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4 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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PRRG2
proline rich and Gla domain 2
Chromosome 19 · 19q13.33
NCBI Gene: 5639Ensembl: ENSG00000126460.12HGNC: HGNC:9470UniProt: O14669
17PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingplasma membraneblood coagulationGO:0005615prostate carcinomaatrial fibrillationprostate cancerskin aging
✦AI Summary

PRRG2 (proline-rich Gla domain 2) is a vitamin K-dependent, cell-surface transmembrane protein essential for calcium homeostasis and hemostasis 1. The protein undergoes gamma-glutamyl carboxylation in a vitamin K-dependent manner and is predominantly localized to the cell surface with its Gla domain exposed extracellularly 1. PRRG2 contains tandem PY motifs that mediate binding to the transcriptional coactivator Yes-associated protein (YAP), suggesting involvement in signal transduction 1. Beyond its classical coagulation role, PRRG2 functions as a tumor suppressor in lung cancer pathogenesis. Transcriptional repression of PRRG2 by the oncoprotein ZBTB11 promotes YAP1 activation and lung cancer metastasis 2. PRRG2 belongs to a family of proline-rich Gla proteins with WW binding motifs that interact with numerous cytosolic proteins involved in diverse physiologic processes 3. Warfarin, a widely used anticoagulant that inhibits vitamin K-dependent carboxylation, may impair PRRG2-mediated signaling as an unintended consequence 1. These findings indicate PRRG2 functions beyond hemostasis, with emerging roles in cancer metastasis suppression and YAP-mediated cellular signaling.

Sources cited
1
PRRG2 is a vitamin K-dependent cell-surface protein with Gla domain exposed extracellularly; undergoes gamma-glutamyl carboxylation; binds YAP through PY motifs; warfarin may impair signaling
PMID: 17502622
2
ZBTB11 transcriptionally represses PRRG2 to promote YAP1 activation and lung cancer metastasis
PMID: 38355937
3
PRRG proteins have WW binding motifs and interact with cytosolic proteins involved in diverse physiologic processes; functions remain largely unknown
PMID: 23873930
⚠Limited data available — This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
prostate carcinomaOpen Targets
0.25Weak
atrial fibrillationOpen Targets
0.19Weak
prostate cancerOpen Targets
0.12Weak
skin agingOpen Targets
0.12Weak
hypothyroidismOpen Targets
0.09Suggestive
mathematical abilityOpen Targets
0.09Suggestive
mood disorderOpen Targets
0.07Suggestive
Abnormality of the skeletal systemOpen Targets
0.06Suggestive
hypoparathyroidism, familial isolated, 2Open Targets
0.05Suggestive
familial isolated hyperparathyroidismOpen Targets
0.05Suggestive
hyperparathyroidismOpen Targets
0.05Suggestive
pseudohypoparathyroidism type 2Open Targets
0.05Suggestive
adamantinomaOpen Targets
0.05Suggestive
ulna metaphyseal dysplasia syndromeOpen Targets
0.05Suggestive
intestinal hypomagnesemia 1Open Targets
0.05Suggestive
Primary hypomagnesemia with secondary hypocalcemiaOpen Targets
0.05Suggestive
FTH1-related iron overloadOpen Targets
0.04Suggestive
hemochromatosis type 5Open Targets
0.04Suggestive
blue diaper syndromeOpen Targets
0.04Suggestive
isolated hyperferritinemiaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PRRG1Shared pathway100%PRRG3Shared pathway100%PRRG4Shared pathway100%PROZShared pathway100%YAP1Protein interaction96%GGCXProtein interaction87%
Tissue Expression6 tissues
Liver
100%
Lung
43%
Heart
9%
Brain
6%
Ovary
4%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
PRRG2PRRG1PRRG3PRRG4PROZYAP1GGCX
PROTEIN STRUCTURE
Preparing viewer…
PDB9BVP · 3.30 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.29LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.91 [0.66–1.29]
RankingsWhere PRRG2 stands among ~20K protein-coding genes
  • #15,097of 20,598
    Most Researched17
  • #13,630of 17,882
    Most Constrained (LOEUF)1.29
Genes detectedPRRG2
Sources retrieved4 papers
Response time—
📄 Sources
4
1
Oncoprotein SET-associated transcription factor ZBTB11 triggers lung cancer metastasis.
PMID: 38355937
Nat Commun · 2024
1.00
2
Cellular localization and characterization of cytosolic binding partners for Gla domain-containing proteins PRRG4 and PRRG2.
PMID: 23873930
J Biol Chem · 2013
0.75
3
Contemporary Natural History and Management of Nonobstructive Hypertrophic Cardiomyopathy.
PMID: 27012399
J Am Coll Cardiol · 2016
0.50
4
Proline-rich Gla protein 2 is a cell-surface vitamin K-dependent protein that binds to the transcriptional coactivator Yes-associated protein.
PMID: 17502622
Proc Natl Acad Sci U S A · 2007
0.25