{{Rsnum
|rsid=1127354
|Gene=ITPA
|Chromosome=20
|position=3213196
|Orientation=plus
|ReferenceAllele=C
|MissenseAllele=A
|GMAF=0.08081
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;C)
|geno3=(C;C)
|Gene_s=ITPA
}}[[rs1127354]] (Pro32Thr/P32T, 94C>A) is a SNP within the [[ITPA]] (Inosine triphosphate pyrophosphatase) gene.

{{PMID|18685564|OA=1
}} (note: [[rs1127354]] supersedes [[rs41320251]]) abolishes IPTA activity in homozygous individuals and reduces the activity to 25% in heterozygous subjects, [[mercaptopurine]] metabolism (sig. higher methyl mercaptopurine nucleotides levels + higher probability of severe febrile neutropenia in A carriers treated with mercaptopurine)

{{omim
|desc=INOSINE TRIPHOSPHATASE DEFICIENCY
|id=147520
|rsnum=1127354
|variant=0001
}}

{{PharmGKB
|RSID=rs1127354
|Name_s=ITPA: 94C>A; P32T
|Gene_s=ITPA
|Feature=Exon/NonSyn
|Evidence=PubMed ID:19129747
|Annotation=This polymorphism in the ITPA gene had the highest correlation with the change in SLE disease activity index score (r = 0.354, P = 0.006).
|Drugs=azathioprine
|Drug Classes=
|Diseases=Lupus Erythematosus, Systemic
|Curation Level=Curated
|PharmGKB Accession ID=PA164833194
}}
{{PMID Auto
|PMID=20021291
|Title=Genetic polymorphism of inosine-triphosphate-pyrophosphatase influences mercaptopurine metabolism and toxicity during treatment of acute lymphoblastic leukemia individualized for thiopurine-S-methyl-transferase status
}}

{{PMID Auto
|PMID=20637204
|Title=ITPA Polymorphism Affects Ribavirin-induced Anemia and Outcome of Therapy - a Genome-wide Study of Japanese HCV Patients
}}

{{PharmGKB
|RSID=rs1127354
|Name_s=ITPA
|Gene_s=ITPA
|Feature=Exon/NonSyn
|Evidence=PubMed ID:18685564
|Annotation=A study has shown that this SNP (rs41320251) in ITPA gene is a significant determinant of mercaptopurine metabolism and of neutropenia during treatment in patients with acute lymphoblastic leukemia treated with combination chemotherapy.
|Drugs=mercaptopurine
|Drug Classes=
|Diseases=Precursor Cell Lymphoblastic Leukemia-Lymphoma
|Curation Level=Curated
|PharmGKB Accession ID=PA162427747
}}

{{PharmGKB
|RSID=rs1127354
|Name_s=
|Gene_s=ITPA
|Feature=Exon/NonSyn
|Evidence=PubMed ID:18685564
|Annotation=In a study in children with acute lymphoblastic leukemia (ALL), this variant in the ITPA gene was a significant determinant of mercaptopurine metabolism and of severe febrile neutropenia, after combination chemotherapy in which mercaptopurine doses were individualized on the basis of TPMT genotype.
|Drugs=mercaptopurine
|Drug Classes=
|Diseases=
|Curation Level=Curated
|PharmGKB Accession ID=PA162372602
}}
{{PMID Auto
|PMID=21246582
|Title=Influence of ITPA polymorphisms on decreases of hemoglobin during treatment with pegylated interferon, ribavirin, and telaprevir
}}

{{PMID Auto
|PMID=21274861
|Title=Inosine triphosphatase genetic variants are protective against anemia during antiviral therapy for HCV2/3 but do not decrease dose reductions of RBV or increase SVR
}}

{{PMID Auto
|PMID=21628662
|Title=IL28B But Not ITPA Polymorphism Is Predictive of Response to Pegylated Interferon, Ribavirin, and Telaprevir Triple Therapy in Patients With Genotype 1 Hepatitis C
|OA=1
}}

{{PMID Auto
|PMID=21659334
|Title=Genome-wide association study identified ITPA/DDRGK1 variants reflecting thrombocytopenia in pegylated interferon and ribavirin therapy for chronic hepatitis C
}}

{{ population diversity
| geno1 = (A;A)
| geno2 = (A;C)
| geno3 = (C;C)
| CEU | 0.0 | 16.7 | 83.3
| CHB | 4.4 | 13.3 | 82.2
| JPT | 0.0 | 20.0 | 80.0
| YRI | 0.0 | 6.7 | 93.3
}}
{{PMID Auto
|PMID=22052220
|Title=Polymorphism of the inosine triphosphate pyrophosphatase gene predicts             ribavirin-induced anemia in chronic hepatitis C patients
}}

