PPA2 Gene - Inorganic Pyrophosphatase 2
Mitochondrial pyrophosphatase essential for energy metabolism and linked to sudden cardiac death
Gene Information Card
| Symbol | PPA2 |
|---|---|
| Full Name | Inorganic pyrophosphatase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q24 |
| NCBI Gene ID | 27068 ncbi.nlm.nih.gov/gene/27068 |
| Ensembl ID | ENSG00000138684 |
| UniProt ID | Q9H2U2 |
| OMIM ID | 609988 |
| HGNC ID | 28883 |
| Aliases | PPA2, PPase2, pyrophosphatase (inorganic) 2 |
Description
The PPA2 gene encodes the mitochondrial inorganic pyrophosphatase 2, an enzyme that catalyzes the hydrolysis of inorganic pyrophosphate (PPi) to two phosphate ions. This reaction is critical for mitochondrial energy metabolism, as it drives biosynthetic reactions and maintains cellular phosphate homeostasis. Mutations in PPA2 are associated with early-onset sudden cardiac death and cardiomyopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Sudden cardiac death (infantile/childhood) | Loss-of-function mutations impair mitochondrial pyrophosphate hydrolysis, leading to energy deficiency and cardiac arrhythmia | ClinVar, OMIM |
| Cardiomyopathy, dilated | Defective mitochondrial function due to PPA2 deficiency disrupts ATP production in cardiac muscle | ClinVar, OMIM |
| Mitochondrial disease | Generalized mitochondrial dysfunction from impaired PPi metabolism affects multiple tissues | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Kidney | 7.1 | Medium |
| Skeletal muscle | 6.9 | Medium |
| Brain | 4.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.2 | High expression |
| HeLa | 8.5 | Medium expression |
| K562 | 6.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.514C>T (p.Arg172Trp) | Missense | Rare | Loss of function; associated with sudden cardiac death |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of protein; severe phenotype |
| c.680G>A (p.Arg227His) | Missense | Rare | Reduced enzyme activity; cardiomyopathy |
Mutation functional classification
Loss of Function (LOF)
Most PPA2 mutations are loss-of-function, reducing or abolishing pyrophosphatase activity, leading to mitochondrial dysfunction.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with dimerization or substrate binding.
View complete mutation data：
Gene Ontology (GO)
| • inorganic diphosphatase activity (GO:0004427) | • mitochondrion (GO:0005739) |
| • phosphate-containing compound metabolic process (GO:0006796) | • hydrolase activity (GO:0016787) |
Pathways
• Mitochondrial pyrophosphate metabolism
• Oxidative phosphorylation (indirect)
Protein Summary
PPA2 is a mitochondrial enzyme that hydrolyzes inorganic pyrophosphate to phosphate, a reaction essential for driving biosynthetic reactions and maintaining energy balance. It forms a homodimer and is highly expressed in tissues with high energy demand, such as heart and muscle. Loss-of-function mutations cause severe cardiac phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PPA2 Knockout HEK293 Cell Line | EDJ-KQ8663 | Human | 27068 | Details Get a Quote |
| PAPPA2 Knockout HEK293 Cell Line | EDJ-KQ13887 | Human | 60676 | Details Get a Quote |
| PPA2 Knockout HCT 116 Cell Line | EDJ-KQ34837 | Human | 27068 | Details Get a Quote |
| PPA2 Knockout HeLa Cell Line | EDJ-KQ34838 | Human | 27068 | Details Get a Quote |
| DPPA2 Knockout HEK293 Cell Line | EDJ-KQ52057 | Human | 151871 | Details Get a Quote |
| PAPPA2 Knockout HeLa Cell Line | EDJ-KQ56986 | Human | 60676 | Details Get a Quote |
| DPPA2 Knockout HeLa Cell Line | EDJ-KQ58696 | Human | 151871 | Details Get a Quote |
| PPA2 Knockout A-549 Cell Line | EDJ-KQ64478 | Human | 27068 | Details Get a Quote |
| PAPPA2 Knockout A-549 Cell Line | EDJ-KQ65489 | Human | 60676 | Details Get a Quote |
| DPPA2 Knockout A-549 Cell Line | EDJ-KQ67180 | Human | 151871 | Details Get a Quote |
| PAPPA2 Knockout HCT 116 Cell Line | EDJ-KQ73927 | Human | 60676 | Details Get a Quote |
| DPPA2 Knockout HCT 116 Cell Line | EDJ-KQ75582 | Human | 151871 | Details Get a Quote |
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