ITPA

Protein identityUniProt · HPA

UniProt accession

Q9BY32

Gene

ITPA

Ensembl

ENSG00000125877

Chromosome

20

Canonical length

194 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Cytosol

Quaternary structure

Homodimer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

194 residues, UniProt reviewed canonical sequence.

>Q9BY32|ITPA
     1  MAASLVGKKI VFVTGNAKKL EEVVQILGDK FPCTLVAQKI DLPEYQGEPD EISIQKCQEA
    61  VRQVQGPVLV EDTCLCFNAL GGLPGPYIKW FLEKLKPEGL HQLLAGFEDK SAYALCTFAL
   121  STGDPSQPVR LFRGRTSGRI VAPRGCQDFG WDPCFQPDGY EQTYAEMPKA EKNAVSHRFR
   181  ALLELQEYFG SLAA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ITPA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

51 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ITPA.

Disease | AllUniProt

Conditions ITPA is implicated in, by any mechanism.

• Inosine triphosphate pyrophosphohydrolase deficiency (ITPAD) MIM:613850
• Developmental and epileptic encephalopathy 35 (DEE35) MIM:616647

Disease | GeneticClinVar

40 pathogenic / likely-pathogenic of 340 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Inosine triphosphatase deficiency
• Developmental and epileptic encephalopathy, 35
• Infantile epileptic dyskinetic encephalopathy
• Hypodontia
• ITPA-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.35

gnomAD pLI

0

gnomAD missense Z

0.12

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 9% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• chromosome organization
• nucleoside triphosphate catabolic process
• deoxyribonucleoside triphosphate catabolic process
• ITP catabolic process

Molecular functions

• dITP diphosphatase activity
• identical protein binding
• metal ion binding
• nucleoside triphosphate diphosphatase activity
• nucleotide binding
• ITP diphosphatase activity
• XTP diphosphatase activity

Cellular components

• cytoplasm
• cytosol
• nucleoplasm

Protein domainsUniProt · Pfam · InterPro

• Inosine triphosphate pyrophosphatase-like
• RdgB/HAM1
• Inosine triphosphate pyrophosphatase
• Ham1 family

KeywordsUniProt

• Acetylation
• Cytoplasm
• Epilepsy
• Hydrolase
• Magnesium
• Metal-binding
• Nucleotide metabolism
• Nucleotide-binding