Details for: LYPD6

Gene ID: 130574

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: LYPD6

Ensembl ID: ENSG00000187123

Description: LY6/PLAUR domain containing 6

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 12.85
    rCSI 21.56%
    PRS 94.94
  • VIP GABAergic cortical interneuron CL4023016
    CSI 10.45
    rCSI 12.48%
    PRS 94.72
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 6.72
    rCSI 11.87%
    PRS 94.69
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 6.48
    rCSI 8.06%
    PRS 93.78
  • sncg GABAergic cortical interneuron CL4023015
    CSI 6.46
    rCSI 10.39%
    PRS 94.72
  • mesothelial cell CL0000077
    CSI 6.3
    rCSI 24.64%
    PRS 93.12
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 6.16
    rCSI 7.11%
    PRS 95.72
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 5.24
    rCSI 16.38%
    PRS 95.41
  • neural progenitor cell CL0011020
    CSI 5.1
    rCSI 22.46%
    PRS 92.93
  • inhibitory interneuron CL0000498
    CSI 5.01
    rCSI 11.56%
    PRS 95.04
  • sst GABAergic cortical interneuron CL4023017
    CSI 4.79
    rCSI 6.18%
    PRS 95.28
  • cardiac neuron CL0010022
    CSI 4.67
    rCSI 14.95%
    PRS 97.91
  • retinal bipolar neuron CL0000748
    CSI 4.67
    rCSI 8.75%
    PRS 95.29
  • GABAergic amacrine cell CL4030027
    CSI 4.41
    rCSI 15.12%
    PRS 92.45
  • neural crest cell CL0011012
    CSI 3.82
    rCSI 3.02%
    PRS 97.09
  • Mueller cell CL0000636
    CSI 3.73
    rCSI 8.5%
    PRS 96.16
  • astrocyte of the cerebral cortex CL0002605
    CSI 3.62
    rCSI 8.11%
    PRS 94.75
  • Schwann cell CL0002573
    CSI 2.65
    rCSI 7.53%
    PRS 96.84
  • basal cell of epidermis CL0002187
    CSI 2.57
    rCSI 4.55%
    PRS 82.26
  • glioblast CL0000030
    CSI 2.46
    rCSI 3.93%
    PRS 95.62
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 1.61
    rCSI 13.88%
    PRS 96.12
  • retinal ganglion cell CL0000740
    CSI 1.17
    rCSI 2.58%
    PRS 94.48
  • GABAergic neuron CL0000617
    CSI 1.06
    rCSI 3.56%
    PRS 92.13
  • central nervous system neuron CL2000029
    CSI 0.54
    rCSI 3.98%
    PRS 95.4

