Name | serine peptidase inhibitor, Kunitz type 1 |
Description | The protein encoded by this gene is a member of the Kunitz family of serine protease inhibitors. The protein is a potent inhibitor specific for HGF activator and is thought to be involved in the regulation of the proteolytic activation of HGF in injured tissues. Alternative splicing results in multiple variants encoding different isoforms. [provided by RefSeq, Jul 2008] |
Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSPINT1, also known as hepatocyte growth factor activator inhibitor‐1 (HAI‐1), is a membrane‐bound, Kunitz‐type serine protease inhibitor that plays an essential role in maintaining the balance of pericellular proteolysis. It functions by binding and reversibly inhibiting several trypsin‐like serine proteases—including hepatocyte growth factor activator (HGFA), matriptase, hepsin, and prostasin—to regulate the proteolytic activation of growth factors such as pro–HGF, as well as by acting as a cell‐surface reservoir for active proteases. The inhibitor is synthesized as an integral membrane protein that may be shed from the cell surface under inflammatory or tissue injury conditions, a process that modulates its inhibitory activity and regulates signal transduction pathways at epithelial surfaces."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn various cancer models, alterations in SPINT1 expression or its ratio relative to target proteases such as matriptase are closely linked to tumor progression, invasion, and metastasis. Loss or down‐regulation of SPINT1 in carcinoma cells has been shown to trigger epithelial–mesenchymal transition (EMT) through deregulated proteolytic activity and signaling cascades (involving substrates like pro–HGF and PAR‐2) that ultimately enhance motility and invasiveness. In several epithelial malignancies—including pancreatic, prostate, and cervical cancers—the aberrant expression of SPINT1 is correlated with reduced cell–cell adhesion, increased protease activity on the cell surface, and a more aggressive tumor phenotype."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "28"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in protease inhibition, SPINT1 is also involved in fine‐tuning cellular responses in diverse tissues. Structural and biochemical studies reveal that its configuration and shedding dynamics are critical for modulating interactions with both membrane‐bound and soluble proteases, thereby influencing downstream signaling pathways such as HGF/MET and p38 MAPK. In normal tissues including skin, placenta, and the gastrointestinal tract—and during processes like differentiation, inflammation, and tissue repair—the regulatory actions of SPINT1 help maintain epithelial integrity. Moreover, the emerging understanding of its molecular interactions has spurred interest in targeting SPINT1–protease networks as a therapeutic strategy in conditions ranging from placental insufficiency to cancer metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "29", "end_ref": "45"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "H Kataoka, T Shimomura, T Kawaguchi, et al. 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Synonyms | MANSC2, HAI1, HAI |
Proteins | SPIT1_HUMAN |
NCBI Gene ID | 6692 |
API | |
Download Associations | |
Predicted Functions |
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Co-expressed Genes |
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Expression in Tissues and Cell Lines |
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SPINT1 has 6,444 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 105 datasets.
Click the + buttons to view associations for SPINT1 from the datasets below.
If available, associations are ranked by standardized value
Dataset | Summary | |
---|---|---|
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of SPINT1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset. | |
Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles | tissues with high or low expression of SPINT1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset. | |
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of SPINT1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq | tissue samples with high or low expression of SPINT1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset. | |
BioGPS Cell Line Gene Expression Profiles | cell lines with high or low expression of SPINT1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset. | |
BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of SPINT1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of SPINT1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset. | |
CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of SPINT1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
CCLE Cell Line Gene Expression Profiles | cell lines with high or low expression of SPINT1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
CCLE Cell Line Proteomics | Cell lines associated with SPINT1 protein from the CCLE Cell Line Proteomics dataset. | |
CellMarker Gene-Cell Type Associations | cell types associated with SPINT1 gene from the CellMarker Gene-Cell Type Associations dataset. | |
ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of SPINT1 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
ChEA Transcription Factor Targets | transcription factors binding the promoter of SPINT1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. | |
ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of SPINT1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of SPINT1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing SPINT1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing SPINT1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
COMPARTMENTS Experimental Protein Localization Evidence Scores | cellular components containing SPINT1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset. | |
COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 | cellular components containing SPINT1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset. | |
COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with SPINT1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset. | |
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with SPINT1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
COSMIC Cell Line Gene Mutation Profiles | cell lines with SPINT1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
CTD Gene-Chemical Interactions | chemicals interacting with SPINT1 gene/protein from the curated CTD Gene-Chemical Interactions dataset. | |
CTD Gene-Disease Associations | diseases associated with SPINT1 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
DeepCoverMOA Drug Mechanisms of Action | small molecule perturbations with high or low expression of SPINT1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset. | |
DepMap CRISPR Gene Dependency | cell lines with fitness changed by SPINT1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with SPINT1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset. | |
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with SPINT1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
DisGeNET Gene-Disease Associations | diseases associated with SPINT1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
DisGeNET Gene-Phenotype Associations | phenotypes associated with SPINT1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at SPINT1 gene from the ENCODE Histone Modification Site Profiles dataset. | |
ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of SPINT1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
ENCODE Transcription Factor Targets | transcription factors binding the promoter of SPINT1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells | PubMedIDs of publications reporting gene signatures containing SPINT1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
GAD Gene-Disease Associations | diseases associated with SPINT1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
