ITIH3 Gene - Inter-Alpha-Trypsin Inhibitor Heavy Chain 3 | Function, Disease & Expression

ITIH3 encodes a heavy chain component of the inter-alpha-trypsin inhibitor (ITI) family. The encoded protein is synthesized in the liver and secreted into plasma, where it forms complexes with other ITI heavy chains and bikunin. ITIH3 plays a critical role in extracellular matrix stabilization by covalently linking to hyaluronan, thereby contributing to tissue integrity and inflammation. It also functions as a serine protease inhibitor. Polymorphisms in ITIH3 have been associated with psychiatric disorders and cancer susceptibility.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Inter-alpha-trypsin inhibitor pathway (Reactome: R-HSA-166658)

• Extracellular matrix organization (Reactome: R-HSA-1474244)

• Hyaluronan metabolism (Reactome: R-HSA-2142850)

ITIH3 is a 90 kDa glycoprotein composed of 890 amino acids. It contains a VIT domain and a heavy chain domain typical of the ITI family. The protein is synthesized primarily in hepatocytes and secreted into the bloodstream. ITIH3 covalently attaches to hyaluronan via a transesterification reaction, stabilizing the extracellular matrix. It also inhibits serine proteases such as trypsin and plasmin. Post-translational modifications include N-glycosylation and proteolytic cleavage. The protein interacts with bikunin and other ITI heavy chains to form multimeric complexes.