Details for: GPC5

Gene ID: 2262

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: GPC5

Ensembl ID: ENSG00000179399

Description: glypican 5

Cell Significance Landscape

Associated with

Significant Cells

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

  • astrocyte CL0000127
    CSI 32.59
    rCSI 69.44%
    PRS 68
  • astrocyte of the cerebral cortex CL0002605
    CSI 30.67
    rCSI 68.76%
    PRS 76.96
  • vascular leptomeningeal cell CL4023051
    CSI 28.15
    rCSI 49.35%
    PRS 86.17
  • Bergmann glial cell CL0000644
    CSI 23.29
    rCSI 31.87%
    PRS 82.26
  • Schwann cell CL0002573
    CSI 16.22
    rCSI 46.12%
    PRS 86.4
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 15.95
    rCSI 19.84%
    PRS 74.37
  • kidney connecting tubule epithelial cell CL1000768
    CSI 14.8
    rCSI 37.54%
    PRS 83.37
  • neural cell CL0002319
    CSI 14.56
    rCSI 54.95%
    PRS 74.55
  • GABAergic amacrine cell CL4030027
    CSI 13.88
    rCSI 47.54%
    PRS 77.23
  • adipocyte CL0000136
    CSI 13.02
    rCSI 16.72%
    PRS 81.64
  • rod bipolar cell CL0000751
    CSI 12.16
    rCSI 21.85%
    PRS 84.77
  • cerebral cortex endothelial cell CL1001602
    CSI 11.65
    rCSI 20.15%
    PRS 84.32
  • interneuron CL0000099
    CSI 11.56
    rCSI 23.21%
    PRS 83.56
  • L2/3 intratelencephalic projecting glutamatergic neuron CL4030059
    CSI 11.03
    rCSI 23.93%
    PRS 78.61
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 10.82
    rCSI 27.98%
    PRS 86.77
  • chondrocyte CL0000138
    CSI 10.49
    rCSI 16.69%
    PRS 85.04
  • VIP GABAergic cortical interneuron CL4023016
    CSI 10.4
    rCSI 12.43%
    PRS 76.54
  • renal interstitial pericyte CL1001318
    CSI 10.36
    rCSI 28.54%
    PRS 86.97
  • inhibitory interneuron CL0000498
    CSI 9.81
    rCSI 22.65%
    PRS 80.56
  • mature astrocyte CL0002627
    CSI 9.79
    rCSI 41.62%
    PRS 82.9
  • cerebellar granule cell CL0001031
    CSI 9.16
    rCSI 13.47%
    PRS 84.52
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 8.49
    rCSI 14.25%
    PRS 76.47
  • endocardial cell CL0002350
    CSI 8.28
    rCSI 39.62%
    PRS 86.11
  • sncg GABAergic cortical interneuron CL4023015
    CSI 8.24
    rCSI 13.25%
    PRS 77.5
  • pulmonary alveolar type 2 cell CL0002063
    CSI 7.78
    rCSI 12.06%
    PRS 90.99
  • retina horizontal cell CL0000745
    CSI 7.66
    rCSI 11.68%
    PRS 86.67
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 7.47
    rCSI 19.48%
    PRS 91.22
  • central nervous system neuron CL2000029
    CSI 7.34
    rCSI 53.92%
    PRS 81.13
  • amacrine cell CL0000561
    CSI 7.26
    rCSI 21.04%
    PRS 81.24
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 7.23
    rCSI 17.58%
    PRS 74.26
  • S cone cell CL0003050
    CSI 7.1
    rCSI 31.2%
    PRS 85.21
  • cardiac muscle cell CL0000746
    CSI 7.03
    rCSI 10.08%
    PRS 81.92
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 6.78
    rCSI 25.62%
    PRS 76.73
  • regular atrial cardiac myocyte CL0002129
    CSI 6.77
    rCSI 21.79%
    PRS 86.41
  • retinal ganglion cell CL0000740
    CSI 6.75
    rCSI 14.92%
    PRS 79.04
  • mononuclear phagocyte CL0000113
    CSI 6.65
    rCSI 14.64%
    PRS 92.19
  • pulmonary alveolar type 1 cell CL0002062
    CSI 6.56
    rCSI 37.82%
    PRS 86.69
  • medium spiny neuron CL1001474
    CSI 6.53
    rCSI 56.27%
    PRS 81.46
  • hepatic stellate cell CL0000632
    CSI 6.51
    rCSI 24.39%
    PRS 84.95
  • sst GABAergic cortical interneuron CL4023017
    CSI 6.17
    rCSI 7.96%
    PRS 77.63
  • L6b glutamatergic cortical neuron CL4023038
    CSI 5.82
    rCSI 18.19%
    PRS 77.88
  • epithelial cell of proximal tubule CL0002306
    CSI 5.55
