MUC5B Gene - Mucin 5B: Function, Expression, and Disease Associations

MUC5B encodes a member of the mucin family of proteins, which are high-molecular-weight glycoproteins that form the major component of mucus. MUC5B is a gel-forming mucin primarily expressed in the respiratory tract, salivary glands, and cervical epithelium. It plays a critical role in mucociliary clearance, innate immune defense, and maintaining airway homeostasis. Variants in MUC5B are strongly associated with idiopathic pulmonary fibrosis (IPF) and other lung diseases.

Disease category	Pathophysiological mechanism	Genomic evidence
Idiopathic Pulmonary Fibrosis (IPF)	Promoter variant rs35705950 increases MUC5B expression in distal airways, disrupting epithelial repair and promoting fibrosis.	ClinVar, OMIM
Chronic Obstructive Pulmonary Disease (COPD)	MUC5B overexpression contributes to mucus hypersecretion and airway obstruction.	NCBI Gene, PubMed
Asthma	MUC5B is upregulated in airway epithelium, contributing to mucus plugging and airway hyperresponsiveness.	NCBI Gene, PubMed
Cystic Fibrosis	MUC5B is a major component of thickened mucus in CF airways, impairing clearance.	NCBI Gene, PubMed
Lung Cancer	Altered MUC5B expression is observed in non-small cell lung cancer, potentially influencing tumor microenvironment.	COSMIC, PubMed

MUC5B is a large, gel-forming mucin glycoprotein (approximately 600 kDa) that polymerizes via disulfide bonds to form a viscoelastic mucus gel. It is heavily O-glycosylated, providing hydration and protection to epithelial surfaces. In the lung, MUC5B is the predominant mucin in healthy airways and is essential for mucociliary clearance. Overexpression, driven by the rs35705950 variant, is the strongest genetic risk factor for idiopathic pulmonary fibrosis.