PPA2 (inorganic pyrophosphatase 2)

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Gene SNPs miRNA Gene ontology Other IDs Protein Pathways Associated diseases Related genes Diseases linked via similar genes

Gene

• Entrez ID: 27068
• Gene name: Inorganic pyrophosphatase 2
• Gene symbol: PPA2
• Synonyms (NCBI Gene): HSPC124, SCFAI, SCFI, SID6-306
• Chromosome: 4
• Chromosome location: 4q24
• 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 hydrol

SNPs Show/Hide all (9)

SNP ID	Visualize variation	Clinical significance	Consequence
rs138215926	G>A	Pathogenic	Missense variant, coding sequence variant
rs139076647	C>A,T	Likely-pathogenic	Missense variant, coding sequence variant, intron variant
rs146013446	C>T	Likely-pathogenic, pathogenic	Missense variant, intron variant, coding sequence variant
rs151331559	G>A,C,T	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant, stop gained
rs546693824	G>A	Pathogenic	Missense variant, intron variant, coding sequence variant
rs772083375	G>A,C	Likely-pathogenic	Coding sequence variant, intron variant, missense variant
rs1057517678	T>G	Pathogenic	Coding sequence variant, missense variant
rs1057517679	T>C	Pathogenic	Coding sequence variant, missense variant, intron variant
rs1057517680	C>A	Pathogenic	Coding sequence variant, missense variant, intron variant

miRNA Show/Hide all (112)

