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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
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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

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