Details for: LYPD6B

Gene ID: 130576

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: LYPD6B

Ensembl ID: ENSG00000150556

Description: LY6/PLAUR domain containing 6B

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • goblet cell CL0000160
    CSI 19.76
    rCSI 18.67%
    PRS 89.07
  • VIP GABAergic cortical interneuron CL4023016
    CSI 17.23
    rCSI 20.58%
    PRS 78.93
  • sncg GABAergic cortical interneuron CL4023015
    CSI 14.97
    rCSI 24.08%
    PRS 79.76
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 7.85
    rCSI 9.77%
    PRS 76.7
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 7.42
    rCSI 12.45%
    PRS 78.88
  • multi-ciliated epithelial cell CL0005012
    CSI 6.85
    rCSI 6.83%
    PRS 85.89
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 6.21
    rCSI 19.43%
    PRS 81.85
  • secretory cell CL0000151
    CSI 5.43
    rCSI 5.67%
    PRS 90.25
  • inhibitory interneuron CL0000498
    CSI 4.97
    rCSI 11.47%
    PRS 82.47
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 4.64
    rCSI 8.19%
    PRS 78.27
  • ciliated cell CL0000064
    CSI 4.36
    rCSI 7.06%
    PRS 85.68
  • dopaminergic neuron CL0000700
    CSI 3.81
    rCSI 21.52%
    PRS 81.05
  • nasal mucosa goblet cell CL0002480
    CSI 3.74
    rCSI 4.34%
    PRS 91.55
  • ependymal cell CL0000065
    CSI 3.62
    rCSI 7.34%
    PRS 74.34
  • keratinocyte CL0000312
    CSI 3.41
    rCSI 2.86%
    PRS 91.27
  • club cell CL0000158
    CSI 3.35
    rCSI 4.91%
    PRS 86.98
  • respiratory suprabasal cell CL4033048
    CSI 3.31
    rCSI 4.25%
    PRS 92.61
  • foveolar cell of stomach CL0002179
    CSI 3.3
    rCSI 7.02%
    PRS 92.99
  • fallopian tube secretory epithelial cell CL4030006
    CSI 3.18
    rCSI 3.06%
    PRS 89.7
  • respiratory basal cell CL0002633
    CSI 3.01
    rCSI 3.11%
    PRS 92.63
  • intrahepatic cholangiocyte CL0002538
    CSI 2.75
    rCSI 6.61%
    PRS 91.03
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 2.72
    rCSI 6.2%
    PRS 84.55
  • conjunctival epithelial cell CL1000432
    CSI 2.71
    rCSI 4.13%
    PRS 90.19
  • ciliated epithelial cell CL0000067
    CSI 2.59
    rCSI 2.27%
    PRS 82.87
  • BEST4+ enteroycte CL4030026
    CSI 2.5
    rCSI 3.11%
    PRS 90.83
  • glandular epithelial cell CL0000150
    CSI 2.41
    rCSI 6.35%
    PRS 96.43
  • stem cell CL0000034
    CSI 2.39
    rCSI 2.3%
    PRS 87.21
  • mucous neck cell CL0000651
    CSI 2.34
    rCSI 3.38%
    PRS 93.47
  • sst GABAergic cortical interneuron CL4023017
    CSI 2.25
    rCSI 2.9%
    PRS 79.94
  • kidney connecting tubule epithelial cell CL1000768
    CSI 2.23
    rCSI 5.66%
    PRS 85.29
  • pancreatic acinar cell CL0002064
    CSI 2.17
    rCSI 2.89%
    PRS 93.65
  • lung ciliated cell CL1000271
    CSI 2.1
    rCSI 2.43%
    PRS 85.93
  • tracheal goblet cell CL1000329
    CSI 2.07
    rCSI 4.52%
    PRS 93.33
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 2.06
    rCSI 5.34%
    PRS 88.57
  • retinal ganglion cell CL0000740
    CSI 2.06
    rCSI 4.54%
    PRS 81.22
  • renal principal cell CL0005009
    CSI 2.04
    rCSI 5.31%
    PRS 90.43
  • squamous epithelial cell CL0000076
    CSI 2.03
    rCSI 4.81%
    PRS 88.44
  • kidney epithelial cell CL0002518
    CSI 1.84
    rCSI 3.51%
    PRS 97.21
  • luminal epithelial cell of mammary gland CL0002326
    CSI 1.65
    rCSI 2.99%
    PRS 95.31
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 1.57
    rCSI 3.82%
    PRS 76.73
  • GABAergic neuron CL0000617
    CSI 1.52
    rCSI 5.08%
    PRS 78.43
  • corneal epithelial cell CL0000575
    CSI 1.35
    rCSI 3.87%
    PRS 92.65
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 1.33
    rCSI 3.19%
    PRS 81.34
  • pancreatic ductal cell CL0002079
    CSI 1.29
    rCSI 2.5%
    PRS 92.5
  • bronchial goblet cell CL1000312
    CSI 1.28
    rCSI 5.1%
    PRS 93.97
  • basal cell of epidermis CL0002187
    CSI 1.27
    rCSI 2.24%
    PRS 63.13
  • central nervous system neuron CL2000029
    CSI 1.13
    rCSI 8.27%
    PRS 83.37
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.03
    rCSI 1.25%
    PRS 72.55
  • deuterosomal cell CL4033044
    CSI 1.01
    rCSI 3.4%
    PRS 86.13
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.69
    rCSI 2.16%
    PRS 80.17
  • OFF midget ganglion cell CL4033047
    CSI 0.66
    rCSI 13.43%
    PRS 83.61
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.64
    rCSI 2.29%
    PRS 76.91
  • ON midget ganglion cell CL4033046
    CSI 0.34
    rCSI 6.99%
    PRS 82.98