{{PMID Auto
|PMID=22118055
|Title=Single and combined IL28B, ITPA and SLC28A3 host genetic markers modulating response to anti-hepatitis C therapy
}}

{{PMID Auto
|PMID=22460221
|Title=Anemia and thrombocytosis induced by ribavirin monotherapy in patients with chronic hepatitis C
}}

{{PMID Auto
|PMID=22571903
|Title=Gene expression profiles associated with anaemia and ITPA genotypes in patients with chronic hepatitis C (CH-C)
}}

{{PMID Auto
|PMID=21703177
|Title=Genome-wide association study of interferon-related cytopenia in chronic hepatitis C patients
|OA=1
}}

{{ClinVar
|rsid=1127354
|Reversed=0
|FwdREF=C
|FwdALT=A,G,T
|REF=C
|ALT=A,G,T
|RSPOS=3193842
|CHROM=20
|GMAF=0.0806
|dbSNPBuildID=86
|SSR=0
|SAO=1
|VP=0x050378000000150516130100
|GENEINFO=ITPA:3704
|GENE_NAME=ITPA
|GENE_ID=3704
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000020.10:g.3193842C>A
|CLNSRC=OMIM Allelic Variant
|CLNORIGIN=0
|CLNSRCID=147520.0001
|CLNSIG=5
|CLNCUI=C1840173
|CLNDBN=Inosine triphosphatase deficiency
|Disease=Inosine triphosphatase deficiency
|CLNACC=RCV000015867.24
|Tags=PM;TPA;PMC;S3D;SLO;VLD;G5;HD;GNO;KGPhase1;KGPROD;OTHERKG;LSD;MTP;OM
|CAF=0.9192; 0.08081; .
|CLNDSDB=MedGen:OMIM
|CLNDSDBID=C1840173:613850
|COMMON=1
}}

{{PMID|17186469|OA=1
}} Mutations in the gene encoding the Wnt-signaling component R-spondin 4 (RSPO4) cause autosomal recessive anonychia.

{{PMID|18662289|OA=1
}} Pharmacogenomic studies of the anticancer and immunosuppressive thiopurines mercaptopurine and azathioprine.

{{PMID|19193698|OA=1
}} Investigation of candidate polymorphisms and disease activity in rheumatoid arthritis patients on methotrexate.

{{PMID|20547162|OA=1
}} Variants in the ITPA gene protect against ribavirin-induced hemolytic anemia and decrease the need for ribavirin dose reduction.

{{PMID|20977565}} ITPA gene variant protects against anemia induced by pegylated interferon-alpha and ribavirin therapy for Japanese patients with chronic hepatitis C.

{{PMID|21503919}} Common genetic polymorphism of ITPA gene affects ribavirin-induced anemia and effect of peg-interferon plus ribavirin therapy.

{{PMID|22028438}} Impact of inosine triphosphatase gene variants on the risk of anemia in HIV/hepatitis C virus-coinfected patients treated for chronic hepatitis C.

{{PMID|22158703|OA=1
}} Variants in the ITPA gene protect against ribavirin-induced hemolytic anemia in HIV/HCV-coinfected patients with all HCV genotypes.

{{PMID|22181672}} Efficacy of splenectomy in preventing anemia in patients with recurrent hepatitis C following liver transplantation is not dependent on inosine triphosphate pyrophosphatase genotype.

{{PMID|22406654}} Inosine triphosphatase polymorphisms and ribavirin pharmacokinetics as determinants of ribavirin-associate anemia in patients receiving standard anti-HCV treatment.

{{PMID|22430973|OA=1
}} Association of ITPA gene polymorphisms and the risk of ribavirin-induced anemia in HIV/hepatitis C virus (HCV)-coinfected patients receiving HCV combination therapy.

{{PMID|22613675}} Comparison of three different methods for the evaluation of IL28 and ITPA polymorphisms in patients infected with HCV.

