported with respect to their ITPase activity: high, mean (25% of high) and low activity. The variant Thr-32 is associated with complete loss of enzyme activity, may be by altering the local secondary structure of the protein. Heterozygotes for this polymorphism have 22.5% of the control activity: this is consistent with a dimeric structure of the enzyme.
SIMILARITY: Belongs to the HAM1 NTPase family.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): ITPA
CDC HuGE Published Literature: ITPA
Positive Disease Associations: Anemia , azathioprine tolerance , drug hypersensitivity , hepatotoxicity leukopenia , rheumatoid arthritis
Related Studies:
  1. Anemia
    Hidenori Ochi et al. Gastroenterology 2010, ITPA polymorphism affects ribavirin-induced anemia and outcomes of therapy--a genome-wide study of Japanese HCV virus patients., Gastroenterology. [PubMed 20637204]
    A missense substitution in inosine triphosphate pyrophosphatase gene affects ribavirin-induced anemia in hepatitis C virus-infected Japanese patients.
  2. azathioprine tolerance
    Marinaki, A. M. et al. 2004, Mutation in the ITPA gene predicts intolerance to azathioprine., Nucleosides, nucleotides & nucleic acids. 2004 Oct;23(9-Aug):1393-7. [PubMed 15571265]
    Polymorphism in the ITPA gene thus predicts AZA intolerance. Alternative immunosuppressive drugs, particularly 6-thioguanine, should be considered for AZA-intolerant patients with ITPase deficiency.
  3. drug hypersensitivity
    Marinaki, A. M. et al. 2004, Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase), Pharmacogenetics. 2004 Mar;14(3):181-7. [PubMed 15167706]
    Polymorphism in the ITPA gene predicts AZA intolerance. Alternative immunosuppressive drugs, particularly 6-thioguanine, should be considered for AZA-intolerant patients with ITPase deficiency.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: ITPA
Diseases sorted by gene-association score: epileptic encephalopathy, early infantile, 35* (1280), inosine triphosphate pyrophosphohydrolase deficiency* (366), itpa-related altered drug metabolism* (100), susceptibility to adverse reaction due to mercaptopurine* (25), asymptomatic neurosyphilis (11), thiopurines, poor metabolism of, 1 (10), nodular regenerative hyperplasia (8), adenosine deaminase deficiency (8), tertiary neurosyphilis (5), inflammatory bowel disease (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 29.26 RPKM in Thyroid
Total median expression: 797.98 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -88.60192-0.461 Picture PostScript Text
3' UTR -164.50408-0.403 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR002637 - Ham1p-like

Pfam Domains:
PF01725 - Ham1 family

SCOP Domains:
52972 - Maf/Ham1

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT

- X-ray MuPIT

- X-ray MuPIT

ModBase Predicted Comparative 3D Structure on Q9BY32
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserGenome BrowserGenome BrowserGenome Browser
Gene Details  Gene DetailsGene DetailsGene Details
Gene Sorter  Gene SorterGene SorterGene Sorter
  Protein SequenceProtein SequenceProtein SequenceProtein Sequence

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004551 nucleotide diphosphatase activity
GO:0016787 hydrolase activity
GO:0035529 NADH pyrophosphatase activity
GO:0035870 dITP diphosphatase activity
GO:0036220 ITP diphosphatase activity
GO:0036222 XTP diphosphatase activity
GO:0042802 identical protein binding
GO:0046872 metal ion binding
GO:0047429 nucleoside-triphosphate diphosphatase activity

Biological Process:
GO:0006193 ITP catabolic process
GO:0006195 purine nucleotide catabolic process
GO:0009117 nucleotide metabolic process
GO:0009143 nucleoside triphosphate catabolic process
GO:0051276 chromosome organization

