Details for: LYPD8

Gene ID: 646627

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: LYPD8

Ensembl ID: ENSG00000259823

Description: LY6/PLAUR domain containing 8

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 10.24
    rCSI 24.9%
    PRS 98.74
  • enteroendocrine cell CL0000164
    CSI 5.06
    rCSI 6.91%
    PRS 99.36
  • intestine goblet cell CL0019031
    CSI 4.46
    rCSI 3.96%
    PRS 99.62
  • colon epithelial cell CL0011108
    CSI 3.69
    rCSI 3.87%
    PRS 99.77
  • BEST4+ enteroycte CL4030026
    CSI 3.45
    rCSI 4.29%
    PRS 99.5
  • enteroendocrine cell of colon CL0009042
    CSI 3.03
    rCSI 14.2%
    PRS 99.67
  • colon goblet cell CL0009039
    CSI 2.47
    rCSI 5.88%
    PRS 99.77
  • enterocyte CL0000584
    CSI 2.35
    rCSI 3.79%
    PRS 99.54
  • enterocyte of epithelium of large intestine CL0002071
    CSI 1.15
    rCSI 6.01%
    PRS 99.79
  • paneth cell of colon CL0009009
    CSI 0.62
    rCSI 6.14%
    PRS 99.79

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [LYPD8](/details-gene/646627) (LY6/PLAUR domain containing 8) is a protein-coding gene located on chromosome 1q44. It encodes a GPI-anchored protein that is a member of the Ly6/PLAUR superfamily. Functionally, [LYPD8](/details-gene/646627) plays a critical role in innate mucosal immunity within the gastrointestinal tract. It is highly expressed by various colonic epithelial cell types and is secreted into the gut lumen, where it functions to segregate flagellated bacteria from the epithelial surface, thereby maintaining intestinal homeostasis and preventing inflammation ([Link](https://doi.org/10.1038/nature17406)). This function is consistent with its annotation in the defense response against gram-negative bacteria. ## Cellular Roles and Expression Landscape The expression profile of [LYPD8](/details-gene/646627) highlights its specialized role in the intestinal epithelium. **Overall**, it shows high significance scores in multiple cell types critical to colon function, including [intestine goblet cells](/details-cell/CL0019031) (CSI: 4.46), [colon epithelial cells](/details-cell/CL0011108) (CSI: 3.69), [enterocytes](/details-cell/CL0000584) (CSI: 2.35), and [enteroendocrine cells](/details-cell/CL0000164) (CSI: 5.06). This broad expression across the colonic epithelium suggests its function is integral to the general barrier and defense mechanisms of the large intestine. Intriguingly, the highest significance score is observed in [L2/3-6 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4023040) (CSI: 10.24). While the primary characterized function of [LYPD8](/details-gene/646627) relates to gut immunity, this strong neuronal signal suggests a potential, yet uncharacterized, role in the central nervous system. ## Pathways and Molecular Function The molecular function of [LYPD8](/details-gene/646627) is closely tied to its identity as a GPI-anchored protein, a process detailed in the Reactome pathway for 'Post-translational modification: synthesis of gpi-anchored proteins' ([R-HSA-163125](https://reactome.org/content/detail/R-HSA-163125)). This modification anchors it to the outer leaflet of the plasma membrane, as indicated by Gene Ontology components like 'Plasma membrane' ([GO:0005886](https://www.ebi.ac.uk/QuickGO/term/GO:0005886)) and 'Side of membrane' ([GO:0098552](https://www.ebi.ac.uk/QuickGO/term/GO:0098552)). Once expressed on the cell surface of colonic epithelial cells, [LYPD8](/details-gene/646627) is shed into the intestinal lumen. Its primary biological process, 'Defense response to gram-negative bacterium' ([GO:0050829](https://www.ebi.ac.uk/QuickGO/term/GO:0050829)), is executed in the 'Extracellular space' ([GO:0005615](https://www.ebi.ac.uk/QuickGO/term/GO:0005615)). Research indicates it specifically binds to bacterial flagellin, which limits the motility of flagellated bacteria and prevents them from penetrating the inner mucus layer and approaching the epithelium ([Link](https://doi.org/10.1038/nature17406)). ## Research Directions The specific function of [LYPD8](/details-gene/646627) in maintaining the gut epithelial barrier opens several avenues for future research, particularly concerning inflammatory diseases and host-microbe interactions. **Proposed Hypotheses:** 1. Reduced expression or loss-of-function variants of [LYPD8](/details-gene/646627) may represent a genetic susceptibility factor for inflammatory bowel disease (IBD) by compromising the segregation of pro-inflammatory microbes from the gut wall. 2. Given its high significance in [L2/3-6 intratelencephalic projecting glutamatergic neurons](/details-cell/CL4023040), [LYPD8](/details-gene/646627) may play a role in neuronal cell adhesion, synaptic organization, or signaling within the cerebral cortex, a function completely distinct from its role in the gut. 3. The expression of [LYPD8](/details-gene/646627) in the colon may be dynamically regulated by the composition of the gut microbiome, with increased abundance of flagellated bacteria inducing higher [LYPD8](/details-gene/646627) transcription as a host-adaptive defensive response. **Key Experimental Approach:** To test the hypothesis linking [LYPD8](/details-gene/646627) to IBD susceptibility (Hypothesis 1), one could generate intestinal organoids from IBD patient-derived induced pluripotent stem cells (iPSCs) harboring putative risk variants in the [LYPD8](/details-gene/646627) gene and compare them to organoids from healthy controls. Barrier function could be assessed by measuring transepithelial electrical resistance (TEER). Following a challenge with live, flagellated *E. coli*, one could quantify bacterial translocation and the secretion of pro-inflammatory cytokines (e.g., IL-8, TNF-alpha) via ELISA to determine if [LYPD8](/details-gene/646627) dysfunction leads to a heightened inflammatory response. **Therapeutic Potential:** As [LYPD8](/details-gene/646627) has a protective role in the gut, it represents a potential therapeutic agent rather than a target for inhibition. Strategies could focus on its **activation** or supplementation. Development of small molecules that enhance [LYPD8](/details-gene/646627) expression or stability could be a novel, non-immunosuppressive approach to treating IBD or other conditions characterized by a compromised gut barrier. Alternatively, recombinant [LYPD8](/details-gene/646627) protein could be explored as a locally administered biologic to reinforce mucosal defense.

