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Set Analyses:

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ITPA Gene

protein-coding GIFtS: 71
GCID: GC20P003189

Inosine Triphosphatase (Nucleoside Triphosphate Pyrophosphatase)

(Previous symbol: C20orf37)

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Inosine Triphosphatase (Nucleoside Triphosphate Pyrophosphatase)¹ ²		HLC14-06-P²
C20orf37¹ ² ³		dJ794I6.3²
Non-Canonical Purine NTP Pyrophosphatase² ³		Inosine Triphosphatase-A²
Non-Standard Purine NTP Pyrophosphatase² ³		Inosine Triphosphate Pyrophosphatase²
Nucleoside-Triphosphate Diphosphatase² ³		Inosine Triphosphate Pyrophosphohydrolase²
Putative Oncogene Protein Hlc14-06-P² ³		Inosine Triphosphatase³
ITPase² ³		Nucleoside-Triphosphate Pyrophosphatase³
NTPase² ³		EC 3.6.1⁸
EC 3.6.1.19³ ⁸

External Ids:	HGNC: 6176¹	Entrez Gene: 3704²	Ensembl: ENSG00000125877⁷	OMIM: 147520⁵	UniProtKB: Q9BY32³

Export aliases for ITPA gene to outside databases

Previous GC identifers: GC20P003178 GC20P003185 GC20P003138

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for ITPA Gene:

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)

GeneCards Summary for ITPA Gene:

ITPA (inosine triphosphatase (nucleoside triphosphate pyrophosphatase)) is a protein-coding gene. Diseases associated with ITPA include leukopenia, and inosine triphosphate pyrophosphohydrolase deficiency. GO annotations related to this gene include nucleotide binding.

UniProtKB/Swiss-Prot: ITPA_HUMAN, Q9BY32

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

Gene Wiki entry for ITPA Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:

NC_000020.11 NT_011387.9 NC_018931.2

Regulatory elements:

Regulatory transcription factor binding sites in the ITPA gene promoter:
AhR Max1 USF1 AML1a MIF-1 Arnt USF-1 Sox9 c-Myb c-Myc
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: ITPA promoter sequence

Search Chromatin IP Primers for ITPA

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ITPA

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20p Ensembl cytogenetic band: 20p13 HGNC cytogenetic band: 20p

ITPA Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ITPA gene location

GeneLoc information about chromosome 20 GeneLoc Exon Structure

GeneLoc location for GC20P003189: view genomic region (about GC identifiers)

Start:	3,189,514 bp from pter	End:	3,204,516 bp from pter
Size:	15,003 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: ITPA_HUMAN, Q9BY32 (See protein sequence)

Recommended Name: Inosine triphosphate pyrophosphatase

Size: 194 amino acids; 21446 Da

Cofactor: Binds 1 magnesium ion per subunit

Subunit: Homodimer

4 PDB 3D structures from and Proteopedia for ITPA:

2CAR (3D)

2I5D (3D)

2J4E (3D)

4F95 (3D)

Secondary accessions: A2A2N2 A4UIM5 B2BCH7 O14878 Q5JWH4 Q9BYN1 Q9BYX0 Q9H3H8

Alternative splicing: 3 isoforms: Q9BY32-1 Q9BY32-2 Q9BY32-3 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for ITPA: NX_Q9BY32

Explore proteomics data for ITPA at MOPED

Post-translational modifications:

Ubiquitination² at Lys9, Lys96

Modification sites at PhosphoSitePlus

3 DME Specific Peptides for ITPA (Q9BY32)

KIVFVTGN

GPVLVEDTCLCFNAL

KKIVFVTGNAKKLEE

See ITPA Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins (3 alternative transcripts):

NP_001254552.1 NP_258412.1 NP_852470.1

ENSEMBL proteins:

ENSP00000369456 ENSP00000413282 ENSP00000382732

Reactome Protein details: Q9BY32

ITPA Human Recombinant Protein Products:

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	Novus Biologicals ITPA Proteins Novus Biologicals ITPA Lysate
	Browse Sino Biological Recombinant Proteins Browse Sino Biological Cell Lysates
	ProSpec Recombinant Protein for ITPA
	Cloud-Clone Corp. Proteins for ITPA

ITPA Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of ITPA
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	Novus Biologicals ITPA Antibodies
	Abcam antibodies for ITPA
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	ThermoFisher Antibody for ITPA
	LSBio Antibodies in human, mouse, rat for ITPA