miRTarBase ID	miRNA	Experiments	Reference
MIRT016388	hsa-miR-193b-3p	Proteomics	21512034
MIRT023639	hsa-miR-1-3p	Proteomics	18668040
MIRT1251165	hsa-miR-4677-3p	CLIP-seq
MIRT1251166	hsa-miR-4679	CLIP-seq
MIRT1251167	hsa-miR-3074-3p	CLIP-seq
MIRT2074102	hsa-miR-122	CLIP-seq
MIRT2074103	hsa-miR-1224-3p	CLIP-seq
MIRT2074104	hsa-miR-1913	CLIP-seq
MIRT2074105	hsa-miR-193a-3p	CLIP-seq
MIRT2074106	hsa-miR-193b	CLIP-seq
MIRT2074107	hsa-miR-216b	CLIP-seq
MIRT2074108	hsa-miR-3135	CLIP-seq
MIRT2074109	hsa-miR-3135b	CLIP-seq
MIRT2074110	hsa-miR-324-3p	CLIP-seq
MIRT2074111	hsa-miR-3545-3p	CLIP-seq
MIRT2074112	hsa-miR-3652	CLIP-seq
MIRT2074113	hsa-miR-3663-5p	CLIP-seq
MIRT2074114	hsa-miR-3929	CLIP-seq
MIRT2074115	hsa-miR-4419b	CLIP-seq
MIRT2074116	hsa-miR-4430	CLIP-seq
MIRT2074117	hsa-miR-4435	CLIP-seq
MIRT2074118	hsa-miR-4478	CLIP-seq
MIRT2074119	hsa-miR-4635	CLIP-seq
MIRT2074120	hsa-miR-4680-5p	CLIP-seq
MIRT2074121	hsa-miR-4755-3p	CLIP-seq
MIRT2074122	hsa-miR-645	CLIP-seq
MIRT2074123	hsa-miR-892b	CLIP-seq
MIRT2074102	hsa-miR-122	CLIP-seq
MIRT2074103	hsa-miR-1224-3p	CLIP-seq
MIRT2074104	hsa-miR-1913	CLIP-seq
MIRT2074107	hsa-miR-216b	CLIP-seq
MIRT2074108	hsa-miR-3135	CLIP-seq
MIRT2074109	hsa-miR-3135b	CLIP-seq
MIRT2074110	hsa-miR-324-3p	CLIP-seq
MIRT2074111	hsa-miR-3545-3p	CLIP-seq
MIRT2301123	hsa-miR-3614-5p	CLIP-seq
MIRT2074112	hsa-miR-3652	CLIP-seq
MIRT2074114	hsa-miR-3929	CLIP-seq
MIRT2301124	hsa-miR-4294	CLIP-seq
MIRT2074115	hsa-miR-4419b	CLIP-seq
MIRT2074116	hsa-miR-4430	CLIP-seq
MIRT2074118	hsa-miR-4478	CLIP-seq
MIRT2301125	hsa-miR-4670-3p	CLIP-seq
MIRT2074120	hsa-miR-4680-5p	CLIP-seq
MIRT2074122	hsa-miR-645	CLIP-seq
MIRT2301126	hsa-miR-890	CLIP-seq
MIRT2456968	hsa-miR-1273f	CLIP-seq
MIRT2456969	hsa-miR-3149	CLIP-seq
MIRT2456970	hsa-miR-3170	CLIP-seq
MIRT2456971	hsa-miR-3976	CLIP-seq
MIRT2456972	hsa-miR-4735-5p	CLIP-seq
MIRT2456973	hsa-miR-4775	CLIP-seq
MIRT2456974	hsa-miR-4794	CLIP-seq
MIRT2456975	hsa-miR-590-3p	CLIP-seq
MIRT2456976	hsa-miR-633	CLIP-seq
MIRT2074103	hsa-miR-1224-3p	CLIP-seq
MIRT2597684	hsa-miR-1234	CLIP-seq
MIRT2456968	hsa-miR-1273f	CLIP-seq
MIRT2597685	hsa-miR-1343	CLIP-seq
MIRT2597686	hsa-miR-139-5p	CLIP-seq
MIRT2074104	hsa-miR-1913	CLIP-seq
MIRT2597687	hsa-miR-193a-5p	CLIP-seq
MIRT2456969	hsa-miR-3149	CLIP-seq
MIRT2456970	hsa-miR-3170	CLIP-seq
MIRT2074110	hsa-miR-324-3p	CLIP-seq
MIRT2597688	hsa-miR-3618	CLIP-seq
MIRT2597689	hsa-miR-378g	CLIP-seq
MIRT2456971	hsa-miR-3976	CLIP-seq
MIRT2597690	hsa-miR-4277	CLIP-seq
MIRT2597691	hsa-miR-4437	CLIP-seq
MIRT2597692	hsa-miR-4438	CLIP-seq
MIRT2597693	hsa-miR-4659a-3p	CLIP-seq
MIRT2597694	hsa-miR-4659b-3p	CLIP-seq
MIRT2597695	hsa-miR-4674	CLIP-seq
MIRT2456972	hsa-miR-4735-5p	CLIP-seq
MIRT2456973	hsa-miR-4775	CLIP-seq
MIRT2456974	hsa-miR-4794	CLIP-seq
MIRT2597696	hsa-miR-501-3p	CLIP-seq
MIRT2597697	hsa-miR-502-3p	CLIP-seq
MIRT2597698	hsa-miR-5095	CLIP-seq
MIRT2456975	hsa-miR-590-3p	CLIP-seq
MIRT2456976	hsa-miR-633	CLIP-seq
MIRT2597699	hsa-miR-767-5p	CLIP-seq
MIRT2074102	hsa-miR-122	CLIP-seq
MIRT2456968	hsa-miR-1273f	CLIP-seq
MIRT2597685	hsa-miR-1343	CLIP-seq
MIRT2074108	hsa-miR-3135	CLIP-seq
MIRT2074109	hsa-miR-3135b	CLIP-seq
MIRT2456969	hsa-miR-3149	CLIP-seq
MIRT2456970	hsa-miR-3170	CLIP-seq
MIRT2688382	hsa-miR-3182	CLIP-seq
MIRT2074112	hsa-miR-3652	CLIP-seq
MIRT2597689	hsa-miR-378g	CLIP-seq
MIRT2074114	hsa-miR-3929	CLIP-seq
MIRT2456971	hsa-miR-3976	CLIP-seq
MIRT2597690	hsa-miR-4277	CLIP-seq
MIRT2074115	hsa-miR-4419b	CLIP-seq
MIRT2074116	hsa-miR-4430	CLIP-seq
MIRT2597691	hsa-miR-4437	CLIP-seq
MIRT2074118	hsa-miR-4478	CLIP-seq
MIRT2597693	hsa-miR-4659a-3p	CLIP-seq
MIRT2597694	hsa-miR-4659b-3p	CLIP-seq
MIRT2597695	hsa-miR-4674	CLIP-seq
MIRT2456972	hsa-miR-4735-5p	CLIP-seq
MIRT2456973	hsa-miR-4775	CLIP-seq
MIRT2456974	hsa-miR-4794	CLIP-seq
MIRT2597696	hsa-miR-501-3p	CLIP-seq
MIRT2597697	hsa-miR-502-3p	CLIP-seq
MIRT2456975	hsa-miR-590-3p	CLIP-seq
MIRT2456976	hsa-miR-633	CLIP-seq
MIRT2074122	hsa-miR-645	CLIP-seq
MIRT2597699	hsa-miR-767-5p	CLIP-seq