    rCSI 13.55%
    PRS 83.15
  • glycinergic amacrine cell CL4030028
    CSI 5.47
    rCSI 14.25%
    PRS 84.04
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 5.31
    rCSI 16.61%
    PRS 79.57
  • glial cell CL0000125
    CSI 5.06
    rCSI 19.27%
    PRS 83.21
  • glioblast CL0000030
    CSI 5.03
    rCSI 8.02%
    PRS 82.41
  • neural crest cell CL0011012
    CSI 4.94
    rCSI 3.9%
    PRS 82.63
  • endothelial cell of placenta CL0009092
    CSI 4.8
    rCSI 23.67%
    PRS 93.73
  • ependymal cell CL0000065
    CSI 4.78
    rCSI 9.7%
    PRS 71.92
  • serotonergic neuron CL0000850
    CSI 4.78
    rCSI 21.34%
    PRS 75.44
  • L4 intratelencephalic projecting glutamatergic neuron CL4030063
    CSI 4.78
    rCSI 11.42%
    PRS 79.2
  • H2 horizontal cell CL0004218
    CSI 4.7
    rCSI 23.38%
    PRS 84.3
  • renal principal cell CL0005009
    CSI 4.69
    rCSI 12.19%
    PRS 89.1
  • macroglial cell CL0000126
    CSI 4.65
    rCSI 11.95%
    PRS 86.05
  • glutamatergic neuron CL0000679
    CSI 4.23
    rCSI 8.7%
    PRS 78.19
  • dopaminergic neuron CL0000700
    CSI 4.23
    rCSI 23.88%
    PRS 79.05
  • L5/6 near-projecting glutamatergic neuron CL4030067
    CSI 4.21
    rCSI 13.82%
    PRS 78.13
  • kidney collecting duct intercalated cell CL1001432
    CSI 4.1
    rCSI 29.29%
    PRS 85.88
  • lung secretory cell CL1000272
    CSI 3.3
    rCSI 8.17%
    PRS 90.33
  • GABAergic neuron CL0000617
    CSI 3.11
    rCSI 10.43%
    PRS 76.28
  • OFFx cell CL4033036
    CSI 3.09
    rCSI 14.54%
    PRS 80.91
  • brain vascular cell CL4023072
    CSI 3.03
    rCSI 31.35%
    PRS 84.14
  • podocyte CL0000653
    CSI 2.99
    rCSI 13.29%
    PRS 90.4
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.98
    rCSI 4.22%
    PRS 87.47
  • H1 horizontal cell CL0004217
    CSI 2.93
    rCSI 11.59%
    PRS 83.77
  • parietal epithelial cell CL1000452
    CSI 2.89
    rCSI 7.71%
    PRS 84.21
  • lung neuroendocrine cell CL1000223
    CSI 2.63
    rCSI 3.89%
    PRS 91.6
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 2.62
    rCSI 27.73%
    PRS 85.96
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 2.59
    rCSI 22.34%
    PRS 84.48
  • renal beta-intercalated cell CL0002201
    CSI 2.57
    rCSI 6.14%
    PRS 89.76
  • ON parasol ganglion cell CL4033052
    CSI 2.55
    rCSI 36.25%
    PRS 82.25
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.51
    rCSI 1.95%
    PRS 92.38
  • regular ventricular cardiac myocyte CL0002131
    CSI 2.35
    rCSI 14.66%
    PRS 83.51
  • direct pathway medium spiny neuron CL4023026
    CSI 2.29
    rCSI 54.85%
    PRS 74.1
  • indirect pathway medium spiny neuron CL4023029
    CSI 2.27
    rCSI 54.67%
    PRS 74.29
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 2.03
    rCSI 3.58%
    PRS 75.95
  • ON midget ganglion cell CL4033046
    CSI 1.91
    rCSI 38.96%
    PRS 81.14
  • macula densa epithelial cell CL1000850
    CSI 1.86
    rCSI 26.72%
    PRS 87.83
  • mesangial cell CL0000650
    CSI 1.81
    rCSI 7.37%
    PRS 94.77
  • neural progenitor cell CL0011020
    CSI 1.72
    rCSI 7.57%
    PRS 79.36
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 1.6
    rCSI 2.92%
    PRS 83.44
  • retinal cone cell CL0000573
    CSI 1.6
    rCSI 2.57%
    PRS 82.1
  • corticothalamic-projecting glutamatergic cortical neuron CL4023013
    CSI 1.24
    rCSI 7.33%
    PRS 76.98
  • OFF midget ganglion cell CL4033047
    CSI 1.02
    rCSI 20.71%
    PRS 81.93
  • diffuse bipolar 3a cell CL4033029
    CSI 0.78
    rCSI 5.33%
    PRS 82.15
  • blood vessel smooth muscle cell CL0019018
    CSI 0.73
    rCSI 5.93%
    PRS 86.73
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.59
    rCSI 2.14%
    PRS 74.38