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.

Comma-separated if multiple.
Comma-separated if multiple.
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)

Loading network (please wait)...

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 [LYPD6B](/details-gene/130576) (LY6/PLAUR domain containing 6B) is a protein-coding gene located on chromosome 2. It belongs to the Ly-6/uPAR (LU) superfamily of proteins, which are typically GPI-anchored to the cell membrane and involved in cell signaling and adhesion. Functionally, [LYPD6B](/details-gene/130576) is characterized as a modulator of nicotinic acetylcholine receptors ([Link](https://doi.org/10.1096/fj.15-274548), [Link](https://doi.org/10.3389/fcell.2021.662227)). Expression data shows its significance is exceptionally high in mucosal [goblet cells](/details-cell/CL0000160) and highly specific subsets of neurons, particularly various types of GABAergic interneurons, suggesting a dual role in both mucosal biology and the regulation of neuronal circuits. ## Cellular Roles and Expression Landscape The expression profile of [LYPD6B](/details-gene/130576) highlights its importance in two distinct cellular contexts: secretory epithelial cells and inhibitory neurons. **Overall**, the gene's most significant expression is observed in [goblet cell](/details-cell/CL0000160) (CSI: 19.76), a specialized intestinal epithelial cell responsible for mucus secretion. This is complemented by high significance scores in other secretory and ciliated cell types, including [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 6.85), [secretory cell](/details-cell/CL0000151) (CSI: 5.43), and [ciliated cell](/details-cell/CL0000064) (CSI: 4.36), suggesting a potential role in mucosal barrier function and physiology. In parallel, [LYPD6B](/details-gene/130576) demonstrates a highly specific and significant role within the central nervous system. It is a key marker for several subtypes of inhibitory neurons, with very high CSI values in [VIP GABAergic cortical interneuron](/details-cell/CL4023016) (CSI: 17.23), [sncg GABAergic cortical interneuron](/details-cell/CL4023015) (CSI: 14.97), and [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) (CSI: 7.85). Its presence in [dopaminergic neuron](/details-cell/CL0000700) (CSI: 3.81) further points to a specialized function in modulating neurotransmission. This specific expression pattern within inhibitory circuits is consistent with its known function as a regulator of the cholinergic system. ## Pathways and Molecular Function The known molecular function of [LYPD6B](/details-gene/130576) is primarily as a negative modulator of nicotinic acetylcholine receptors ([nAChRs](/details-gene/1134)), as supported by its annotation for '[acetylcholine receptor regulator activity](/details-go/GO:0030548)' and multiple studies ([Link](https://doi.org/10.1096/fj.15-274548), [Link](https://doi.org/10.3389/fcell.2021.662227)). It has been shown to specifically modulate heteromeric α3β4-containing nAChRs, but not α7 homomers, indicating a selective role in fine-tuning cholinergic signaling ([Link](https://doi.org/10.1096/fj.15-274548)). Its cellular localization is annotated to the '[extracellular region](/details-go/GO:0005576)' and the '[plasma membrane](/details-go/GO:0005886)', consistent with a protein that interacts with cell surface receptors. The Reactome pathway annotations, particularly '[Post-translational modification: synthesis of gpi-anchored proteins](/details-reactome/R-HSA-163125)', provide the mechanistic basis for its