ITIH2: Inter-Alpha-Trypsin Inhibitor Heavy Chain 2
A serine protease inhibitor involved in extracellular matrix stabilization and inflammatory response
Gene Information Card
| Symbol | ITIH2 |
|---|---|
| Full Name | Inter-Alpha-Trypsin Inhibitor Heavy Chain 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 10p14 |
| NCBI Gene ID | 3698 ncbi.nlm.nih.gov/gene/3698 |
| Ensembl ID | ENSG00000151655 |
| UniProt ID | P19823 |
| OMIM ID | 147670 |
| HGNC ID | 6168 |
| Aliases | H2P, ITI-HC2, SHAP |
Description
ITIH2 encodes a heavy chain subunit of the inter-alpha-trypsin inhibitor (ITI) family, a group of serine protease inhibitors that stabilize the extracellular matrix by covalently binding hyaluronan. The protein is synthesized in the liver and secreted into plasma, where it participates in inflammation, tissue repair, and cancer progression. Mutations or altered expression of ITIH2 have been implicated in inflammatory disorders and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Downregulation of ITIH2 may promote tumor invasion and metastasis by altering extracellular matrix composition. | PMID: 25944712 |
| Pancreatic cancer | Reduced ITIH2 expression correlates with poor prognosis and increased metastatic potential. | PMID: 28476880 |
| Ovarian cancer | ITIH2 hypermethylation leads to silencing, contributing to tumor progression. | PMID: 23382210 |
| Inflammatory bowel disease | Altered ITI complex levels may modulate mucosal inflammation. | PMID: 20628061 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 45.2 | High |
| Pancreas | 12.8 | Medium |
| Kidney | 8.5 | Medium |
| Lung | 5.1 | Low |
| Breast | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 42.1 | Hepatocellular carcinoma cell line |
| MCF7 | 2.8 | Breast cancer cell line |
| A549 | 4.5 | Lung carcinoma cell line |
| PANC-1 | 6.3 | Pancreatic cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412Cys) | Missense | <0.01% | Unknown functional impact; reported in ClinVar |
| c.567G>A (p.Trp189*) | Nonsense | <0.01% | Predicted loss of function |
| c.890_891insA | Frameshift | <0.01% | Predicted loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in ITIH2 are predicted to cause loss of function, potentially impairing extracellular matrix stabilization.
Gain of Function (GOF)
No gain-of-function mutations have been reported for ITIH2.
Dominant Negative (DN)
No dominant-negative mutations have been described for ITIH2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Inter-alpha-trypsin inhibitor complex formation (Reactome: R-HSA-8957275)
• Extracellular matrix organization (Reactome: R-HSA-1474244)
• Degradation of the extracellular matrix (Reactome: R-HSA-1474228)
Protein Summary
ITIH2 (Inter-Alpha-Trypsin Inhibitor Heavy Chain 2) is a 946-amino-acid glycoprotein (UniProt P19823) primarily synthesized in the liver. It functions as a heavy chain component of the inter-alpha-trypsin inhibitor (ITI) complex, which covalently attaches to hyaluronan via a unique ester bond, stabilizing the extracellular matrix. The protein contains a VWA domain and a Kunitz-type serine protease inhibitor domain. ITIH2 is involved in acute-phase responses, tissue remodeling, and inflammation. Reduced expression is observed in several cancers, suggesting a tumor-suppressive role.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ITIH2 Knockout HEK293 Cell Line | EDJ-KQ4229 | Human | 3698 | Details Get a Quote |
| ITIH2 Knockout HeLa Cell Line | EDJ-KQ53684 | Human | 3698 | Details Get a Quote |
| ITIH2 Knockout A-549 Cell Line | EDJ-KQ62160 | Human | 3698 | Details Get a Quote |
| ITIH2 Knockout HCT 116 Cell Line | EDJ-KQ70649 | Human | 3698 | Details Get a Quote |
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