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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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)

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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 [GPC5](/details-gene/2262) (glypican 5) is a member of the glypican family of heparan sulfate proteoglycans that are attached to the cell surface via a glycosylphosphatidylinositol (GPI) anchor. It plays a crucial role in cell signaling by binding to and modulating the activity of various growth factors and morphogens. Functionally, [GPC5](/details-gene/2262) is involved in key developmental processes, including the regulation of the Wnt and Hedgehog signaling pathways ([GO:0090263](https://www.ebi.ac.uk/QuickGO/term/GO:0090263), [R-HSA-5358351](https://reactome.org/content/detail/R-HSA-5358351)). Expression data reveals its significant and specific enrichment in the central nervous system, where it is a prominent marker for glial cells such as [astrocyte](/details-cell/CL0000127)s and [Schwann cell](/details-cell/CL0002573)s, suggesting a specialized role in neural development and maintenance. The gene has been identified as a new member of the glypican family and is developmentally regulated ([Link](https://doi.org/10.1006/geno.1996.4518), [Link](https://doi.org/10.1006/dbio.1997.8690)). Genetic variants may be associated with clinical conditions, as indicated by its OMIM entry ([602446](https://omim.org/entry/602446)). ## Cellular Roles and Expression Landscape The **Overall** expression profile of [GPC5](/details-gene/2262) highlights its primary role within the nervous system, particularly as a marker for glial cell populations. It shows the highest significance in [astrocyte](/details-cell/CL0000127)s (CSI: 32.59), including specific subtypes like [astrocyte of the cerebral cortex](/details-cell/CL0002605) and [Bergmann glial cell](/details-cell/CL0000644). Its high expression in [Schwann cell](/details-cell/CL0002573)s further suggests a role in both the central and peripheral nervous systems. Beyond glial cells, [GPC5](/details-gene/2262) is also significantly expressed in various neuronal subtypes, such as [pvalb GABAergic cortical interneuron](/details-cell/CL4023018) and [L2/3 intratelencephalic projecting glutamatergic neuron](/details-cell/CL4030059), indicating a broader function in neural tissue architecture and communication. Notably, significant expression is also observed in non-neural cell types, including [vascular leptomeningeal cell](/details-cell/CL4023051), which forms the protective layers of the central nervous system, and certain epithelial cells like [kidney connecting tubule epithelial cell](/details-cell/CL1000768). This latter finding is consistent with research demonstrating its developmental regulation in the kidney ([Link](https://doi.org/10.1006/dbio.1997.8690)). The gene's presence in [adipocyte](/details-cell/CL0000136)s suggests additional metabolic or structural roles outside of the nervous system. ## Pathways and Molecular Function [GPC5](/details-gene/2262) functions primarily as a cell surface co-receptor ([GO:0009986](https://www.ebi.ac.uk/QuickGO/term/GO:0009986)), mediating its effects through its heparan sulfate side chains. Its molecular activity is deeply intertwined with [Glycosaminoglycan metabolism](/details-pathway/R-HSA-1630316) ([R-HSA-1630316](https://reactome.org/content/detail/R-HSA-1630316)), particularly [HS-GAG biosynthesis](/details-pathway/R-HSA-2022928) ([R-HSA-2022928](https://reactome.org/content/detail/R-HSA-2022928)). These modifications enable [GPC5](/details-gene/2262) to bind and present signaling molecules to their respective receptors, thereby influencing key cellular decisions. This mechanism is central to its involvement in major developmental signaling cascades, including [Signaling by hedgehog](/details-pathway/R-HSA-5358351) ([R-HSA-5358351](https://reactome.org/content/detail/R-HSA-5358351)) and the [Positive regulation of canonical wnt signaling pathway](/details-go/GO0090263) ([GO:0090263](https://www.ebi.ac.uk/QuickGO/term/GO:0090263)). These roles are consistent with its high expression in astrocytes and developing neurons, where these pathways are critical for cell fate, migration ([GO:0016477](https://www.ebi.ac.uk/QuickGO/term/GO:0016477)), and synaptogenesis. Interestingly, functional annotation also implicates [GPC5](/details-gene/2262) in numerous viral infection pathways, including those for [Sars-cov-2 infection](/details-pathway/R-HSA-9694516) ([R-HSA-9694516](https://reactome.org/content/detail/R-HSA-9694516)) and [Respiratory syncytial virus infection pathway](/details-pathway/R-HSA-9820952) ([R-HSA-9820952](https://reactome.org/content/detail/R-HSA-9820952)). This suggests that the heparan sulfate chains on [GPC5](/details-gene/2262) may serve as attachment factors for these pathogens, potentially facilitating their entry into host cells. ## Research Directions Based on its distinct expression profile and functional annotations, several testable hypotheses can be proposed for [GPC5](/details-gene/2262). 1. **Role in Astrocyte-Neuron Communication:** Given its high expression in [astrocyte](/details-cell/CL0000127)s and its function in modulating Wnt and Hedgehog signaling, it is hypothesized that [GPC5](/details-gene/2262) on the astrocyte surface acts as a critical co-receptor to regulate synapse formation and maintenance. By binding and concentrating these morphogens, astrocytic [GPC5](/details-gene/2262) may control their local availability to adjacent neurons, thereby influencing synaptic plasticity. 2. **Function as a Viral Co-Receptor:** The strong association of [GPC5](/details-gene/2262) with viral entry pathways suggests it may function as a host attachment factor. We hypothesize that the heparan sulfate moieties of [GPC5](/details-gene/2262) act as an initial docking site for viruses like SARS-CoV-2 and RSV, particularly in GPC5-expressing neural cells, potentially mediating neuro-invasion or CNS-related viral pathology. To test the first hypothesis regarding its role in astrocyte-neuron signaling, a targeted experiment could be designed. CRISPR-Cas9 could be used to knock out [GPC5](/details-gene/2262) in induced pluripotent stem cell (iPSC)-derived human astrocytes. These knockout astrocytes would then be co-cultured with iPSC-derived neurons. The impact on synaptogenesis could be quantified by high-content imaging of pre-synaptic (synapsin) and post-synaptic (PSD-95) markers. Functional consequences could be measured using multi-electrode arrays to assess changes in neuronal network activity and synchronicity. As a cell surface protein with a restricted expression pattern, primarily in the CNS, [GPC5](/details-gene/2262) presents a potential therapeutic target. If found to be aberrantly expressed in neurological disorders like glioblastoma, its surface accessibility would make it an excellent candidate for targeted therapies such as antibody-drug conjugates (ADCs) or CAR-T cells. Alternatively, if its role as a viral co-receptor is confirmed, developing blocking antibodies or soluble GPC5-based decoys could represent a novel antiviral strategy to prevent viral entry into susceptible neural tissues.