attachment to the outer leaflet of the plasma membrane, allowing it to interact with receptors and other extracellular molecules. ## Research Directions The dual, high-specificity expression pattern of [LYPD6B](/details-gene/130576) in both neuronal and mucosal tissues warrants further investigation into its context-dependent functions. **Proposed Hypotheses:** 1. Given its established role as a negative cholinergic modulator and its high expression in various GABAergic cortical interneurons, [LYPD6B](/details-gene/130576) likely functions as a critical homeostatic regulator, dampening excitatory cholinergic input onto inhibitory circuits to maintain the excitatory/inhibitory balance in the cortex. 2. The exceptionally high expression of [LYPD6B](/details-gene/130576) in [goblet cells](/details-cell/CL0000160) suggests a novel, non-neuronal function. It may modulate cholinergic-driven mucus secretion at mucosal surfaces, potentially acting as a brake on excessive secretion in response to parasympathetic stimulation. **Key Experimental Proposal:** To test the second hypothesis regarding its role in mucosal biology, an experiment using intestinal or airway organoids would be highly informative. CRISPR-Cas9 could be used to knock out [LYPD6B](/details-gene/130576) in these organoid cultures, which contain functional [goblet cells](/details-cell/CL0000160). The impact of the knockout on basal and acetylcholine-agonist (e.g., carbachol) stimulated mucus production could be quantified by measuring the expression of mucin genes (e.g., *MUC2*) via qPCR and assessing secreted mucin levels via ELISA. This would directly test whether [LYPD6B](/details-gene/130576) is a functional regulator of [goblet cell](/details-cell/CL0000160) activity. **Therapeutic Potential:** As a cell-surface, GPI-anchored protein that modulates a key neurotransmitter system, [LYPD6B](/details-gene/130576) presents a plausible therapeutic target. Its accessibility to extracellular agents makes it amenable to targeting with monoclonal antibodies or small molecule mimetics. In neurological conditions characterized by cholinergic hyperactivity, a therapeutic agent that mimics or enhances the inhibitory function of [LYPD6B](/details-gene/130576) could be beneficial. Conversely, in conditions of cholinergic hypoactivity, blocking its function could restore cholinergic tone. Its specific expression on certain interneuron subtypes might allow for more targeted neuromodulation compared to systemic cholinergic drugs.

Genular Protein ID: 4130810177

Symbol: LPD6B_HUMAN

Name: Ly6/PLAUR domain-containing protein 6B

UniProtKB Accession Codes:

Q8NI32 D3DP90 Q53TK0 Q7Z747 Q8IXK7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 3 ExpressionAtlas 1 GO 4 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 2 KEGG 1 MANE-Select 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 11 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

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: 26586467

Title: The prototoxin LYPD6B modulates heteromeric alpha3beta4-containing nicotinic acetylcholine receptors, but not alpha7 homomers.

PubMed ID: 26586467

DOI: 10.1096/fj.15-274548

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: 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: 183
  • Mass: 20656
  • Checksum: 817D3D181568C5A2
  • Sequence:
    • MLYKSSDRPA HKVSMLLLCH ALAIAVVQIV IFSESWAFAK NINFYNVRPP LDPTPFPNSF 
KCFTCENAGD NYNCNRWAED KWCPQNTQYC LTVHHFTSHG RSTSITKKCA SRSECHFVGC 
HHSRDSEHTE CRSCCEGMIC NVELPTNHTN AVFAVMHAQR TSGSSAPTLY LPVLAWVFVL 
PLL