| HGNC Family | Serine peptidase inhibitors, Kazal type (SPINK) |
| Name | serine peptidase inhibitor, Kazal type 4 |
| Description | Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Mar 2025] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSPINK4, a serine protease inhibitor of the Kazal type, is predominantly expressed in the gastrointestinal tract, especially by goblet cells. In celiac disease, SPINK4 expression is markedly elevated in untreated patients and drops sharply with a gluten‐free diet, suggesting that its regulation is closely linked with changes in goblet cell activity rather than contributing to genetic susceptibility. Its abundance in goblet cells also underlines its important role as a gastrointestinal peptide."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of colorectal cancer (CRC), SPINK4 appears to act as a tumor suppressor. Downregulation of SPINK4 in CRC correlates with poor patient prognosis, while experimental overexpression of SPINK4 in CRC cells reduces proliferation, invasion, and migration, in addition to modulating glycolytic activity and enhancing apoptotic pathways. These findings suggest that SPINK4 plays a key role in controlling cell metabolism and tumor progression, positioning it as a promising target for metabolic intervention in cancer therapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Martin C Wapenaar, Alienke J Monsuur, Jos Poell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The SPINK gene family and celiac disease susceptibility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunogenetics (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00251-007-0199-5"}], "href": "https://doi.org/10.1007/s00251-007-0199-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17333166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17333166"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xiaojie Wang, Qian Yu, Waleed M Ghareeb, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulated SPINK4 is associated with poor survival in colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12885-019-6484-5"}], "href": "https://doi.org/10.1186/s12885-019-6484-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31888570"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31888570"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xiaodi Yang, Sen Jiang, Zhen Yuan, et al. "}, {"type": "b", "children": [{"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SPINK4 "}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": "modulates inhibition of glycolysis against colorectal cancer progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomol Biomed (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.17305/bb.2024.10338"}], "href": "https://doi.org/10.17305/bb.2024.10338"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38747892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38747892"}]}]}]}
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| Synonyms | PEC60, PEC-60, HEL136 |
| Proteins | ISK4_HUMAN |
| NCBI Gene ID | 27290 |
| 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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SPINK4 has 4,177 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 86 datasets.
Click the + buttons to view associations for SPINK4 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Achilles Cell Line Gene Essentiality Profiles | cell lines with fitness changed by SPINK4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset. | |
| Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of SPINK4 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of SPINK4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of SPINK4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Cell Line Gene Expression Profiles | cell lines with high or low expression of SPINK4 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 SPINK4 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 SPINK4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset. | |
| Carcinogenome Chemical Perturbation Carcinogenicity Signatures | small molecule perturbations changing expression of SPINK4 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of SPINK4 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 SPINK4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| CellMarker Gene-Cell Type Associations | cell types associated with SPINK4 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 SPINK4 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of SPINK4 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 SPINK4 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 SPINK4 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of SPINK4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing SPINK4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 | cellular components containing SPINK4 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 SPINK4 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 SPINK4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of SPINK4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with SPINK4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| CTD Gene-Chemical Interactions | chemicals interacting with SPINK4 gene/protein from the curated CTD Gene-Chemical Interactions dataset. | |
| CTD Gene-Disease Associations | diseases associated with SPINK4 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by SPINK4 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 SPINK4 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 SPINK4 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 SPINK4 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 SPINK4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with SPINK4 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 SPINK4 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 SPINK4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of SPINK4 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 SPINK4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
| GAD High Level Gene-Disease Associations | diseases associated with SPINK4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset. | |
| GDSC Cell Line Gene Expression Profiles | cell lines with high or low expression of SPINK4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing SPINK4 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of SPINK4 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 SPINK4 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 SPINK4 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 SPINK4 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 SPINK4 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 SPINK4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving SPINK4 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing SPINK4 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by SPINK4 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GTEx eQTL 2025 | SNPs regulating expression of SPINK4 gene from the GTEx eQTL 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of SPINK4 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 SPINK4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with SPINK4 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 SPINK4 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of SPINK4 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 SPINK4 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with SPINK4 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for SPINK4 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of SPINK4 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 SPINK4 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 SPINK4 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 SPINK4 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 SPINK4 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 SPINK4 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
| LINCS L1000 CMAP CRISPR Knockout Consensus Signatures | gene perturbations changing expression of SPINK4 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 SPINK4 gene from the LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| LOCATE Curated Protein Localization Annotations | cellular components containing SPINK4 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 SPINK4 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of SPINK4 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| MoTrPAC Rat Endurance Exercise Training | tissue samples with high or low expression of SPINK4 gene relative to other tissue samples from the MoTrPAC Rat Endurance Exercise Training dataset. | |
| MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations | gene perturbations changing expression of SPINK4 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset. | |
| NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles | drug perturbations changing expression of SPINK4 gene from the NIBR DRUG-seq U2OS MoA Box dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of SPINK4 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 SPINK4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving SPINK4 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving SPINK4 protein from the Wikipathways PFOCR 2024 dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at SPINK4 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of SPINK4 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of SPINK4 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of SPINK4 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of SPINK4 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
| TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of SPINK4 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of SPINK4 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 SPINK4 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores | tissues with high expression of SPINK4 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 SPINK4 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 SPINK4 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 SPINK4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
| WikiPathways Pathways 2024 | pathways involving SPINK4 protein from the WikiPathways Pathways 2024 dataset. | |
