1. Gene Aliases

CDH17, HPT-1, Intestinal Peptide-Associated Transporter HPT-1, Cadherin 17, LI Cadherin (Liver-Intestine), Liver-Intestine Cadherin, Cadherin-17, Human Intestinal Peptide-Associated Transporter HPT-1, Human Peptide Transporter 1, HPT-1 Cadherin, LI Cadherin, Cadherin-16, LI-Cadherin, Cadherin, CADHERIN, CDH16, HPT1

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=CDH17&keywords=Cdh17].

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

B cell differentiation [The process in which a precursor cell type acquires the specialized features of a B cell. A B cell is a lymphocyte of B lineage with the phenotype CD19-positive and capable of B cell mediated immunity.|Note that immunologists typically use the word 'development' to refer to cells of B or T cell lineages undergoing the process that GO describes as 'cell differentiation'. GO:0030183]

T cell mediated immunity [Any process involved in the carrying out of an immune response by a T cell. GO:0002456]

adherens junction organization [A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of an adherens junction. An adherens junction is a cell-cell junction composed of the epithelial cadherin-catenin complex at which the cytoplasmic face of the plasma membrane is attached to actin filaments. GO:0034332]

calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules [The attachment of one cell to another cell via adhesion molecules that require the presence of calcium for the interaction. GO:0016339]

cell morphogenesis [The developmental process in which the size or shape of a cell is generated and organized. GO:0000902]

cell-cell adhesion mediated by cadherin [The attachment of one cell to another cell via a cadherin, transmembrane proteins having repeating extracellular calcium ion binding domains. GO:0044331]

cell-cell junction assembly [The aggregation, arrangement and bonding together of a set of components to form a junction between cells. GO:0007043]

germinal center B cell differentiation [The process in which a B cell in the spleen acquires the specialized features of a germinal center B cell. Germinal center B cells are rapidly cycling B cells which have downregulated IgD expression and exhibit high levels of binding by peanut agglutinin (PNA).|Note that immunologists typically use the word 'development' to refer to cells of B or T cell lineages undergoing the process that GO describes as 'cell differentiation'. GO:0002314]

homophilic cell adhesion via plasma membrane adhesion molecules [The attachment of a plasma membrane adhesion molecule in one cell to an identical molecule in an adjacent cell. GO:0007156]

integrin-mediated signaling pathway [The series of molecular signals initiated by an extracellular ligand binding to an integrin on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription. GO:0007229]

marginal zone B cell differentiation [The process in which a B cell in the spleen acquires the specialized features of a marginal zone B cell. Marginal zone B cells are localized in a distinct anatomical region of the spleen that represents the major antigen-filtering and scavenging area (by specialized macrophages resident there). It appears that they are preselected to express a BCR repertoire similar to B-1 B cells, biased toward bacterial cell wall constituents and senescent self-components (such as oxidized LDL).|Note that immunologists typically use the word 'development' to refer to cells of B or T cell lineages undergoing the process that GO describes as 'cell differentiation'. GO:0002315]

oligopeptide transmembrane transport [The process in which an oligopeptide is transported across a membrane. Oligopeptides are molecules that contain a small number (2 to 20) of amino-acid residues connected by peptide linkages.|Note that this term is not intended for use in annotating lateral movement within membranes. GO:0035672]

oligopeptide transport [The directed movement of oligopeptides into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. Oligopeptides are molecules that contain a small number (2 to 20) of amino-acid residues connected by peptide linkages. GO:0006857]

positive regulation of integrin activation by cell surface receptor linked signal transduction [Any process that activates or increases the frequency, rate, or extent of integrin activation by cell surface receptor linked signal transduction. This can occur by increased affinity of an integrin for its extracellular ligands. GO:0033626]

spleen development [The process whose specific outcome is the progression of the spleen over time, from its formation to the mature structure. The spleen is a large vascular lymphatic organ composed of white and red pulp, involved both in hemopoietic and immune system functions. GO:0048536]

