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    PPA2 inorganic pyrophosphatase 2 [ Homo sapiens (human) ]

    Gene ID: 27068, updated on 27-Nov-2024

    Summary

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    Official Symbol
    PPA2provided by HGNC
    Official Full Name
    inorganic pyrophosphatase 2provided by HGNC
    Primary source
    HGNC:HGNC:28883
    See related
    Ensembl:ENSG00000138777 MIM:609988; AllianceGenome:HGNC:28883
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SCFI; SCFAI; HSPC124; SID6-306
    Summary
    The protein encoded by this gene is localized to the mitochondrion, is highly similar to members of the inorganic pyrophosphatase (PPase) family, and contains the signature sequence essential for the catalytic activity of PPase. PPases catalyze the hydrolysis of pyrophosphate to inorganic phosphate, which is important for the phosphate metabolism of cells. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in kidney (RPKM 25.8), colon (RPKM 25.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PPA2 in Genome Data Viewer
    Location:
    4q24
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (105369077..105474070, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (108679986..108784941, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (106290234..106395227, complement)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124900868 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15606 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21777 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21778 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15607 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:106083203-106083911 Neighboring gene tet methylcytosine dioxygenase 2 Neighboring gene TET2 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21779 Neighboring gene RNA, 7SL, cytoplasmic 89, pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr4:106307176-106307329 Neighboring gene RNA, U6 small nuclear 553, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21780 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21781 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15608 Neighboring gene eukaryotic translation elongation factor 1 alpha 1 pseudogene 9 Neighboring gene PIMREG pseudogene 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Sudden unexpected death in asymptomatic infants due to PPA2 variants. Phoon CKL, et al. Mol Genet Genomic Med, 2020 Jan. PMID 31705601, Free PMC Article
    2. Structural and biochemical characterization of inorganic pyrophosphatase from Homo sapiens. Hu F, et al. Biochem Biophys Res Commun, 2020 Dec 17. PMID 33036755
    3. PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families. Guimier A, et al. Genet Med, 2021 Dec. PMID 34400813, Free PMC Article
    4. Ocadaic acid retains caveolae in multicaveolar clusters. Kiss AL, et al. Pathol Oncol Res, 2009 Sep. PMID 19067239
    5. Hypothetical proteins with putative enzyme activity in human amnion, lymphocyte, bronchial epithelial and kidney cell lines. Afjehi-Sadat L, et al. Biochim Biophys Acta, 2004 Jul 1. PMID 15210126

    See all (80) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families.
      Title: PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families.
    2. Sudden unexpected death in asymptomatic infants due to PPA2 variants.
      Title: Sudden unexpected death in asymptomatic infants due to PPA2 variants.
    3. Structural and biochemical characterization of inorganic pyrophosphatase from Homo sapiens.
      Title: Structural and biochemical characterization of inorganic pyrophosphatase from Homo sapiens.
    4. data demonstrate that PPA2 is an essential gene in yeast and that biallelic mutations in PPA2 cause a mitochondrial disease leading to sudden cardiac arrest in infants
      Title: Biallelic PPA2 Mutations Cause Sudden Unexpected Cardiac Arrest in Infancy.
    5. findings confirm the pathogenicity of PPA2 mutations and suggest that PPA2 is a cardiomyopathy-associated protein, which has a greater physiological importance in mitochondrial function than previously recognized
      Title: Sudden Cardiac Death Due to Deficiency of the Mitochondrial Inorganic Pyrophosphatase PPA2.
    6. Single nucleotide polymorphisms in PPA2 is associated with response to antipsychotic agents in schizophrenia.
      Title: Genome-wide association study of patient-rated and clinician-rated global impression of severity during antipsychotic treatment.
    7. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    8. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    9. We think that PP2A can be one of the key components to regulate the fusion of various endocytotic compartments and /or the trafficking along the microtubules.
      Title: Ocadaic acid retains caveolae in multicaveolar clusters.
    10. No pathogenic mutations were identified in the PPA2 gene in patients with mitochondrial DNA depletion syndromes (MDS).
      Title: Human mitochondrial pyrophosphatase: cDNA cloning and analysis of the gene in patients with mtDNA depletion syndromes.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Sudden cardiac failure, alcohol-induced
    MedGen: C4310663 OMIM: 617223 GeneReviews: Not available
    		Compare labs
    Sudden cardiac failure, infantile
    MedGen: C4310664 OMIM: 617222 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide association study of host genetic determinants of the antibody response to Anthrax Vaccine Adsorbed.
    EBI GWAS Catalog
    Genome-wide association study of patient-rated and clinician-rated global impression of severity during antipsychotic treatment.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ20459, MGC49850