ITPA Assay Products:

	Browse Kits and Assays available from EMD Millipore
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	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for ITPA
	Browse Enzo Life Sciences for kits & assays
	Cloud-Clone Corp. ELISAs for ITPA Cloud-Clone Corp. CLIAs for ITPA

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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2 InterPro protein domains:

IPR027502 ITPase

IPR002637 Ham1p-like

Graphical View of Domain Structure for InterPro Entry Q9BY32

ProtoNet protein and cluster: Q9BY32

1 Blocks protein domain: IPB002637 Ham1-like protein

UniProtKB/Swiss-Prot: ITPA_HUMAN, Q9BY32

Similarity: Belongs to the HAM1 NTPase family

ITPA for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: ITPA_HUMAN, Q9BY32

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

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;

Genatlas biochemistry entry for ITPA:

inosine triphosphatase (nucleoside triphosphate pyrophosphatase)

Enzyme Numbers (IUBMB): EC 3.6.1.19¹ ² EC 3.6.1²

Gene Ontology (GO): Selected molecular function terms (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000166	nucleotide binding	IEA	--
GO:0016787	hydrolase activity	--	--
GO:0035870	dITP diphosphatase activity	EXP	--
GO:0036220	ITP diphosphatase activity	EXP	--
GO:0036222	XTP diphosphatase activity	EXP	--

ITPA for ontologies About GeneDecksing

Phenotypes:
1 GenomeRNAi human phenotype for ITPA:

Increased gamma-H2AX phosphory

10 MGI mutant phenotypes (inferred from 1 allele) (MGI details for Itpa):

behavior/neurological	cardiovascular system	cellular	growth/size/body	hematopoietic system
integument	mortality/aging	muscle	reproductive system	respiratory system

ITPA for phenotypes About GeneDecksing

Animal Models:
MGI mouse knock-out Itpa^tm1Skmi for ITPA

inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for ITPA

inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for ITPA

genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for ITPA

genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for ITPA

miRNA Products:		miRTarBase miRNAs that target ITPA: hsa-mir-93-5p (MIRT048752)

		Block miRNA regulation of human, mouse, rat ITPA using miScript Target Protectors
		2 qRT-PCR Assays for microRNAs that regulate ITPA:
		hsa-miR-2355-5p hsa-miR-1252
		SwitchGear 3'UTR luciferase reporter plasmid: ITPA 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for ITPA
		Predesigned siRNA for gene silencing in human, mouse, rat ITPA

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for ITPA

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		GenScript: all cDNA clones in your preferred vector (see all 2): ITPA (NM_033453)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for ITPA
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ITPA

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for ITPA
		Browse ESI BIO Cell Lines and PureStem Progenitors for ITPA

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ITPA

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

ITPA_HUMAN, Q9BY32: Cytoplasm

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
cytosol	4
extracellular	2
mitochondrion	2
cytoskeleton	1
nucleus	1

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Gene Ontology (GO): 2 cellular component terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005737	cytoplasm	--	--
GO:0005829	cytosol	TAS	--

ITPA for ontologies About GeneDecksing

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for ITPA About

See pathways by source

SuperPath

Contained pathways About

Purine metabolism (KEGG)

	Purine metabolism	0.38			ATP ITP metabolism	0.31
	Pyrimidine metabolism	0.38

Metabolism

Metabolism

0.38

Metabolic pathways

0.38

Purine metabolism (REACTOME)

Metabolism of nucleotides

0.42

Glucuronidation

Drug metabolism - other enzymes

0.36

One carbon pool by folate

Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics

0.34

Pathways by source See SuperPaths
Show all pathways

1 GeneGo (Thomson Reuters) Pathway for ITPA

ATP/ITP metabolism

1 Reactome Pathway for ITPA

Metabolism of nucleotides

1 PharmGKB Pathway for ITPA

Thiopurine Pathway, Pharmacokinetics/Pharmacodynamics

4 Kegg Pathways (Kegg details for ITPA):

	Purine metabolism
	Pyrimidine metabolism
	Drug metabolism - other enzymes
	Metabolic pathways

ITPA for pathways About GeneDecksing

Custom Pathway & Disease-focused RT² Profiler PCR Arrays for ITPA
Interactions:

GeneGlobe Interaction Network for ITPA

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for ITPA (Q9BY32³ ENSP00000369456⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 181)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
ATP6V1B2	P21281³, ENSP00000276390⁴	I2D: score=4 STRING: ENSP00000276390
RUVBL1	Q9Y265³, ENSP00000318297⁴	I2D: score=1 STRING: ENSP00000318297
CAD	P27708³, ENSP00000264705⁴	I2D: score=1 STRING: ENSP00000264705
HSP90AA1	P07900³	I2D: score=3
RPS24	P62847³	I2D: score=2

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Gene Ontology (GO): 5 biological process terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006193	ITP catabolic process	IEA	--
GO:0009204	deoxyribonucleoside triphosphate catabolic process	IEA	--
GO:0044281	small molecule metabolic process	TAS	--
GO:0051276	chromosome organization	IEA	--
GO:0055086	nucleobase-containing small molecule metabolic process	TAS	--

ITPA for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Browse Tocris compounds for ITPA

Selected HMDB Compounds for ITPA (see all 24) About this table

Compound	Synonyms	CAS #	PubMed Ids
2'-Deoxyguanosine 5'-monophosphate	2'-Deoxy-5'-GMP (see all 21)	902-04-5	--
2'-Deoxyinosine triphosphate	2'-Deoxyinosine-5'-triphosphate (see all 6)	16595-02-1	--
Adenosine triphosphate	5'-(tetrahydrogen triphosphate) Adenosine (see all 24)	56-65-5	--
Cytidine triphosphate	cytidine 5'-(tetrahydrogen triphosphate) (see all 15)	65-47-4	--
Deoxyuridine triphosphate	2'-Deoxyuridine-5'-triphosphorate (see all 9)	1173-82-6	--
Guanosine monophosphate	5'-GMP (see all 14)	85-32-5	--
Guanosine triphosphate	5'-GTP (see all 10)	86-01-1	--
Inosine triphosphate	inosine 5'-(tetrahydrogen triphosphate) (see all 13)	132-06-9	--
Inosinic acid	5'-IMP (see all 9)	131-99-7	--
Magnesium	Magnesium (see all 2)	7439-95-4	--

1 DrugBank Compound for ITPA About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Citric Acid	--	77-92-9	target	--	10592235

Selected Novoseek inferred chemical compound relationships for ITPA gene (see all 15) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
inosine triphosphate	99.3	142	17697207 (4), 11278832 (3), 15167706 (2), 15243983 (2) (see all 43)
thiopurine	96	63	17697198 (6), 19960028 (3), 16431304 (2), 18223458 (2) (see all 28)
xanthosine 5'-triphosphate	92.5	5	16384889 (1), 9337071 (1), 18600522 (1)
6 mercaptopurine	87.2	30	18685564 (5), 20021291 (3), 15571266 (1), 19151640 (1) (see all 8)
inosine	77.9	23	17138556 (4), 17924837 (2), 18223458 (2), 18616518 (1) (see all 10)
inosine monophosphate	77.8	12	16384889 (1), 20205660 (1), 18062990 (1), 15946879 (1) (see all 7)
azathioprine	72.3	22	15167706 (4), 16611274 (4), 16431304 (3), 15973722 (3) (see all 8)
azathioprine	70.1	19	19229528 (4), 19214663 (3), 20367526 (3), 18090994 (1) (see all 7)
6 thioguanine	64.1	3	15167706 (1), 16918876 (1), 15571265 (1)
pyrophosphate	44.6	3	15946879 (1), 19914375 (1)

4 PharmGKB related drug/compound annotations for ITPA gene About this table

Drug/compound	PharmGKB Annotation
interferon alfa-2b, recombinant	CA
azathioprine	CA
methotrexate	CA
ribavirin	CA

ITPA for compounds About GeneDecksing

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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REFSEQ mRNAs for ITPA gene (3 alternative transcripts):

NM_001267623.1 NM_033453.3 NM_181493.2

Unigene Cluster for ITPA:

Inosine triphosphatase (nucleoside triphosphate pyrophosphatase)

Hs.415299 [show with all ESTs]

Unigene Representative Sequence: BM918059

10 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000483354 ENST00000460676 ENST00000380113(uc002wie.3 uc002wid.3)

ENST00000490838(uc002wif.3) ENST00000609835 ENST00000455664 ENST00000460550

ENST00000399838 ENST00000461029 ENST00000472295

Congresses - knowledge worth sharing:
European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 10 - 13 May 2014

miRNA Products:		Block miRNA regulation of human, mouse, rat ITPA using miScript Target Protectors
		2 qRT-PCR Assays for microRNAs that regulate ITPA:
		hsa-miR-2355-5p hsa-miR-1252
		SwitchGear 3'UTR luciferase reporter plasmid: ITPA 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for ITPA
		Predesigned siRNA for gene silencing in human, mouse, rat ITPA

Clone Products:		OriGene clones in human, mouse for ITPA (see all 11) OriGene ORF clones in mouse, rat for ITPA OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 2): ITPA (NM_033453)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for ITPA
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ITPA

Primer Products:		OriGene qPCR primer pairs and template standards for ITPA OriGene qSTAR qPCR primer pairs in human, mouse for ITPA
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat ITPA
		QuantiTect SYBR Green Assays in human, mouse, rat ITPA
		QuantiFast Probe-based Assays in human, mouse, rat ITPA

Additional mRNA sequence:

AB062127.1 AF026816.2 AF063607.1 AF219116.1 AF334680.1 AK309165.1 BC010138.2 EF199841.1

EF213026.1 NR_052000.1 NR_052001.1 NR_052002.1

15 DOTS entries:

DT.100802896 DT.452584 DT.92434627 DT.100802893 DT.40253236 DT.40305266 DT.92434612 DT.92434616

DT.100802901 DT.91934045 DT.92434624 DT.95332879 DT.95341588 DT.40193344 DT.431898

11 AceView cDNA sequences:

NM_033453 BC010138 CR591168 CR607092 NM_181493 CR595616 AF026816 AB062127

AF219116 AF063607 AF334680

GeneLoc Exon Structure

Selected Alternative Splicing Database (ASD) splice patterns (SP) for ITPA (see all 9) About this scheme

ExUns:	1	^	2a	·	2b	·	2c	·	2d	·	2e	·	2f	^	3	^	4a	·	4b	^	5	^	6	^	7	^	8a	·	8b	^	9a	·	9b	·	9c	·	9d	·	9e	·	9f
SP1:																	-										-
SP2:											-		-				-										-
SP3:													-				-										-
SP4:											-		-		-												-
SP5:																	-		-								-

ECgene alternative splicing isoforms for ITPA

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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ITPA expression in normal human tissues (normalized intensities) ITPA embryonic expression: see
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: GTTTTTAAAT

About this image

ITPA expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 4) fully expand


Brain (Nervous System) fully expand to see all 7 entries
Cerebral Cortex

Testis (Reproductive System)
Leydig Cells Testis Interstitium

Liver (Hepatobiliary System)
Hepatocytes Liver Lobule

Neural Tube (Nervous System)
Telencephalon

ITPA Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

ITPA Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.415299

UniProtKB/Swiss-Prot: ITPA_HUMAN, Q9BY32

Tissue specificity: Ubiquitous. Highly expressed in heart, liver, sex glands, thyroid and adrenal gland

Custom PCR Arrays for ITPA

Primer Products:		OriGene qPCR primer pairs and template standards for ITPA OriGene qSTAR qPCR primer pairs in human, mouse for ITPA
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat ITPA
		QuantiTect SYBR Green Assays in human, mouse, rat ITPA
		QuantiFast Probe-based Assays in human, mouse, rat ITPA

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ITPA

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of eukaryotes.