Cellular Component:
GO:0005737 cytoplasm
GO:0005829 cytosol

-  Descriptions from all associated GenBank mRNAs
  JD125524 - Sequence 106548 from Patent EP1572962.
AF219116 - Homo sapiens inosine triphosphate pyrophosphatase (ITPA) mRNA, complete cds.
AF063607 - Homo sapiens brain my049 protein mRNA, complete cds.
JD319217 - Sequence 300241 from Patent EP1572962.
AF334680 - Homo sapiens putative oncogene GK005 mRNA, complete cds.
AB062127 - Homo sapiens OK/SW-cl.9 mRNA for inosine triphosphate pyrophosphatase, complete cds.
AK309165 - Homo sapiens cDNA, FLJ99206.
AF026816 - Homo sapiens putative oncogene protein hlc14-06-p mRNA, complete cds.
EF199841 - Homo sapiens inosine triphosphate pyrophosphatase transcript variant I mRNA, complete cds.
EF213026 - Homo sapiens inosine triphosphate pyrophosphatase transcript variant II (ITPA) mRNA, complete cds, alternatively spliced.
BC010138 - Homo sapiens inosine triphosphatase (nucleoside triphosphate pyrophosphatase), mRNA (cDNA clone MGC:19624 IMAGE:4124624), complete cds.
LF348273 - JP 2014500723-A/155776: Polycomb-Associated Non-Coding RNAs.
DQ896125 - Synthetic construct Homo sapiens clone IMAGE:100010585; FLH190540.01L; RZPDo839B0666D inosine triphosphatase (nucleoside triphosphate pyrophosphatase) (ITPA) gene, encodes complete protein.
EU176384 - Synthetic construct Homo sapiens clone IMAGE:100006492; FLH190547.01X; RZPDo839B01252D inosine triphosphatase (nucleoside triphosphate pyrophosphatase) (ITPA) gene, encodes complete protein.
KU178148 - Homo sapiens inosine triphosphatase isoform 1 (ITPA) mRNA, partial cds.
KU178149 - Homo sapiens inosine triphosphatase isoform 2 (ITPA) mRNA, partial cds, alternatively spliced.
GQ891343 - Homo sapiens clone HEL-S-114d epididymis secretory sperm binding protein mRNA, complete cds.
LF348272 - JP 2014500723-A/155775: Polycomb-Associated Non-Coding RNAs.
LF348271 - JP 2014500723-A/155774: Polycomb-Associated Non-Coding RNAs.
JD526594 - Sequence 507618 from Patent EP1572962.
JD158097 - Sequence 139121 from Patent EP1572962.
JD261244 - Sequence 242268 from Patent EP1572962.
JD271166 - Sequence 252190 from Patent EP1572962.
JD525744 - Sequence 506768 from Patent EP1572962.
MA583850 - JP 2018138019-A/155776: Polycomb-Associated Non-Coding RNAs.
MA583849 - JP 2018138019-A/155775: Polycomb-Associated Non-Coding RNAs.
MA583848 - JP 2018138019-A/155774: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00230 - Purine metabolism
hsa00240 - Pyrimidine metabolism
hsa00983 - Drug metabolism - other enzymes
hsa01100 - Metabolic pathways

Reactome (by CSHL, EBI, and GO)

Protein Q9BY32 (Reactome details) participates in the following event(s):

R-HSA-2509827 ITPA hydrolyses ITP to IMP
R-HSA-2509838 ITPA hydrolyses dITP to dIMP
R-HSA-2509831 ITPA hydrolyses XTP to XMP
R-HSA-74259 Purine catabolism
R-HSA-8956319 Nucleobase catabolism
R-HSA-15869 Metabolism of nucleotides
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: A4UIM5, B2BCH7, C20orf37, ITPA_HUMAN, My049, NM_033453, NP_258412, O14878, OK/SW-cl.9, Q5JWH4, Q9BY32, Q9BYN1, Q9BYX0, Q9H3H8, uc002wid.3
UCSC ID: uc002wid.4
RefSeq Accession: NM_033453
Protein: Q9BY32 (aka ITPA_HUMAN)
CCDS: CCDS13051.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_033453.3
exon count: 8CDS single in 3' UTR: no RNA size: 1202
ORF size: 585CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1362.00frame shift in genome: no % Coverage: 98.59
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.