SPINT2: Serine Peptidase Inhibitor, Kunitz Type 2
A key regulator of hepatocyte growth factor activation and epithelial integrity
Gene Information Card
| Symbol | SPINT2 |
|---|---|
| Full Name | Serine Peptidase Inhibitor, Kunitz Type 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.2 |
| NCBI Gene ID | 10653 ncbi.nlm.nih.gov/gene/10653 |
| Ensembl ID | ENSG00000167642 |
| UniProt ID | O43291 |
| OMIM ID | 605124 |
| HGNC ID | 11247 |
| Aliases | HAI-2, PB, DIAR3, KOP |
Description
SPINT2 encodes a transmembrane protein that belongs to the Kunitz-type serine protease inhibitor family. It inhibits hepatocyte growth factor activator (HGFA) and other trypsin-like serine proteases, thereby regulating pericellular proteolysis and growth factor signaling. The protein is essential for maintaining epithelial barrier function and is implicated in development, sodium homeostasis, and tumor suppression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital Sodium Diarrhea (DIAR3) | Loss-of-function mutations in SPINT2 reduce inhibition of serine proteases, leading to excessive proteolytic activity and impaired sodium absorption in the intestine. | ClinVar, OMIM |
| Colorectal Cancer | Reduced SPINT2 expression or promoter hypermethylation leads to increased HGFA activity, promoting HGF/c-Met signaling and tumor progression. | COSMIC, NCBI |
| Hepatocellular Carcinoma | Downregulation of SPINT2 correlates with poor prognosis; loss of inhibition of matriptase and hepsin enhances invasive growth. | COSMIC, PubMed |
| Prostate Cancer | Epigenetic silencing of SPINT2 contributes to increased matriptase activity and tumor invasion. | COSMIC, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 11.2 | Medium |
| Small Intestine | 9.8 | Medium |
| Colon | 8.5 | Medium |
| Liver | 6.3 | Low |
| Lung | 5.1 | Low |
| Pancreas | 4.7 | Low |
| Prostate | 3.9 | Low |
| Breast | 2.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 (Colorectal) | 12.5 | High expression; used in intestinal barrier studies |
| HepG2 (Liver) | 7.2 | Moderate expression |
| A549 (Lung) | 4.1 | Low expression |
| PC-3 (Prostate) | 3.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon; associated with congenital sodium diarrhea |
| c.161G>A (p.Cys54Tyr) | Missense | Rare | Disrupts Kunitz domain; loss of inhibitory function |
| c.298C>T (p.Arg100*) | Nonsense | Rare | Premature stop; loss of function |
| c.407_408del (p.Glu136Glyfs*13) | Frameshift | Rare | Truncated protein; loss of function |
| c.557G>A (p.Arg186His) | Missense | Rare | Reduced inhibitory activity; associated with diarrhea |
Mutation functional classification
Loss of Function (LOF)
Most reported SPINT2 mutations are loss-of-function, leading to reduced inhibition of serine proteases (e.g., matriptase, HGFA). This results in uncontrolled pericellular proteolysis and is the primary mechanism in congenital sodium diarrhea.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SPINT2.
Dominant Negative (DN)
No dominant-negative mutations have been described for SPINT2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Hepatocyte growth factor (HGF) signaling pathway
• Matriptase activation pathway
• Extracellular matrix remodeling
• Proteolysis and cell migration
Protein Summary
SPINT2 (HAI-2) is a 252-amino acid transmembrane protein containing two Kunitz domains. It is a potent inhibitor of serine proteases such as HGFA, matriptase, and hepsin. The protein is expressed on the cell surface and in the extracellular matrix, where it regulates pericellular proteolysis, growth factor activation, and epithelial integrity. Loss of SPINT2 function leads to excessive protease activity, contributing to congenital sodium diarrhea and promoting cancer invasion and metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SPINT2 Knockout HEK293 Cell Line | EDJ-KQ2746 | Human | 10653 | Details Get a Quote |
| SPINT2 Knockout A-549 Cell Line | EDJ-KQ23628 | Human | 10653 | Details Get a Quote |
| SPINT2 Knockout HCT 116 Cell Line | EDJ-KQ23629 | Human | 10653 | Details Get a Quote |
| SPINT2 Knockout HeLa Cell Line | EDJ-KQ23630 | Human | 10653 | Details Get a Quote |