Orthologs for ITPA gene from Selected species (see all 26) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Itpa^{1 , 5}	inosine triphosphatase (nucleoside triphosphate pyrophosphatase)^{1, 5}	85.66(n)¹ 90.67(a)¹		2 (63.24 cM)⁵ 16434¹ NM_025922.2¹ NP_080198.2¹ 130667610⁵
chicken (Gallus gallus)	Aves	ITPA¹	inosine triphosphatase (nucleoside triphosphate pyrophosphatase)	74.87(n) 78.07(a)		424390 NM_001271930.1 NP_001258859.1
lizard (Anolis carolinensis)	Reptilia	ITPA⁶	inosine triphosphatase (nucleoside triphosphate py...	65(a)	1 ↔ 1	GL343300.1(1183563-1192305)
African clawed frog (Xenopus laevis)	Amphibia	Xl.10054²	Xenopus laevis transcribed sequence with moderate similarity more	76.38(n)		BU907998.1
zebrafish (Danio rerio)	Actinopterygii	itpa¹	inosine triphosphatase (nucleoside triphosphate pyrophosphatase)	68.12(n) 74.86(a)		557834 XM_005160446.1 XP_005160503.1
fruit fly (Drosophila melanogaster)	Insecta	CG8891^{1 , 3}	CG8891¹	66(a)³ 66.3(n)¹ 67.21(a)¹		33718¹ NM_135046.5¹ NP_608890.1¹
worm (Caenorhabditis elegans)	Secernentea	hap-1^{1 , 3}	hap-1¹	61(a)³ 58.24(n)¹ 62.92(a)¹		III(5335392-5336749)³ 175724¹ NM_065720.3¹ NP_498121.1¹
baker's yeast (Saccharomyces cerevisiae)	Saccharomycetes	HAM1(YJR069C)⁴	Conserved protein with deoxyribonucleoside triphosphate more	--		10(569399-568806) 853532 NP_012603.1
thale cress (Arabidopsis thaliana)	eudicotyledons	AT4G13720¹	AT4G13720	60.36(n) 61.62(a)		827006 NM_117446.2 NP_567410.1
rice (Oryza sativa)	Liliopsida	Os.46595²	Oryza sativa (japonica cultivar-group) cDNA clone0 more	74.1(n)		AK059744.1

ENSEMBL Gene Tree for ITPA (if available)
TreeFam Gene Tree for ITPA (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 20 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs1127354^1,2,,4	C,F	Inosine triphosphate pyrophosphohydrolase deficiency (ITPAD)⁴ pathogenic¹	3137448(+)	`AGTTTA/C/G/T CATGC`	8	T P	mis¹ int¹		13		MN NS EA CSA WA NA EU	7326
rs145254749^1,2	C	--	3131125(+)	`TTAACC/GAGGCA`	1	--	us2k¹		0	--	--	--	--
rs181482500^1,2		--	3131207(+)	`GAGGTC/TGCAGT`	1	--	us2k¹		0	--	--	--	--
rs186596444^1,2		--	3131214(+)	`CAGTGA/TGCCGG`	1	--	us2k¹		0	--	--	--	--
rs66696167^1,2	C,F	--	3131218(+)	`GAGCCG/AGGACC`	1	--	us2k¹		7		NA WA EA	366
rs149180648^1,2		--	3131296(+)	`AATGAA/GAAAGA`	1	--	us2k¹		0	--	--	--	--
rs6139030^1,2	C,F,H	--	3131342(+)	`TGTGAT/CCTTTT`	1	--	us2k¹		17		NS EA NA CSA WA	2340
rs111386206^1,2	C,F	--	3131383(+)	`CTCACG/ATCACC`	1	--	us2k¹		1		NA	2
rs116936000^1,2	C,F	--	3131630(+)	`CCTACT/CATGTA`	4	--	us2k¹		1		EA	120
rs143342837^1,2		--	3131667(+)	`GGTGAA/GGCTGG`	4	--	us2k¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for ITPA (3189514 - 3204516 bp)

Structural Variations
Database of Genomic Variants (DGV) 5 variations for ITPA: About this table

Variant ID	Type	Subtype	PubMed ID
dgv4520n71	CNV	Loss	21882294
nsv912604	CNV	Loss	21882294
dgv4519n71	CNV	Loss	21882294
nsv528355	CNV	Loss	19592680
nsv833898	CNV	Gain+Loss	17160897

Human Gene Mutation Database (HGMD): ITPA

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing ITPA

DNA2.0 Custom Variant and Variant Library Synthesis for ITPA

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 147520
OMIM disorders: 613850
UniProtKB/Swiss-Prot: ITPA_HUMAN, Q9BY32

Inosine triphosphate pyrophosphohydrolase deficiency (ITPAD) [MIM:613850]: A common inherited condition

characterized by the abnormal accumulation of inosine triphosphate in erythrocytes. It might have pharmacogenomic

implications and be related to increased drug toxicity of purine analog drugs. Note=The disease is caused by

mutations affecting the gene represented in this entry. 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

