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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PRAG1
PEAK1 related, kinase-activating pseudokinase 1
Chromosome 8 · 8p23.1
NCBI Gene: 157285Ensembl: ENSG00000275342.7HGNC: HGNC:25438UniProt: Q86YV5
35PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcell migrationidentical protein bindingfocal adhesionAbnormality of the skeletal systemhypothyroidismasthmanontoxic goiter
✦AI Summary

PRAG1 (PEAK1-related kinase-activating pseudokinase 1) is a catalytically inactive scaffold protein that regulates cell morphology, migration, and stress responses through protein-protein interactions rather than kinase activity. PRAG1 forms dynamic phase-separated condensates mediated by its αN and αJ helices, which drive cell contraction under stress conditions 1. The protein functions as a nodal signaling hub: it activates Src family kinase signaling by sequestering CSK (a negative regulator) away from its targets, and promotes epithelial-mesenchymal transition (EMT) by binding FBXO11 and stabilizing SNAIL1, a master EMT transcription factor 2. In colorectal cancer, high PRAG1 expression correlates with poor prognosis and promotes cell invasion through ABL kinase activation and filopodia formation 3. Disease relevance spans multiple conditions: PRAG1 genetic variants associate with IgA nephropathy (rs143409664) 4, cardiac allograft vasculopathy (rs11785239) 5, asthma bronchodilator response (rs4840337) 6, and major depressive disorder treatment response 7. Notably, aberrant PRAG1 condensation occurs in Parkinson's disease dopaminergic neurons, suggesting links between PRAG1 dysfunction and neurodegenerative pathology 1. These findings establish PRAG1 as a multifunctional adapter protein controlling diverse cellular processes with significant clinical implications.

Sources cited
1
PRAG1 promotes cholangiocyte EMT and liver fibrosis in biliary atresia by binding FBXO11 and stabilizing SNAIL1 protein
PMID: 40743806
2
PRAG1 forms phase-separated condensates that mediate cell contraction under stress, with aberrant condensation observed in Parkinson's disease neurons
PMID: 40149915
3
High PRAG1 expression associates with poor prognosis in colorectal cancer; PEAK2/PRAG1 activates ABL kinase and promotes cell invasion
PMID: 35740644
4
PRAG1 rs143409664 variant shows strongest association with IgA nephropathy in pediatric patients
PMID: 37958966
5
PRAG1 rs11785239 SNP associates with cardiac allograft vasculopathy intima thickness progression
PMID: 36598310
6
PRAG1 rs4840337 shows age-dependent interaction with bronchodilator response in asthma
PMID: 33477890
7
PRAG1 locus associates with major depressive disorder SSRI remission outcomes
PMID: 29559929
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.48Moderate
hypothyroidismOpen Targets
0.44Moderate
asthmaOpen Targets
0.43Moderate
nontoxic goiterOpen Targets
0.40Moderate
denturesOpen Targets
0.36Weak
joint diseaseOpen Targets
0.36Weak
glaucomaOpen Targets
0.36Weak
Increased blood pressureOpen Targets
0.35Weak
hypertensionOpen Targets
0.34Weak
IGA glomerulonephritisOpen Targets
0.34Weak
myxedemaOpen Targets
0.34Weak
multinodular goiterOpen Targets
0.33Weak
injuryOpen Targets
0.33Weak
chronic obstructive pulmonary diseaseOpen Targets
0.32Weak
gastroesophageal reflux diseaseOpen Targets
0.32Weak
mathematical abilityOpen Targets
0.32Weak
response to selective serotonin reuptake inhibitorOpen Targets
0.31Weak
Odontogenic CystOpen Targets
0.30Weak
Hashimoto's thyroiditisOpen Targets
0.30Weak
systemic lupus erythematosusOpen Targets
0.29Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CSKProtein interaction85%RND2Protein interaction81%PEAK3Shared pathway29%PEAK1Shared pathway20%FMNL2Shared pathway20%ARHGAP18Shared pathway20%
Tissue Expression6 tissues
Lung
100%
Heart
94%
Brain
92%
Ovary
66%
Liver
51%
Bone Marrow
19%
Gene Interaction Network
Click a node to explore
PRAG1CSKRND2PEAK3PEAK1FMNL2ARHGAP18
PROTEIN STRUCTURE
Preparing viewer…
PDB5VE6 · 2.95 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.29LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.08 [0.91–1.29]
RankingsWhere PRAG1 stands among ~20K protein-coding genes
  • #11,044of 20,598
    Most Researched35
  • #13,636of 17,882
    Most Constrained (LOEUF)1.29
Genes detectedPRAG1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PRAG1 promotes cholangiocyte epithelial-mesenchymal transition and liver fibrosis in biliary atresia.
PMID: 40743806
Biochim Biophys Acta Mol Basis Dis · 2025
1.00
2
Candidate Genes for IgA Nephropathy in Pediatric Patients: Exome-Wide Association Study.
PMID: 37958966
Int J Mol Sci · 2023
0.90
3
Role of genetics in the development of cardiac allograft vasculopathy.
PMID: 36598310
Bratisl Lek Listy · 2023
0.80
4
PRAG1 Condensation Drives Cell Contraction Under Stress.
PMID: 40149915
Biomolecules · 2025
0.70
5
Oncogenic Signalling of PEAK2 Pseudokinase in Colon Cancer.
PMID: 35740644
Cancers (Basel) · 2022
0.60