Gene ontology (GO) Show/Hide all (19)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000287	Function	Magnesium ion binding	IEA
GO:0004427	Function	Inorganic diphosphate phosphatase activity	IBA
GO:0004427	Function	Inorganic diphosphate phosphatase activity	IDA	27523597
GO:0004427	Function	Inorganic diphosphate phosphatase activity	IEA
GO:0004722	Function	Protein serine/threonine phosphatase activity	IEA
GO:0005515	Function	Protein binding	IPI	32814053
GO:0005737	Component	Cytoplasm	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	27523597
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006796	Process	Phosphate-containing compound metabolic process	IBA
GO:0006796	Process	Phosphate-containing compound metabolic process	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0045202	Component	Synapse	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0051881	Process	Regulation of mitochondrial membrane potential	IMP	27523598
GO:0071344	Process	Diphosphate metabolic process	IMP	27523597

Other IDs

• MIM: 609988
• HGNC: 28883
• e!Ensembl: ENSG00000138777

Protein

• UniProt ID: Q9H2U2
• Protein name: Inorganic pyrophosphatase 2, mitochondrial (EC 3.6.1.1) (Pyrophosphatase SID6-306) (Pyrophosphate phospho-hydrolase 2) (PPase 2)
• Protein function: Hydrolyzes inorganic pyrophosphate (PubMed:27523597). This activity is essential for correct regulation of mitochondrial membrane potential, and mitochondrial organization and function (PubMed:27523598). {ECO:0000269|PubMed:27523597, ECO:0000269
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00719	Pyrophosphatase	94 → 276	Inorganic pyrophosphatase	Domain

• Tissue specificity: TISSUE SPECIFICITY: Detected in brain, gastric carcinoma, lung, ovary, skeletal muscle, umbilical cord blood and a cell line derived from kidney proximal tubule epithelium. {ECO:0000269|PubMed:15210126}.
• Sequence:

  MSALLRLLRTGAPAAACLRLGTSAGTGSRRAMALYHTEERGQPCSQNYRLFFKNVTGHYI
  SPFHDIPLKVNSKEENGIPMKKARNDEYENLFNMIVEIPRWTNAKMEIATKEPMNPIKQY
  VKDGKLRYVANIFPYKGYIWNYGTLPQTWEDPHEKDKSTNCFGDNDPIDVCEIGSKILSC
  GEVIHVKILGILALIDEGETDWKLIAINANDPEASKFHDIDDVKKFKPGYLEATLNWFRL
  YKVPDGKPENQFAFNGEFKNKAFALEVIKSTHQCWKALLMKKCNGGAINCTNVQISDSPF
  RCTQEEARSLVESVSSSPNKESNEEEQVWHFLGK

• Sequence length: 334

Pathways

KEGG Pathway	Reactome Pathway
Oxidative phosphorylation	Mitochondrial tRNA aminoacylation
	Pyrophosphate hydrolysis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Cardiovascular phenotype	Likely pathogenic; Pathogenic	rs146013446, rs371147281	RCV005404543 RCV005404223	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Sudden cardiac failure, alcohol-induced	Likely pathogenic; Pathogenic	rs1723387280, rs752062224, rs146013446, rs139076647, rs138215926	RCV001638074 RCV001638070 RCV000412531 RCV005033928 RCV000412589	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Sudden cardiac failure, infantile	Likely pathogenic; Pathogenic	rs1723387280, rs752062224, rs772083375, rs1057517678, rs146013446, rs1057517679, rs1057517680, rs139076647, rs138215926, rs546693824, rs1187924642	RCV001638073 RCV001638069 RCV000412514 RCV000412573 RCV000412629 RCV000412577 RCV000412661 RCV000412508 RCV002272221 RCV000412653 RCV001095794	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations Show/Hide Unknown Diseases (15)
Phenotype Name	Clinical Significance	Source	Reference	Evidence Score
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	35764056	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	GWAS catalog	35764056	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	29059683	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	29059683	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DILATED CARDIOMYOPATHY	—	CTD, ClinGen	16300924, 27523597, 27523598, 30384889, 31705601, 33028643, 33826954, 34400813, 37249496, 37269378, 37869221, 38582264	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Likely benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	35835914	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IRRITABLE BOWEL SYNDROME	—	GWAS catalog	38102678	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
mitochondrial cardiomyopathy and sudden cardiac failure	Uncertain significance	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Uncertain significance; Benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PPA2-related disorder	Conflicting classifications of pathogenicity; Benign; Likely benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign	ClinVar	—	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining Show/Hide Text Mining Associations (17)
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma	Adenocarcinoma	BEFREE	28062797		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	GWASCAT_DG	29059683		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Neoplasms	Breast neoplasm	Pubtator	26354892, 39176095	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	BEFREE	27523597, 31705601		★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	Pubtator	31705601, 34400813, 38582264	Associate	★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart disease	Pubtator	34400813	Associate	★☆☆☆☆ Found in Text Mining only
Heart Failure	Heart failure	Pubtator	34400813	Associate	★☆☆☆☆ Found in Text Mining only
Hypertension	Hypertension	Pubtator	33028643	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial Diseases	BEFREE	27523597, 27523598		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	27523598, 38582264	Associate	★☆☆☆☆ Found in Text Mining only
Myocarditis	Myocarditis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	Pubtator	38014648	Associate	★☆☆☆☆ Found in Text Mining only
SUDDEN CARDIAC FAILURE, INFANTILE	SUDDEN CARDIAC FAILURE	GENOMICS_ENGLAND_DG	27523597, 27523598		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
SUDDEN CARDIAC FAILURE, INFANTILE	SUDDEN CARDIAC FAILURE	UNIPROT_DG	27523597, 27523598		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
SUDDEN CARDIAC FAILURE, INFANTILE	SUDDEN CARDIAC FAILURE	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
SUDDEN CARDIAC FAILURE, INFANTILE	SUDDEN CARDIAC FAILURE	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Related Genes