GAD High Level Gene-Disease Associations | diseases associated with SPINT1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset. | |
GeneRIF Biological Term Annotations | biological terms co-occuring with SPINT1 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing SPINT1 from the GeneSigDB Published Gene Signatures dataset. | |
GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of SPINT1 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset. | |
GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of SPINT1 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of SPINT1 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of SPINT1 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of SPINT1 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of SPINT1 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
GlyGen Glycosylated Proteins | ligands (chemical) binding SPINT1 protein from the GlyGen Glycosylated Proteins dataset. | |
GO Biological Process Annotations 2015 | biological processes involving SPINT1 gene from the curated GO Biological Process Annotations 2015 dataset. | |
GO Biological Process Annotations 2023 | biological processes involving SPINT1 gene from the curated GO Biological Process Annotations 2023 dataset. | |
GO Biological Process Annotations 2025 | biological processes involving SPINT1 gene from the curated GO Biological Process Annotations2025 dataset. | |
GO Cellular Component Annotations 2015 | cellular components containing SPINT1 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
GO Molecular Function Annotations 2015 | molecular functions performed by SPINT1 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
GO Molecular Function Annotations 2023 | molecular functions performed by SPINT1 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
GO Molecular Function Annotations 2025 | molecular functions performed by SPINT1 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
GTEx eQTL 2025 | SNPs regulating expression of SPINT1 gene from the GTEx eQTL 2025 dataset. | |
GTEx Tissue Gene Expression Profiles | tissues with high or low expression of SPINT1 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of SPINT1 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
GTEx Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of SPINT1 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset. | |
GTEx Tissue-Specific Aging Signatures | tissue samples with high or low expression of SPINT1 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset. | |
GWASdb SNP-Disease Associations | diseases associated with SPINT1 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset. | |
GWASdb SNP-Phenotype Associations | phenotypes associated with SPINT1 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset. | |
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of SPINT1 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
HPA Cell Line Gene Expression Profiles | cell lines with high or low expression of SPINT1 gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset. | |
HPA Tissue Gene Expression Profiles | tissues with high or low expression of SPINT1 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
HPA Tissue Protein Expression Profiles | tissues with high or low expression of SPINT1 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of SPINT1 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
Hub Proteins Protein-Protein Interactions | interacting hub proteins for SPINT1 from the curated Hub Proteins Protein-Protein Interactions dataset. | |
HuGE Navigator Gene-Phenotype Associations | phenotypes associated with SPINT1 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
IMPC Knockout Mouse Phenotypes | phenotypes of mice caused by SPINT1 gene knockout from the IMPC Knockout Mouse Phenotypes dataset. | |
InterPro Predicted Protein Domain Annotations | protein domains predicted for SPINT1 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of SPINT1 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of SPINT1 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles | cell lines with high or low expression of SPINT1 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles dataset. | |
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles | cell lines with SPINT1 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset. | |
KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of SPINT1 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures | small molecule perturbations changing expression of SPINT1 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
LINCS L1000 CMAP CRISPR Knockout Consensus Signatures | gene perturbations changing expression of SPINT1 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset. | |
LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of SPINT1 gene from the LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
LOCATE Curated Protein Localization Annotations | cellular components containing SPINT1 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset. | |
LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain SPINT1 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by SPINT1 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of SPINT1 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
MPO Gene-Phenotype Associations | phenotypes of transgenic mice caused by SPINT1 gene mutations from the MPO Gene-Phenotype Associations dataset. | |
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations | gene perturbations changing expression of SPINT1 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset. | |
Pathway Commons Protein-Protein Interactions | interacting proteins for SPINT1 from the Pathway Commons Protein-Protein Interactions dataset. | |
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of SPINT1 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations | gene perturbations changing expression of SPINT1 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
PFOCR Pathway Figure Associations 2023 | pathways involving SPINT1 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
PFOCR Pathway Figure Associations 2024 | pathways involving SPINT1 protein from the Wikipathways PFOCR 2024 dataset. | |
Reactome Pathways 2024 | pathways involving SPINT1 protein from the Reactome Pathways 2024 dataset. | |
Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles | cell types and tissues with high or low DNA methylation of SPINT1 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset. | |
Roadmap Epigenomics Cell and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of SPINT1 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue Gene Expression Profiles dataset. | |
Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at SPINT1 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of SPINT1 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of SPINT1 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
Sanger Dependency Map Cancer Cell Line Proteomics | cell lines associated with SPINT1 protein from the Sanger Dependency Map Cancer Cell Line Proteomics dataset. | |
Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of SPINT1 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of SPINT1 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of SPINT1 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of SPINT1 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
TISSUES Curated Tissue Protein Expression Evidence Scores | tissues with high expression of SPINT1 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of SPINT1 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
TISSUES Experimental Tissue Protein Expression Evidence Scores | tissues with high expression of SPINT1 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset. | |
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of SPINT1 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with SPINT1 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with SPINT1 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
WikiPathways Pathways 2024 | pathways involving SPINT1 protein from the WikiPathways Pathways 2024 dataset. | |