HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PPA1
inorganic pyrophosphatase 1
Chromosome 10 · 10q22.1
NCBI Gene: 5464Ensembl: ENSG00000180817.13HGNC: HGNC:9226UniProt: Q15181
154PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular exosomeinorganic diphosphate phosphatase activityphosphate-containing compound metabolic processMAP kinase serine/threonine phosphatase activityneurodegenerative diseaseneuroinflammatory disorderneoplasmbreast cancer
✦AI Summary

PPA1 (inorganic pyrophosphatase 1) is a metabolic enzyme that catalyzes pyrophosphate hydrolysis, playing critical roles across multiple physiological systems. In adipose tissue, PPA1 promotes adipogenesis by stabilizing C/EBPβ and C/EBPδ proteins in a catalytic-activity-independent manner 1, and facilitates adipocyte browning through regulation of mitochondrial biogenesis as a target gene of NRF1 2. PPA1 deficiency causes lipodystrophy, hepatic steatosis, and insulin resistance, while overexpression restores adipogenesis in diabetic models. In the nervous system, cell-penetrating TAT-PPA1 protects dopaminergic neurons against oxidative stress and MPTP-induced damage by suppressing MAPK signaling and ROS production, suggesting potential for Parkinson's disease treatment 3. Conversely, PPA1 is significantly upregulated in multiple cancers—particularly lung, ovarian, gastric, and pancreatic cancers—where high expression correlates with advanced stages, poor prognosis, and metastasis 456. In cancer cells, PPA1 promotes proliferation through Wnt/β-catenin and TP53/p21 pathways; its suppression increases apoptosis. PPA1 was identified as a therapeutic target for diabetic microangiopathy through genome-wide Mendelian randomization analysis 7. Recent molecular docking studies identified devazepide and quinotolast as potential PPA1 inhibitors for cancer repurposing 8. These findings position PPA1 as a dual-function protein: beneficial in metabolic and neurodegenerative contexts, but oncogenic in cancer.

Sources cited
1
PPA1 promotes adipogenesis by stabilizing C/EBPβ and C/EBPδ proteins independently of catalytic activity; PPA1 deficiency causes lipodystrophy, hepatic steatosis, and insulin resistance
PMID: 38762596
2
PPA1 is critical for adipocyte browning and mitochondrial function; acts as target gene of NRF1; PPA1+/- mice show reduced browning capacity and cold intolerance
PMID: 37549601
3
TAT-PPA1 protects dopaminergic neurons against MPTP-induced oxidative stress through MAPK pathway suppression; prevents ROS production and motor dysfunction in PD models
PMID: 39488259
4
PPA1 is overexpressed in epithelial ovarian cancer; higher levels correlate with advanced grades and poor survival; silencing PPA1 inhibits metastasis via Wnt/β-catenin pathway suppression
PMID: 29100310
5
PPA1 expression significantly elevated in lung and ovarian cancers; suppression increases apoptosis and decreases proliferation mediated by TP53 and p21 signaling
PMID: 27666431
6
PPA1 overexpressed in 51.3% of gastric cancers; associated with larger tumor size, nodal metastasis, advanced staging, and significantly reduced overall survival
PMID: 26722435
7
Genome-wide Mendelian randomization identified PPA1 as therapeutic target for diabetic microangiopathy with involvement in immune-related pathways
PMID: 40349847
8
Molecular docking screen identified devazepide and quinotolast as potential PPA1 inhibitors with high binding affinities for cancer therapeutic repurposing
PMID: 37733630
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.56Moderate
neuroinflammatory disorderOpen Targets
0.19Weak
neoplasmOpen Targets
0.11Weak
breast cancerOpen Targets
0.09Suggestive
infectionOpen Targets
0.08Suggestive
colorectal carcinomaOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
ovarian cancerOpen Targets
0.08Suggestive
lung cancerOpen Targets
0.06Suggestive
frozen shoulderOpen Targets
0.05Suggestive
coinfectionOpen Targets
0.05Suggestive
cytomegalovirus infectionOpen Targets
0.05Suggestive
Townes-Brocks syndromeOpen Targets
0.04Suggestive
prostate cancerOpen Targets
0.03Suggestive
glioblastomaOpen Targets
0.03Suggestive
hepatocellular carcinomaOpen Targets
0.03Suggestive
biliary tract diseaseOpen Targets
0.03Suggestive
cancerOpen Targets
0.03Suggestive
melanomaOpen Targets
0.03Suggestive
adenomaOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ACYP1Shared pathway100%ACYP2Shared pathway100%ATP5F1AProtein interaction100%ATP5PDProtein interaction100%ATP5MC1Protein interaction100%ATP5PFProtein interaction100%
Tissue Expression6 tissues
Brain
100%
Lung
85%
Liver
83%
Bone Marrow
69%
Heart
61%
Ovary
36%
Gene Interaction Network
Click a node to explore
PPA1ACYP1ACYP2ATP5F1AATP5PDATP5MC1ATP5PF
PROTEIN STRUCTURE
Preparing viewer…
PDB8J7Q · 1.69 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.00LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.67 [0.46–1.00]
RankingsWhere PPA1 stands among ~20K protein-coding genes
  • #2,940of 20,598
    Most Researched154 · top quartile
  • #9,689of 17,882
    Most Constrained (LOEUF)1.00
Genes detectedPPA1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
PPA1 promotes adipogenesis by regulating the stability of C/EBPs.
PMID: 38762596
Cell Death Differ · 2024
1.00
2
Cold-inducible PPA1 is critical for the adipocyte browning in mice.
PMID: 37549601
Biochem Biophys Res Commun · 2023
0.90
3
Genome-wide Mendelian randomization study identifies therapeutic targets for diabetic microangiopathy.
PMID: 40349847
Diabetes Res Clin Pract · 2025
0.80
4
TAT-PPA1 protects against oxidative stress-induced loss of dopaminergic neurons.
PMID: 39488259
Mol Cell Neurosci · 2024
0.70
5
Crystallographic and modeling study of the human inorganic pyrophosphatase 1: A potential anti-cancer drug target.
PMID: 33583053
Proteins · 2021
0.68