Genular Protein ID: 3081872731

Symbol: LYPD8_HUMAN

Name: N/A

UniProtKB Accession Codes:

Q6UX82 A0A075B722 K7ELG6

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 1 GO 5 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 InterPro 2 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 1 RefSeq 2 STRING 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12975309

Title: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

PubMed ID: 12975309

DOI: 10.1101/gr.1293003

PubMed ID: 16710414

Title: The DNA sequence and biological annotation of human chromosome 1.

PubMed ID: 16710414

DOI: 10.1038/nature04727

PubMed ID: 27027293

Title: Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia.

PubMed ID: 27027293

DOI: 10.1038/nature17406

Sequence Information:

  • Length: 237
  • Mass: 25265
  • Checksum: AB3EFE9E31274A3A
  • Sequence:
    • MKGILVAGIT AVLVAAVESL SCVQCNSWEK SCVNSIASEC PSHANTSCIS SSASSSLETP 
VRLYQNMFCS AENCSEETHI TAFTVHVSAE EHFHFVSQCC QGKECSNTSD ALDPPLKNVS 
SNAECPACYE SNGTSCHGKP WKCYEEEQCV FLVAELKNDI ESKSLVLKGC SNVSNATCQF 
LSGENKTLGG VIFRKFECAN VNSLTPTSAP TTSHNVGSKA SLYLLALASL LLRGLLP