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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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • 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 [LYPD6](/details-gene/130574) (LY6/PLAUR domain containing 6) is a protein-coding gene that belongs to the Ly-6/uPAR superfamily of cell surface proteins. Functionally, it is implicated in dual signaling roles, acting as a positive modulator of the canonical Wnt signaling pathway ([GO:0090263](https://www.ebi.ac.uk/QuickGO/term/GO:0090263)) and as a negative regulator of nicotinic acetylcholine receptors ([GO:0030550](https://www.ebi.ac.uk/QuickGO/term/GO:0030550)). Its expression profile shows remarkable specificity for the nervous system. **Overall**, it is a defining marker for numerous subtypes of inhibitory neurons, particularly [lamp5 GABAergic cortical interneurons](/details-cell/CL4023011) and [VIP GABAergic cortical interneurons](/details-cell/CL4023016), suggesting a critical role in regulating neuronal circuitry and synaptic transmission. ## Cellular Roles and Expression Landscape The expression pattern of [LYPD6](/details-gene/130574) firmly establishes it as a gene with a highly specialized function within the central nervous system. In the **Overall** context, it demonstrates pronounced significance in a diverse array of inhibitory neurons. It is the top marker for [lamp5 GABAergic cortical interneuron](/details-cell/CL4023011) (CSI: 12.85) and also shows high specificity in [VIP GABAergic cortical interneuron](/details-cell/CL4023016), [pvalb GABAergic cortical interneuron](/details-cell/CL4023018), and [sst GABAergic cortical interneuron](/details-cell/CL4023017). This widespread yet specific expression across functionally distinct interneuron classes suggests a fundamental role in shaping cortical inhibitory tone. Beyond mature interneurons, [LYPD6](/details-gene/130574) is also significantly expressed in progenitor and developing neural populations, including [caudal ganglionic eminence derived cortical interneuron](/details-cell/CL4023064), [neuroblast (sensu Nematoda and Protostomia)](/details-cell/CL0000338), and [neural progenitor cell](/details-cell/CL0011020). This expression pattern is consistent with its function in Wnt signaling, a pathway crucial for neurodevelopment. The gene's presence in other neuronal types such as [retinal bipolar neuron](/details-cell/CL0000748) and [cardiac neuron](/details-cell/CL0010022) further underscores its broad importance in neural tissues. An interesting exception to its near-exclusive neural expression is its significance in [mesothelial cells](/details-cell/CL0000077), which may indicate an uncharacterized role in serous membranes. ## Pathways and Molecular Function The molecular functions of [LYPD6](/details-gene/130574) are centered on the modulation of key signaling pathways at the cell surface. Its annotation for [positive regulation of canonical wnt signaling pathway](/details-cell/GO:0090263) is supported by structural studies showing it enhances Wnt signaling by binding to the Wnt coreceptor LRP6 ([Link](https://doi.org/10.1002/1873-3468.13212)). This function aligns with its expression in developing neural cells, where Wnt signaling is critical for proliferation and differentiation. Concurrently, [LYPD6](/details-gene/130574) functions as an [acetylcholine receptor inhibitor](/details-cell/GO:0030550), interacting with and modulating the activity of nicotinic acetylcholine receptors ([Link](https://doi.org/10.1111/jnc.13718)). This activity is highly relevant to its prominent expression in interneurons located at the [synapse](/details-cell/GO:0045202) and within [dendrites](/details-cell/GO:0030425), where it can fine-tune cholinergic neurotransmission and maintain network homeostasis ([Link](https://doi.org/10.3389/fcell.2021.662227)). The protein's localization to the [plasma membrane](/details-cell/GO:0005886) and [membrane rafts](/details-cell/GO:0045121) facilitates these interactions with cell-surface receptors and signaling complexes. ## Research Directions The dual functionality of [LYPD6](/details-gene/130574) as both a Wnt signaling enhancer and a cholinergic modulator, combined with its highly specific expression in inhibitory neurons, provides fertile ground for future investigation, particularly in the context of neurological disorders. One study has already suggested its involvement in Alzheimer's disease ([Link](https://doi.org/10.1016/j.neurobiolaging.2015.01.001)). Based on the available data, several testable hypotheses can be proposed: 1. Given its role as a negative modulator of nicotinic acetylcholine receptors, the age-related downregulation of [LYPD6](/details-gene/130574) in specific cortical interneuron populations could represent a compensatory mechanism to boost declining cholinergic signaling in early-stage neurodegenerative diseases. Conversely, its overexpression could exacerbate cholinergic deficits. 2. Based on its role in the Wnt pathway, aberrant expression of [LYPD6](/details-gene/130574) in [neural progenitor cells](/details-cell/CL0011020) during brain development or in adult neurogenic niches may lead to an imbalance in the generation of specific interneuron subtypes, contributing to neurodevelopmental disorders or epilepsy. A compelling experiment to investigate the first hypothesis could be designed. To test the role of [LYPD6](/details-gene/130574) in modulating cortical network activity in a disease context, one could utilize a mouse model of Alzheimer's disease and cross it with a line allowing for conditional deletion of [LYPD6](/details-gene/130574) specifically in [VIP GABAergic cortical interneurons](/details-cell/CL4023016). *In vivo* two-photon calcium imaging could then be employed to longitudinally track how the loss of [LYPD6](/details-gene/130574) in these neurons alters their activity and the surrounding network dynamics in response to cholinergic stimulation as pathology progresses. From a therapeutic perspective, [LYPD6](/details-gene/130574) is an intriguing target. Its localization on the cell surface makes it accessible to biologic drugs. Since it acts as an inhibitor of the cholinergic system, a therapeutic strategy involving **inhibition** of [LYPD6](/details-gene/130574) function—perhaps via a blocking antibody or a small molecule—could be explored to enhance cholinergic neurotransmission in diseases characterized by cholinergic decline, such as Alzheimer's disease. Its high neuronal specificity suggests such an approach may offer a more targeted intervention with a better side-effect profile than current systemic cholinergic agents.

Genular Protein ID: 1274950527

Symbol: LYPD6_HUMAN

Name: Ly6/PLAUR domain-containing protein 6

UniProtKB Accession Codes:

Q86Y78 B3KWC0 Q4G121 Q53TR3 Q659B1

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 5 ExpressionAtlas 1 GO 10 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 2 PDBsum 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 19653121

Title: Identification and characterization of human LYPD6, a new member of the Ly-6 superfamily.

PubMed ID: 19653121

DOI: 10.1007/s11033-009-9663-7

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: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 15340161

Title: Signal peptide prediction based on analysis of experimentally verified cleavage sites.

PubMed ID: 15340161

DOI: 10.1110/ps.04682504

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 25680266

Title: Prostate stem cell antigen interacts with nicotinic acetylcholine receptors and is affected in Alzheimer's disease.

PubMed ID: 25680266

DOI: 10.1016/j.neurobiolaging.2015.01.001

PubMed ID: 27344019

Title: Functional interaction between Lypd6 and nicotinic acetylcholine receptors.

PubMed ID: 27344019

DOI: 10.1111/jnc.13718

PubMed ID: 34631692

Title: Human Three-Finger protein Lypd6 is a negative modulator of the cholinergic System in the brain.

PubMed ID: 34631692

DOI: 10.3389/fcell.2021.662227

PubMed ID: 30069874

Title: Structure of the Wnt signaling enhancer LYPD6 and its interactions with the Wnt coreceptor LRP6.

PubMed ID: 30069874

DOI: 10.1002/1873-3468.13212

PubMed ID: 33019770

Title: Structural Diversity and Dynamics of Human Three-Finger Proteins Acting on Nicotinic Acetylcholine Receptors.

PubMed ID: 33019770

DOI: 10.3390/ijms21197280

Sequence Information:

  • Length: 171
  • Mass: 19118
  • Checksum: 1BAEEE9CD18F5470
  • Sequence:
    • MEPGPALAWL LLLSLLADCL KAAQSRDFTV KDIIYLHPST TPYPGGFKCF TCEKAADNYE 
CNRWAPDIYC PRETRYCYTQ HTMEVTGNSI SVTKRCVPLE ECLSTGCRDS EHEGHKVCTS 
CCEGNICNLP LPRNETDATF ATTSPINQTN GHPRCMSVIV SCLWLWLGLM L