{{GET Evidence
|gene=ITPA
|aa_change=Pro32Thr
|aa_change_short=P32T
|impact=pharmacogenetic
|qualified_impact=Low clinical importance,  pharmacogenetic
|inheritance=recessive
|quality_scores=Array
|dbsnp_id=rs1127354
|overall_frequency_n=656
|overall_frequency_d=10758
|overall_frequency=0.0609779
|n_genomes=7
|n_genomes_annotated=0
|n_haplomes=7
|n_articles=6
|n_articles_annotated=6
|qualityscore_in_silico=2
|qualitycomment_in_silico=Y
|qualityscore_in_vitro=2
|qualitycomment_in_vitro=Y
|qualityscore_case_control=5
|qualitycomment_case_control=Y
|qualityscore_familial=0
|qualityscore_severity=3
|qualitycomment_severity=Y
|qualityscore_treatability=2
|qualitycomment_treatability=Y
|in_omim=Y
|pph2_score=0.006
|nblosum100=4
|autoscore=2
|webscore=N
|variant_evidence=0
|clinical_importance=2
|summary_short=This variant is associated with inosine triphosphate pyrophosphohydrolase deficiency and may be associated with an adverse reaction to thiopurine drugs (which are used as immunosuppressants). Homozygotes have no detectable ITPase activity, individuals compound heterozygous with another less severe mutation also have severely reduced enzyme activity.
}}

{{PMID Auto
|PMID=23139603
|Title=Several factors including ITPA polymorphism influence ribavirin-induced anemia in chronic hepatitis C
|OA=1
}}

[[Hepatitis C Treatment Side Effects]]

{{PMID Auto
|PMID=23195617
|Title=Impact of genetic SLC28 transporter and ITPA variants on ribavirin serum level, hemoglobin drop and therapeutic response in patients with HCV infection
}}

{{PMID Auto
|PMID=23538996
|Title=Pre-treatment role of inosine triphosphate pyrophosphatase polymorphism for predicting anemia in Egyptian hepatitis C virus patients
|OA=1
}}

{{PMID Auto GWAS
  |PMID=20173735
  |Trait=Chronic Hepatitis C infection
  |Title=ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C.
  |RiskAllele=A
  |Pval=2E-58
  |OR=NR
  |ORtxt=NR
  }}

{{PMID Auto
|PMID=23933495
|Title=Association of ITPA polymorphisms rs6051702/rs1127354 instead of rs7270101/rs1127354 as predictor of ribavirin-associated anemia in chronic hepatitis C treated patients
}}

{{PMID Auto
|PMID=24621321
|Title=Severe thrombocytopenia in a patient with inosine triphosphatase (ITPA)-CC genotype caused by pegylated interferon (IFN)-alpha-2a with ribavirin therapy: a case report
|OA=1
}}

{{PMID Auto
|PMID=22584257
|Title=Genetic variants at the ITPA locus protect against ribavirin-induced hemolytic anemia and dose reduction in an HCV G2/G3 cohort.
}}

{{PMID Auto
|PMID=22585729
|Title=ITPA gene polymorphisms significantly affect hemoglobin decline and treatment outcomes in patients coinfected with HIV and HCV.
|OA=1
}}

{{PMID Auto
|PMID=23133602
|Title=Pharmacogenetics of efficacy and safety of HCV treatment in HCV-HIV coinfected patients: significant associations with IL28B and SOCS3 gene variants.
|OA=1
}}

{{PMID Auto
|PMID=23201294
|Title=Allelic inhibition of displacement activity: a simplified one tube allele-specific PCR for evaluation of ITPA polymorphisms.
}}

{{PMID Auto
|PMID=23297176
|Title=Model incorporating the ITPA genotype identifies patients at high risk of anemia and treatment failure with pegylated-interferon plus ribavirin therapy for chronic hepatitis C.
}}

{{PMID Auto
|PMID=23490380
|Title=An automated rapid detection system using the quenching probe method for detecting interleukin 28B and inosine triphosphatase single nucleotide polymorphisms in chronic hepatitis C.
}}

{{PMID Auto
|PMID=23730840
|Title=Role of IL28B and inosine triphosphatase polymorphisms in the treatment of chronic hepatitis C virus genotype 6 infection.
}}

{{PMID Auto
|PMID=24750345
|Title=ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients infected with HCV genotype 1 and favourable IL28B type
}}

{{PMID Auto
|PMID=23707372
|Title=Clinical milestones for the prediction of severe anemia by chronic hepatitis C patients receiving telaprevir-based triple therapy
}}

{{PMID Auto
|PMID=24304455
|Title=Inosine triphosphatase deficiency helps predict anaemia, anaemia management and response in chronic hepatitis C therapy
}}

{{PMID Auto
|PMID=23980585
|Title=Relationship between inosine triphosphate genotype and outcome of extended therapy in hepatitis C virus patients with a late viral response to pegylated-interferon and ribavirin
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}