ITIH1 Gene - Inter-Alpha-Trypsin Inhibitor Heavy Chain 1
A key component of the inter-alpha-trypsin inhibitor family involved in extracellular matrix stabilization and inflammatory response.
Gene Information Card
| Symbol | ITIH1 |
|---|---|
| Full Name | Inter-Alpha-Trypsin Inhibitor Heavy Chain 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 3p21.1 |
| NCBI Gene ID | 3697 ncbi.nlm.nih.gov/gene/3697 |
| Ensembl ID | ENSG00000114770 |
| UniProt ID | P19827 |
| OMIM ID | 147270 |
| HGNC ID | 6167 |
| Aliases | ITIH, IATIH, SHAP, H1P |
Description
ITIH1 encodes a heavy chain subunit 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 chains and the light chain bikunin. ITIH1 plays a critical role in extracellular matrix stabilization by covalently linking to hyaluronan, thereby contributing to tissue integrity and inflammatory responses. Mutations and altered expression of ITIH1 have been implicated in various cancers and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Downregulation of ITIH1 may promote tumor progression and metastasis. | COSMIC; PMID: 25691885 |
| Pancreatic cancer | Reduced ITIH1 expression associated with poor prognosis. | COSMIC; PMID: 28411376 |
| Ovarian cancer | ITIH1 hypermethylation and silencing contribute to tumorigenesis. | COSMIC; PMID: 21947009 |
| Inflammatory bowel disease | ITIH1 involved in extracellular matrix remodeling during inflammation. | UniProt; PMID: 20877624 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 123.4 | High |
| Pancreas | 12.1 | Low |
| Kidney | 8.5 | Low |
| Lung | 5.2 | Not detected |
| Brain | 1.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 89.7 | Hepatocellular carcinoma cell line |
| MCF7 | 2.1 | Breast cancer cell line |
| A549 | 1.5 | Lung carcinoma cell line |
| K562 | 0.8 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T | Missense | 0.02% | p.Pro412Ser; uncertain significance |
| c.567G>A | Nonsense | 0.01% | p.Trp189*; predicted loss of function |
| c.890_891insA | Frameshift | 0.005% | p.Glu297fs; loss of function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in ITIH1 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 ITIH1.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for ITIH1.
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)
• Hyaluronan metabolism (Reactome: R-HSA-216083)
Protein Summary
ITIH1 is a 911-amino acid heavy chain glycoprotein (UniProt P19827) that is primarily synthesized in the liver and secreted into plasma. It forms covalent complexes with other ITI heavy chains and the light chain bikunin via a chondroitin sulfate linkage. The protein is involved in stabilizing the extracellular matrix by cross-linking hyaluronan, and it also acts as a serine protease inhibitor. Post-translational modifications include glycosylation and proteolytic cleavage.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ITIH1 Knockout HEK293 Cell Line | EDJ-KQ5010 | Human | 3697 | Details Get a Quote |
| ITIH1 Knockout HeLa Cell Line | EDJ-KQ53683 | Human | 3697 | Details Get a Quote |
| ITIH1 Knockout A-549 Cell Line | EDJ-KQ62159 | Human | 3697 | Details Get a Quote |
| ITIH1 Knockout HCT 116 Cell Line | EDJ-KQ70648 | Human | 3697 | Details Get a Quote |
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