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables inorganic diphosphate phosphatase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables inorganic diphosphate phosphatase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables magnesium ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein serine/threonine phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in diphosphate metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in phosphate-containing compound metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of mitochondrial membrane potential IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in synapse IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    inorganic pyrophosphatase 2, mitochondrial
    Names
    PPase 2
    pyrophosphatase (inorganic) 2
    pyrophosphatase SID6-306
    pyrophosphate phospho-hydrolase 2
    NP_008834.3
    NP_789842.2
    NP_789843.2
    NP_789845.1

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_053007.1 RefSeqGene

      Range
      5009..109994
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_006903.4 → NP_008834.3  inorganic pyrophosphatase 2, mitochondrial isoform 2 precursor

      See identical proteins and their annotated locations for NP_008834.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame coding segment, when compared to variant 1. The resulting isoform (2) is shorter and lacks an internal region, as compared to isoform 1.
      Source sequence(s)
      AI419577, AK000466, BC035569, BC057219, CN423093
      Consensus CDS
      CCDS3668.2
      UniProtKB/TrEMBL
      A8K0P2
      Related
      ENSP00000313061.8, ENST00000348706.9
      Conserved Domains (1) summary
      cl00217
      Location:4 → 257
      pyrophosphatase; Inorganic pyrophosphatase. These enzymes hydrolyze inorganic pyrophosphate (PPi) to two molecules of orthophosphates (Pi). The reaction requires bivalent cations. The enzymes in general exist as homooligomers.

    2. NM_176866.2 → NP_789842.2  inorganic pyrophosphatase 2, mitochondrial isoform 3 precursor

      See identical proteins and their annotated locations for NP_789842.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an in-frame coding segment, when compared to variant 1. The resulting isoform (3) is shorter and lacks an internal region, as compared to isoform 1.
      Source sequence(s)
      AI419577, AK000466, BC039462, BM848099, CN423093
      Consensus CDS
      CCDS3669.2
      UniProtKB/Swiss-Prot
      Q9H2U2
      Related
      ENSP00000389957.2, ENST00000432483.6
      Conserved Domains (1) summary
      cl00217
      Location:4 → 184
      pyrophosphatase; Inorganic pyrophosphatase. These enzymes hydrolyze inorganic pyrophosphate (PPi) to two molecules of orthophosphates (Pi). The reaction requires bivalent cations. The enzymes in general exist as homooligomers.

    3. NM_176867.3 → NP_789843.2  inorganic pyrophosphatase 2, mitochondrial isoform 4 precursor

      See identical proteins and their annotated locations for NP_789843.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an in-frame coding segment, when compared to variant 1. The resulting isoform (4) is shorter and lacks an internal region, as compared to isoform 1.
      Source sequence(s)
      AI419577, AK000466, BC022803, BC039462, CN423093
      Consensus CDS
      CCDS34043.1
      UniProtKB/Swiss-Prot
      Q9H2U2
      Related
      ENSP00000340352.3, ENST00000354147.7
      Conserved Domains (1) summary
      cl00217
      Location:53 → 120
      pyrophosphatase; Inorganic pyrophosphatase. These enzymes hydrolyze inorganic pyrophosphate (PPi) to two molecules of orthophosphates (Pi). The reaction requires bivalent cations. The enzymes in general exist as homooligomers.

    4. NM_176869.3 → NP_789845.1  inorganic pyrophosphatase 2, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_789845.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript, and encodes the longest isoform (1).
      Source sequence(s)
      AF217187, AI419577, AK000466, BC035569
      Consensus CDS
      CCDS3667.1
      UniProtKB/Swiss-Prot
      B4DLP7, F8WDN9, I6L9B6, Q4W5E9, Q6PG51, Q8TBW0, Q96E55, Q9H0T0, Q9H2U2, Q9NX37, Q9P033, Q9ULX0
      UniProtKB/TrEMBL
      A8K0P2
      Related
      ENSP00000343885.5, ENST00000341695.10
      Conserved Domains (1) summary
      cl00217
      Location:4 → 286
      pyrophosphatase; Inorganic pyrophosphatase. These enzymes hydrolyze inorganic pyrophosphate (PPi) to two molecules of orthophosphates (Pi). The reaction requires bivalent cations. The enzymes in general exist as homooligomers.

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      105369077..105474070 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      108679986..108784941 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_001034191.1: Suppressed sequence

      Description
      NM_001034191.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.

    2. NM_001034192.1: Suppressed sequence

      Description
      NM_001034192.1: This RefSeq was permanently suppressed because currently there is support for the transcript but not for the protein.

    3. NM_001034193.1: Suppressed sequence

      Description
      NM_001034193.1: This RefSeq was permanently suppressed because currently there is support for the transcript but not for the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9H2U2.2 GenPept UniProtKB/Swiss-Prot:Q9H2U2

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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