Selected diseases for ITPA (see all 33): About MalaCards

leukopenia inosine triphosphate pyrophosphohydrolase deficiency nodular regenerative hyperplasia adenosine deaminase deficiency

interstitial lung disease pancytopenia langerhans-cell histiocytosis histiocytosis

inflammatory bowel disease thrombocytosis hemolytic anemia labyrinthitis

thrombocytopenia crohn's disease hepatitis c virus hepatitis c

lymphoblastic leukemia systemic lupus erythematosus pneumonia lupus erythematosus

3 diseases from the University of Copenhagen DISEASES database for ITPA:

Hepatitis C Anemia Inflammatory bowel disease

ITPA for disorders About GeneDecksing

6 Novoseek inferred disease relationships for ITPA gene About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
inflammatory bowel diseases	71.4	9	16611274 (2), 17697198 (2), 15167706 (1), 19960028 (1) (see all 6)
enzyme deficiency	56.8	2	17304144 (1)
leukopenia	45.5	2	19229528 (1), 17697207 (1)
colitis ulcerative	37.2	1	17697207 (1)
pancreatitis	32.6	2	15564886 (1)
hyperplasia	10.4	1	18090994 (1)

Genetic Association Database (GAD): ITPA
Human Genome Epidemiology (HuGE) Navigator: ITPA (40 documents)

Export disorders for ITPA gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for ITPA gene, integrated from 10 sources (see all 119):
(articles sorted by number of sources associating them with ITPA)

Utopia: connect your pdf to the dynamic
world of online information

Cloning, expression, and characterization of a human inosine triphosphate pyrophosphatase encoded by the ITPA gene. (PubMed id 11278832)^{1, 2, 3, 9} Lin S.... Mao Y. (J. Biol. Chem. 2001)
DNA polymorphisms in ITPA including basis of inosine triphosphatase deficiency. (PubMed id 12436200)^{1, 2, 4, 9} Cao H. and Hegele R.A. (J. Hum. Genet. 2002)
Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency. (PubMed id 12384777)^{1, 2, 9} Sumi S.... Duley J.A. (Hum. Genet. 2002)
Adverse drug reactions to azathioprine therapy are associated with polymorphism in the gene encoding inosine triphosphate pyrophosphatase (ITPase). (PubMed id 15167706)^{1, 4, 9} Marinaki A.M....Sanderson J.D. (Pharmacogenetics 2004)
Genetic polymorphism of inosine triphosphate pyrophosphatase is a determinant of mercaptopurine metabolism and toxicity during treatment for acute lymphoblastic leukemia. (PubMed id 18685564)^{1, 4, 9} Stocco G....Evans W.E. (Clin. Pharmacol. Ther. 2009)
Crystal structure of human inosine triphosphatase. Substrate binding and implication of the inosine triphosphatase deficiency mutation P32T. (PubMed id 17138556)^{1, 2, 9} Stenmark P.... Schueler H. (J. Biol. Chem. 2007)
Meta-analysis: Inosine triphosphate pyrophosphatase polymorphisms and thiopurine toxicity in the treatment of inflammatory bowel disease. (PubMed id 17697198)^{1, 4, 9} Van Dieren J.M....Van der Woude C.J. (amp 2007)
Analysis of ITPA phenotype-genotype correlation in the Bulgarian population revealed a novel gene variant in exon 6. (PubMed id 17304144)^{1, 4, 9} Atanasova S....von Ahsen N. (Ther Drug Monit 2007)
Genetic basis of inosine triphosphate pyrophosphohydrolase deficiency in the Japanese population. (PubMed id 15946879)^{1, 4, 9} Maeda T.... Togari H. (Mol. Genet. Metab. 2005)
TPMT but not ITPA gene polymorphism influences the risk of azathioprine intolerance in renal transplant recipients. (PubMed id 19229528)^{1, 4, 9} Kurzawski M....Drozdzik M. (Eur. J. Clin. Pharmacol. 2009)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 3704	HGNC: 6176	AceView: ITPA	Ensembl:ENSG00000125877	euGenes: HUgn3704
ECgene: ITPA	Kegg: 3704	H-InvDB: ITPA

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for ITPA	Pharmacogenomics, SNPs, Pathways

Intellectual Property for ITPA gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for ITPA gene:
Search GeneIP for patents involving ITPA

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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Inosine Triphosphatase (Nucleoside Triphosphate Pyrophosphatase)

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Inosine Triphosphatase (Nucleoside Triphosphate Pyrophosphatase)

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