MSigDB Signatures:

WP_PLEURAL_MESOTHELIOMA: Pleural mesothelioma [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_PLEURAL_MESOTHELIOMA.html]

REACTOME_CELL_CELL_COMMUNICATION: Cell-Cell communication [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CELL_CELL_COMMUNICATION.html]

REACTOME_CELL_JUNCTION_ORGANIZATION: Cell junction organization [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CELL_JUNCTION_ORGANIZATION.html]

REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS: Adherens junctions interactions [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS.html]

REACTOME_CELL_CELL_JUNCTION_ORGANIZATION: Cell-cell junction organization [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_CELL_CELL_JUNCTION_ORGANIZATION.html]

WP_PANCREATIC_CANCER_SUBTYPES: Pancreatic cancer subtypes [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_PANCREATIC_CANCER_SUBTYPES.html]

7. Gene Descriptions

NCBI Gene Summary: This gene is a member of the cadherin superfamily, genes encoding calcium-dependent, membrane-associated glycoproteins. The encoded protein is cadherin-like, consisting of an extracellular region, containing 7 cadherin domains, and a transmembrane region but lacking the conserved cytoplasmic domain. The protein is a component of the gastrointestinal tract and pancreatic ducts, acting as an intestinal proton-dependent peptide transporter in the first step in oral absorption of many medically important peptide-based drugs. The protein may also play a role in the morphological organization of liver and intestine. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

GeneCards Summary: CDH17 (Cadherin 17) is a Protein Coding gene. Diseases associated with CDH17 include Ectodermal Dysplasia, Ectrodactyly, And Macular Dystrophy Syndrome and Elsahy-Waters Syndrome. Among its related pathways are Regulation of CDH11 Expression and Function and ERK Signaling. Gene Ontology (GO) annotations related to this gene include calcium ion binding and proton-dependent oligopeptide secondary active transmembrane transporter activity. An important paralog of this gene is CDH23.

UniProtKB/Swiss-Prot Summary: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. LI-cadherin may have a role in the morphological organization of liver and intestine. Involved in intestinal peptide transport.

8. Cellular Location of Gene Product

Distinct membranous and cytoplasmic expression in gastrointestinal glands. Mainly localized to the cell junctions. In addition localized to the nucleoplasm. Predicted location: Membrane, Intracellular (different isoforms) [https://www.proteinatlas.org/ENSG00000079112/subcellular]

9. Mechanistic Information

Summary

Cdh17, involved in cell adhesion and intestinal peptide transport, becomes dysregulated in liver diseases and toxicities [CS: 8]. In the context of acute acetaminophen (APAP) intoxication, a known liver toxicant, hepatocytes at the regenerating front upregulate Cdh17 [CS: 7]. This upregulation aids in the reprogramming of these cells to a pericentral state, essential for liver regeneration [CS: 6]. The increase in Cdh17 expression likely facilitates the re-establishment of cell adhesion and tissue structure, crucial for repairing liver damage induced by APAP [CS: 7].

In hepatocellular carcinoma (HCC), an alternative mRNA splicing isoform of CDH17 with a skipped exon 7 results in an open reading frame shift [CS: 8]. This abnormal isoform is associated with a shorter survival time, indicating a detrimental effect [CS: 7]. The normal function of CDH17 in cell adhesion and signaling pathways, such as the Wnt/beta-catenin pathway, is crucial for maintaining liver tissue organization and function [CS: 9]. In HCC, the aberrant CDH17 isoform disrupts these pathways, leading to uncontrolled cell proliferation and impaired cell adhesion, contributing to tumor progression and poor prognosis [CS: 8].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: intestine (tissue enriched) [https://www.proteinatlas.org/ENSG00000079112/tissue]

Cell type enchanced: distal enterocytes, enteroendocrine cells, intestinal goblet cells, paneth cells, proximal enterocytes, undifferentiated cells (group enriched) [https://www.proteinatlas.org/ENSG00000079112/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: