| HGNC Family | Serine peptidase inhibitors, Kazal type (SPINK) |
| Name | serine peptidase inhibitor, Kazal type 9 |
| Description | The protein encoded by this gene is a Kazal-type serine protease inhibitor that appears to specifically target kallikrein-related peptidase 5 (KLK5) in the palmo-plantar epidermis. KLK5 is an important initiator of skin desquamation, so the encoded protease inhibitor may regulate skin differentiation in the palms of hands and soles of feet. This cationic protein has also been shown to promote keratinocyte migration by activation of the epidermal growth factor receptor (EGFR). [provided by RefSeq, Dec 2015] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSPINK9 is a Kazal‐type serine protease inhibitor that is predominantly expressed in the palmar–plantar epidermis, where its high local concentration appears to be essential for regulating skin desquamation. Both human studies have shown that SPINK9—also known as LEKTI‐2—is expressed at high levels in palmoplantar skin and is capable of selectively inhibiting kallikrein‐related peptidase 5 (KLK5), a protease that plays a central role in initiating proteolytic cascades critical to cornified cell shedding. In addition, expression analyses extending to other tissues and murine studies (which identified a potential orthologue, mSPINK12) indicate that similar protease regulation may be a conserved mechanism in epithelia that require a tightly controlled proteolytic environment."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDetailed biochemical analyses have revealed that SPINK9 exerts its inhibitory effect on KLK5 through a reactive loop comprising key residues (notably positions 48 and 49) that mediate a specific, pH‐dependent binding interaction. Substitutions within this loop strongly influence the inhibitor’s binding kinetics, particularly by altering the dissociation rate, and thereby refine both the potency and specificity of the inhibition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role as a protease inhibitor, SPINK9 is actively secreted by keratinocytes and has been found to trigger epidermal growth factor receptor (EGFR) transactivation via upregulation of ADAM metalloproteases—a process that also involves purinergic receptor signaling. This additional function promotes keratinocyte migration and may contribute to maintaining the physical and immunological barrier of the skin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maria Brattsand, Kristina Stefansson, Thomas Hubiche, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPINK9: a selective, skin-specific Kazal-type serine protease inhibitor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2008.448"}], "href": "https://doi.org/10.1038/jid.2008.448"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19194479"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19194479"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ulf Meyer-Hoffert, Zhihong Wu, Jens-Michael Schröder "}, {"type": "b", "children": [{"type": "t", "text": "Identification of lympho-epithelial Kazal-type inhibitor 2 in human skin as a kallikrein-related peptidase 5-specific protease inhibitor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0004372"}], "href": "https://doi.org/10.1371/journal.pone.0004372"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19190773"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19190773"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Karina Reiss, Ulf Meyer-Hoffert, Jan Fischer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and regulation of murine SPINK12, a potential orthologue of human LEKTI2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Dermatol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0625.2011.01355.x"}], "href": "https://doi.org/10.1111/j.1600-0625.2011.01355.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21899598"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21899598"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kristoffer Brännström, Anders Ohman, Ulrich von Pawel Rammingen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of SPINK9, a KLK5-specific inhibitor expressed in palmo-plantar epidermis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1515/hsz-2011-0238"}], "href": "https://doi.org/10.1515/hsz-2011-0238"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22505519"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22505519"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Maria Sperrhacke, Jan Fischer, Zhihong Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SPINK9 stimulates metalloprotease/EGFR-dependent keratinocyte migration via purinergic receptor activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2014.23"}], "href": "https://doi.org/10.1038/jid.2014.23"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24441102"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24441102"}]}]}]}
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| Synonyms | LEKTI2 |
| Proteins | ISK9_HUMAN |
| NCBI Gene ID | 643394 |
| 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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SPINK9 has 1,905 functional associations with biological entities spanning 8 categories (molecular profile, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 49 datasets.
Click the + buttons to view associations for SPINK9 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 SPINK9 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of SPINK9 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of SPINK9 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of SPINK9 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of SPINK9 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 SPINK9 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| CM4AI KOLF21J CRISPRi Gene Perturbation Atlas | gene perturbations changing expression of SPINK9 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing SPINK9 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with SPINK9 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 SPINK9 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 SPINK9 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by SPINK9 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with SPINK9 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with SPINK9 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 SPINK9 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at SPINK9 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 SPINK9 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of SPINK9 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with SPINK9 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving SPINK9 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing SPINK9 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by SPINK9 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2023 | molecular functions performed by SPINK9 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by SPINK9 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx eQTL 2025 | SNPs regulating expression of SPINK9 gene from the GTEx eQTL 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of SPINK9 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 SPINK9 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with SPINK9 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of SPINK9 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HPA Tissue Protein Expression Profiles | tissues with high or low expression of SPINK9 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for SPINK9 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of SPINK9 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Mouse Transcription Factor Targets 2025 | transcription factors regulating expression of SPINK9 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of SPINK9 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 SPINK9 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of SPINK9 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain SPINK9 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of SPINK9 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| Reactome Pathways 2024 | pathways involving SPINK9 protein from the Reactome Pathways 2024 dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of SPINK9 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of SPINK9 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of SPINK9 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of SPINK9 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 SPINK9 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 SPINK9 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of SPINK9 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of SPINK9 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 SPINK9 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 SPINK9 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