Genular Protein ID: 3110600351

Symbol: GPC5_HUMAN

Name: Glypican-5

UniProtKB Accession Codes:

P78333 B2R726 O60436 Q9BX27

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 9 Ensembl 1 ExpressionAtlas 1 GO 11 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 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 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 13 RefSeq 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 9070915

Title: Characterization of glypican-5 and chromosomal localization of human GPC5, a new member of the glypican gene family.

PubMed ID: 9070915

DOI: 10.1006/geno.1996.4518

PubMed ID: 9331333

Title: Expression of the cell surface proteoglycan glypican-5 is developmentally regulated in kidney, limb, and brain.

PubMed ID: 9331333

DOI: 10.1006/dbio.1997.8690

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15057823

Title: The DNA sequence and analysis of human chromosome 13.

PubMed ID: 15057823

DOI: 10.1038/nature02379

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

Sequence Information:

  • Length: 572
  • Mass: 63707
  • Checksum: A17969FE0DD0D308
  • Sequence:
    • MDAQTWPVGF RCLLLLALVG SARSEGVQTC EEVRKLFQWR LLGAVRGLPD SPRAGPDLQV 
CISKKPTCCT RKMEERYQIA ARQDMQQFLQ TSSSTLKFLI SRNAAAFQET LETLIKQAEN 
YTSILFCSTY RNMALEAAAS VQEFFTDVGL YLFGADVNPE EFVNRFFDSL FPLVYNHLIN 
PGVTDSSLEY SECIRMARRD VSPFGNIPQR VMGQMGRSLL PSRTFLQALN LGIEVINTTD 
YLHFSKECSR ALLKMQYCPH CQGLALTKPC MGYCLNVMRG CLAHMAELNP HWHAYIRSLE 
ELSDAMHGTY DIGHVLLNFH LLVNDAVLQA HLNGQKLLEQ VNRICGRPVR TPTQSPRCSF 
DQSKEKHGMK TTTRNSEETL ANRRKEFINS LRLYRSFYGG LADQLCANEL AAADGLPCWN 
GEDIVKSYTQ RVVGNGIKAQ SGNPEVKVKG IDPVINQIID KLKHVVQLLQ GRSPKPDKWE 
LLQLGSGGGM VEQVSGDCDD EDGCGGSGSG EVKRTLKITD WMPDDMNFSD VKQIHQTDTG 
STLDTTGAGC AVATESMTFT LISVVMLLPG IW