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28 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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MUC4
mucin 4, cell surface associated
Chromosome 3 · 3q29
NCBI Gene: 4585Ensembl: ENSG00000145113HGNC: HGNC:7514UniProt: A0A0G2JS65
204PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular exosomemaintenance of gastrointestinal epitheliumGO:0005615vesicleneurodegenerative diseaseCOVID-19joint diseaseresponse to COVID-19 vaccine
✦AI Summary

MUC4 is a membrane-bound mucin that functions as a highly glycosylated epithelial protection factor and cellular signaling modulator. As a major mucus component, MUC4 protects epithelial surfaces and promotes epithelial renewal and differentiation 1. Beyond its structural role, MUC4 acts as an intramembrane ligand for ERBB2, regulating proliferation and differentiation through phosphorylation cascades 2. MUC4 expression is upregulated during mucociliary differentiation of airway epithelia in a retinoic acid-dependent manner 3 and is induced in metaplastic pit cells during Helicobacter pylori-driven gastric inflammation 4. In cancer pathology, MUC4 is a clinically significant marker with dual importance. It is rarely expressed in normal pancreas but extensively overexpressed in pancreatic tumors, making it a valuable tumor-associated antigen for vaccine development 5. MUC4 expression correlates with aggressive tumor behavior and poor prognosis in various neoplasms 6. The protein's upregulation in precancerous lesions and association with enhanced proliferation in gastric cancer 4 suggest its utility in early cancer detection. MUC4 has therapeutic potential as an immunotherapy target and biomarker for evaluating malignancy potential, particularly in pancreatobiliary and gastric cancers 6, 5.

Sources cited
1
MUC4 is a membrane-bound mucin constituting a major component of mucus covering epithelial surfaces, playing important roles in epithelium protection and epithelial renewal and differentiation
PMID: 10880978
2
MUC4 acts as a ligand/modulator of ErbB2 receptor tyrosine kinase, regulating phosphorylation and modulating cell apoptosis through multiple mechanisms
PMID: 20001800
3
MUC4 expression is upregulated during mucociliary differentiation of human airway epithelial cells in a retinoic acid-dependent manner
PMID: 10100990
4
MUC4 expression is significantly associated with proliferation in human gastric cancer and is expressed in metaplastic pit cells driven by Helicobacter pylori-dependent inflammation
PMID: 37674528
5
MUC4 is overexpressed in pancreatic tumors but not detected in normal pancreas, making it an attractive tumor-associated antigen for vaccine development in pancreatic cancer immunotherapy
PMID: 31952903
6
MUC4 expression correlates with aggressive behavior and poor outcome of human neoplasms, with potential clinical utility for early detection and evaluation of malignancy potential in pancreatobiliary neoplasms
PMID: 22126377
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.42Moderate
COVID-19Open Targets
0.26Weak
joint diseaseOpen Targets
0.24Weak
response to COVID-19 vaccineOpen Targets
0.24Weak
aortic stenosisOpen Targets
0.24Weak
aortic valve calcificationOpen Targets
0.24Weak
ovarian dysfunctionOpen Targets
0.24Weak
gliomaOpen Targets
0.20Weak
oral squamous cell carcinomaOpen Targets
0.20Weak
lung adenocarcinomaOpen Targets
0.20Weak
papillary thyroid carcinomaOpen Targets
0.20Weak
breast carcinomaOpen Targets
0.20Weak
non-small cell lung carcinomaOpen Targets
0.20Weak
gastric adenocarcinomaOpen Targets
0.20Weak
esophageal squamous cell carcinomaOpen Targets
0.20Weak
urinary bladder carcinomaOpen Targets
0.19Weak
melanomaOpen Targets
0.19Weak
diffuse large B-cell lymphomaOpen Targets
0.19Weak
acute lymphoblastic leukemiaOpen Targets
0.19Weak
head and neck squamous cell carcinomaOpen Targets
0.19Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EGFRProtein interaction100%MUC1Protein interaction100%MUC15Protein interaction93%MUC12Protein interaction93%MUC20Protein interaction93%MUC16Protein interaction93%
Tissue Expression6 tissues
Lung
100%
Liver
35%
Ovary
23%
Brain
12%
Bone Marrow
6%
Heart
4%
Gene Interaction Network
Click a node to explore
MUC4EGFRMUC1MUC15MUC12MUC20MUC16
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q99102
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.95LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.85 [0.75–0.95]
RankingsWhere MUC4 stands among ~20K protein-coding genes
  • #2,059of 20,598
    Most Researched204 · top 10%
  • #8,927of 17,882
    Most Constrained (LOEUF)0.95
Genes detectedMUC4
Sources retrieved28 papers
Response time—
📄 Sources
28▼
1
Dynamic Imaging of RNA in Living Cells by CRISPR-Cas13 Systems.
PMID: 31757757
Mol Cell · 2019
1.00
2
Dynamic imaging of genomic loci in living human cells by an optimized CRISPR/Cas system.
PMID: 24360272
Cell · 2013
0.90
3
Purified human breast milk MUC1 and MUC4 inhibit human immunodeficiency virus.
PMID: 24503884
Neonatology · 2014
0.80
4
Muc4/MUC4 functions and regulation in cancer.
PMID: 20001800
Future Oncol · 2009
0.80
5
Circadian disruption reduces MUC4 expression via the clock molecule BMAL1 during dry eye development.
PMID: 38956298
Exp Mol Med · 2024
0.76