SPINT1: Serine Peptidase Inhibitor, Kunitz Type 1
A key regulator of hepatocyte growth factor activation and tumor suppression
Gene Information Card
| Symbol | SPINT1 |
|---|---|
| Full Name | Serine Peptidase Inhibitor, Kunitz Type 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q15.1 |
| NCBI Gene ID | 6692 ncbi.nlm.nih.gov/gene/6692 |
| Ensembl ID | ENSG00000166145 |
| UniProt ID | O43278 |
| OMIM ID | 605123 |
| HGNC ID | 11246 |
| Aliases | HAI-1, HAI, HAI1, MANSC2 |
Description
SPINT1 encodes hepatocyte growth factor activator inhibitor type 1 (HAI-1), a Kunitz-type serine protease inhibitor that regulates the activation of hepatocyte growth factor (HGF) and other proteases. It plays a critical role in tissue regeneration, cell migration, and tumor suppression. Loss of SPINT1 function is associated with various cancers and renal diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Reduced SPINT1 expression leads to increased HGF activation and MET signaling, promoting invasion and metastasis | PMID: 21502545 |
| Breast cancer | Epigenetic silencing of SPINT1 correlates with poor prognosis and aggressive tumor behavior | PMID: 23233736 |
| Renal tubular dysgenesis | Biallelic loss-of-function mutations in SPINT1 cause severe renal developmental defects | PMID: 23972370 |
| Pancreatic cancer | Downregulation of SPINT1 enhances matriptase activity, contributing to tumor progression | PMID: 20010872 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Pancreas | 6.1 | Low |
| Prostate | 4.7 | Low |
| Lung | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.0 | Hepatocellular carcinoma cell line |
| MCF7 | 7.8 | Breast cancer cell line |
| PANC-1 | 5.4 | Pancreatic cancer cell line |
| HEK293 | 4.1 | Embryonic kidney cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon, likely loss of function |
| c.205C>T (p.Arg69Trp) | Missense | <0.01% | Impaired inhibitor activity |
| c.497G>A (p.Arg166Gln) | Missense | <0.01% | Reduced binding to target proteases |
| c.1045C>T (p.Arg349*) | Nonsense | <0.01% | Premature truncation, loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported SPINT1 mutations are loss-of-function, leading to reduced HAI-1 activity and dysregulated protease signaling.
Gain of Function (GOF)
No gain-of-function mutations have been documented for SPINT1.
Dominant Negative (DN)
No dominant-negative mutations have been reported for SPINT1.
View complete mutation data：
Gene Ontology (GO)
| • serine-type endopeptidase inhibitor activity | • hepatocyte growth factor binding |
| • extracellular region | • negative regulation of proteolysis |
| • cell migration |
Pathways
• HGF-MET signaling pathway
• Matriptase activation pathway
• Kunitz-type protease inhibitor pathway
Protein Summary
The SPINT1 protein (HAI-1) is a 527-amino acid transmembrane glycoprotein containing two Kunitz domains that inhibit serine proteases such as HGF activator and matriptase. It is expressed on the cell surface and in the extracellular matrix, where it regulates pericellular proteolysis and growth factor signaling. HAI-1 is essential for maintaining epithelial integrity and suppressing tumor invasion.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPINT1 Knockout HEK293 Cell Line | EDJ-KQ5834 | Human | 6692 | Details Get a Quote |
| SPINT1 Knockout A-549 Cell Line | EDJ-KQ29280 | Human | 6692 | Details Get a Quote |
| SPINT1 Knockout HCT 116 Cell Line | EDJ-KQ29281 | Human | 6692 | Details Get a Quote |
| SPINT1 Knockout HeLa Cell Line | EDJ-KQ29282 | Human | 6692 | Details Get a Quote |
