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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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PRR4
proline rich 4
Chromosome 12 · 12p13.2
NCBI Gene: 11272Ensembl: ENSG00000111215.13HGNC: HGNC:18020UniProt: Q16378
27PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingGO:0005615visual perceptionextracellular regionFamilial prostate cancerprostate cancernon-small cell lung carcinomaasthma
✦AI Summary

PRR4 (proline-rich 4) is a protein synthesized in acinar cells of lacrimal and salivary glands with multifaceted roles in ocular and systemic biology. As a component of tear and salivary proteomes, PRR4 exhibits antimicrobial properties that protect the ocular surface and oral cavity 1. The protein undergoes complex post-translational modifications including methylation, acetylation, oxidation, and pyroglutamate formation, generating multiple isoforms with molecular weights of 17-30 kDa in tears 2. In healthy salivary glands, a specific PRR4+CST3+WFDC2- seromucous acinar cell population exists that is selectively lost in Sjögren's disease due to targeting by GZMK+CD8+ T cells, contributing to exocrine gland dysfunction 34. PRR4 serves as a biomarker for ocular surface disorders, with expression detected in dry eye disease and ocular allergy contexts 5. In laryngeal cancer, PRR4 expression is significantly reduced in tumor tissues (72.2% of cases), suggesting a protective role against carcinogenesis 1. Additionally, circRNA PRH1-PRR4 functions as a competing endogenous RNA regulating non-small-cell lung cancer progression via the miR-877-5p/RAB3D pathway 6. PRR4 methylation patterns show sex-specific age-dependent changes 7, indicating epigenetic regulation relevant to aging and longevity.

Sources cited
1
PRR4 is synthesized in lacrimal gland acinar cells and functions as an antimicrobial protein; PRR4 expression is decreased in 72.2% of laryngeal tumors
PMID: 29541239
2
PRR4 exists in multiple isoforms (17-30 kDa) with complex post-translational modifications in tears including methylation, acetylation, oxidation, and pyroglutamate formation
PMID: 24782455
3
PRR4+CST3+WFDC2- seromucous acinar cells are selectively targeted and lost in Sjögren's disease
PMID: 38196575
4
PRR4+ seromucous acinar cell population is selectively lost in Sjögren's disease in association with GZMK+CD8+ T cell activity
PMID: 41162286
5
PRR4 is identified as a biomarker in ocular surface disorders including dry eye disease and ocular allergy
PMID: 37876509
6
CircRNA PRH1-PRR4 regulates non-small-cell lung cancer progression through the miR-877-5p/RAB3D pathway
PMID: 35076987
7
PRR4 methylation patterns show sex-specific age-dependent changes relevant to aging
PMID: 33276343
Disease Associationsⓘ20
Familial prostate cancerOpen Targets
0.11Weak
prostate cancerOpen Targets
0.11Weak
non-small cell lung carcinomaOpen Targets
0.07Suggestive
asthmaOpen Targets
0.03Suggestive
COVID-19Open Targets
0.02Suggestive
neoplasmOpen Targets
0.02Suggestive
post-transplant lymphoproliferative diseaseOpen Targets
0.01Suggestive
Down syndromeOpen Targets
0.01Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.01Suggestive
dry eye syndromeOpen Targets
0.01Suggestive
bronchiectasisOpen Targets
0.01Suggestive
head and neck squamous cell carcinomaOpen Targets
0.01Suggestive
lupus nephritisOpen Targets
0.01Suggestive
infectionOpen Targets
0.01Suggestive
laryngeal neoplasmOpen Targets
0.01Suggestive
colorectal cancerOpen Targets
0.00Suggestive
Sjogren syndromeOpen Targets
0.00Suggestive
conjunctivitisOpen Targets
0.00Suggestive
Nasal Cavity PolypOpen Targets
0.00Suggestive
systemic lupus erythematosusOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
IMPG1Shared pathway100%ROM1Shared pathway100%NYXShared pathway100%IMPG2Shared pathway100%RAXShared pathway100%AIPL1Shared pathway100%
Tissue Expression6 tissues
Ovary
100%
Liver
83%
Lung
45%
Brain
29%
Heart
24%
Bone Marrow
12%
Gene Interaction Network
Click a node to explore
PRR4IMPG1ROM1NYXIMPG2RAXAIPL1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q16378
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.78LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.96 [0.49–1.78]
RankingsWhere PRR4 stands among ~20K protein-coding genes
  • #12,653of 20,598
    Most Researched27
  • #16,463of 17,882
    Most Constrained (LOEUF)1.78
Genes detectedPRR4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Biomarkers of ocular allergy and dry eye disease.
PMID: 37876509
Rom J Ophthalmol · 2023
1.00
2
Spatial Analysis of Hereditary Diffuse Gastric Cancer Reveals Indolent Phenotype of Signet Ring Cell Precursors.
PMID: 40192595
Mol Cancer Res · 2025
0.90
3
GZMK
PMID: 41162286
Ann Rheum Dis · 2025
0.80
4
GZMK+CD8+ T cells Target A Specific Acinar Cell Type in Sjögren's Disease.
PMID: 38196575
Res Sq · 2024
0.70
5
PMID: 29541239
Oncol Lett · 2018
0.60