Sort by: Blended Diseases Pathways Evidence source

HSPA4 2 shared diseasesDilated cardiomyopathy, Irritable bowel syndrome 1 shared evidence sourceGWAS catalog (Irritable bowel syndrome) Related via 2 shared diseases including Dilated cardiomyopathy, Irritable bowel syndrome — evidence mostly GWAS catalog. WDR12 2 shared diseasesDilated cardiomyopathy, Irritable bowel syndrome 2 shared evidence sourcesCTD (Dilated cardiomyopathy), GWAS catalog (Irritable bowel syndrome) Related via 2 shared diseases including Dilated cardiomyopathy, Irritable bowel syndrome — evidence mostly CTD. PPA1 2 shared pathwaysOxidative phosphorylation, Pyrophosphate hydrolysis Related via 2 shared pathways including Oxidative phosphorylation, Pyrophosphate hydrolysis. LMOD2 1 shared diseaseDilated cardiomyopathy 2 shared evidence sourcesCTD (Dilated cardiomyopathy), ClinGen (Dilated cardiomyopathy) Related via 1 shared disease including Dilated cardiomyopathy — evidence mostly CTD. GATAD1 1 shared diseaseDilated cardiomyopathy 2 shared evidence sourcesCTD (Dilated cardiomyopathy), ClinGen (Dilated cardiomyopathy) Related via 1 shared disease including Dilated cardiomyopathy — evidence mostly CTD.

Related Gene	Shared Diseases	Shared Disease Names	Shared Pathways	Shared Pathway Names	Shared Evidence Sources	Shared Evidence Names
HSPA4	2	["Dilated cardiomyopathy","Irritable bowel syndrome"]	0	[]	1	["GWAS catalog (Irritable bowel syndrome)"]
WDR12	2	["Dilated cardiomyopathy","Irritable bowel syndrome"]	0	[]	2	["CTD (Dilated cardiomyopathy)","GWAS catalog (Irritable bowel syndrome)"]
PPA1	0	[]	2	["Oxidative phosphorylation","Pyrophosphate hydrolysis"]	0	[]
LMOD2	1	["Dilated cardiomyopathy"]	0	[]	2	["CTD (Dilated cardiomyopathy)","ClinGen (Dilated cardiomyopathy)"]
GATAD1	1	["Dilated cardiomyopathy"]	0	[]	2	["CTD (Dilated cardiomyopathy)","ClinGen (Dilated cardiomyopathy)"]

Diseases Linked via Similar Genes

Androgenetic alopecia Linked via 1 of 5 related genesHSPA4 Bipolar disorder Linked via 1 of 5 related genesHSPA4 Cardiovascular disease Linked via 1 of 5 related genesHSPA4 Obstructive pulmonary disease Linked via 1 of 5 related genesHSPA4 Colorectal cancer Linked via 1 of 5 related genesHSPA4

Disease	Linked Via (Gene Count)	Linked Via (Gene Names)
Androgenetic alopecia	1	["HSPA4"]
Bipolar disorder	1	["HSPA4"]
Cardiovascular disease	1	["HSPA4"]
Obstructive pulmonary disease	1	["HSPA4"]
Colorectal cancer	1	["HSPA4"]