Details for: PDGFRL

Gene ID: 5157

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: PDGFRL

Ensembl ID: ENSG00000104213

Description: platelet derived growth factor receptor like

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

  • Biological_process
    (GO:0008150)
  • Cellular_component
    (GO:0005575)
  • Extracellular region
    (GO:0005576)
  • G protein-coupled receptor signaling pathway
    (GO:0007186)
  • Platelet-derived growth factor beta-receptor activity
    (GO:0005019)
  • Platelet-derived growth factor receptor-beta signaling pathway
    (GO:0035791)
  • Platelet activating factor receptor activity
    (GO:0004992)

Significant Cells

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

  • skin fibroblast CL0002620
    CSI 9.1
    rCSI 7.85%
    PRS 99.06
  • alveolar adventitial fibroblast CL4028006
    CSI 6.57
    rCSI 10.38%
    PRS 99.56
  • bronchus fibroblast of lung CL2000093
    CSI 6.21
    rCSI 5.05%
    PRS 99.33
  • fibroblast of lung CL0002553
    CSI 5.79
    rCSI 5.39%
    PRS 99.62
  • myofibroblast cell CL0000186
    CSI 5
    rCSI 6.92%
    PRS 98.78
  • ependymal cell CL0000065
    CSI 4.98
    rCSI 10.1%
    PRS 95.11
  • keratocyte CL0002363
    CSI 4.5
    rCSI 10.81%
    PRS 99.26
  • adventitial cell CL0002503
    CSI 4.17
    rCSI 9.97%
    PRS 99.73
  • neural progenitor cell CL0011020
    CSI 3.99
    rCSI 17.56%
    PRS 95.53
  • extravillous trophoblast CL0008036
    CSI 3.25
    rCSI 4.02%
    PRS 98.68
  • chondrocyte CL0000138
    CSI 2.7
    rCSI 4.29%
    PRS 98.1
  • tendon cell CL0000388
    CSI 2.68
    rCSI 6.97%
    PRS 99.62
  • mesenchymal stem cell of adipose tissue CL0002570
    CSI 2.53
    rCSI 14.13%
    PRS 99.6
  • fibroblast CL0000057
    CSI 2.53
    rCSI 7.27%
    PRS 95.66
  • chandelier pvalb GABAergic cortical interneuron CL4023036
    CSI 1.83
    rCSI 5.74%
    PRS 97.52
  • mesenchymal cell CL0008019
    CSI 1.68
    rCSI 4.27%
    PRS 98.86
  • stromal cell of ovary CL0002132
    CSI 1.44
    rCSI 3.96%
    PRS 99.27
  • mesenchymal stem cell CL0000134
    CSI 1.2
    rCSI 13.09%
    PRS 99.45
  • L5 extratelencephalic projecting glutamatergic cortical neuron CL4023041
    CSI 0.85
    rCSI 3.05%
    PRS 96.66

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)

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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 [PDGFRL](/details-gene/5157) (Platelet-Derived Growth Factor Receptor Like) is a protein-coding gene located on chromosome 8p22. It encodes a protein that shares homology with the extracellular domain of the Platelet-Derived Growth Factor Receptor Beta. Expression data from the **Overall** context indicates that [PDGFRL](/details-gene/5157) is a prominent marker for various mesenchymal cell types, particularly fibroblasts. Its high significance in cells such as [skin fibroblast](/details-cell/CL0002620), [alveolar adventitial fibroblast](/details-cell/CL4028006), and [myofibroblast cell](/details-cell/CL0000186) suggests a fundamental role in connective tissue biology, tissue remodeling, and structural integrity. Research has implicated [PDGFRL](/details-gene/5157) as a candidate tumor suppressor gene and has associated genetic variants with susceptibility to Behcet's disease ([Link](https://pubmed.ncbi.nlm.nih.gov/7898930/), [Link](https://doi.org/10.1002/humu.22208)). ## Cellular Roles and Expression Landscape The expression profile of [PDGFRL](/details-gene/5157) strongly establishes its identity as a key gene in mesenchymal and stromal cell populations. In the **Overall** biological context, it exhibits the highest significance in multiple fibroblast subtypes, including [skin fibroblast](/details-cell/CL0002620) (CSI: 9.10), [alveolar adventitial fibroblast](/details-cell/CL4028006) (CSI: 6.57), [bronchus fibroblast of lung](/details-cell/CL2000093) (CSI: 6.21), and [fibroblast of lung](/details-cell/CL0002553) (CSI: 5.79). This pattern is further supported by high significance in functionally related cells such as [myofibroblast cell](/details-cell/CL0000186), [keratocyte](/details-cell/CL0002363) (corneal fibroblasts), [adventitial cell](/details-cell/CL0002503), and [mesenchymal stem cell of adipose tissue](/details-cell/CL0002570). Beyond its core fibroblast identity, [PDGFRL](/details-gene/5157) also shows notable significance in other specialized structural or progenitor cells, including [ependymal cell](/details-cell/CL0000065), [chondrocyte](/details-cell/CL0000138), and [neural progenitor cell](/details-cell/CL0011020). This suggests a broader role in the development and maintenance of various structural and neural tissues. The consistent, high-level expression across these related cell types indicates that [PDGFRL](/details-gene/5157) may be integral to the fundamental biological processes governing mesenchymal cell function. ## Pathways and Molecular Function Functional annotations are consistent with the gene's name and observed cellular expression patterns. [PDGFRL](/details-gene/5157) is associated with the [platelet-derived growth factor receptor-beta signaling pathway](/details-cell/GO:0035791) and possesses predicted [platelet-derived growth factor beta-receptor activity](/details-cell/GO:0005019). This implicates it in cellular responses to PDGF, a critical growth factor for cells of mesenchymal origin, regulating processes like proliferation, migration, and differentiation. Its annotation to the [extracellular region](/details-cell/GO:0005576) aligns with its role as a receptor-like protein that interacts with the cellular microenvironment. The high expression in fibroblasts, which are primary targets of PDGF signaling in processes like wound healing and fibrosis, strongly reinforces the biological relevance of these annotated pathways. It is also linked to the [G protein-coupled receptor signaling pathway](/details-cell/GO:0007186), suggesting it may modulate cell signaling through diverse mechanisms. ## Research Directions The existing evidence positions [PDGFRL](/details-gene/5157) as a critical modulator of mesenchymal cell biology with potential roles in cancer and autoimmune disease. Its frequent deletion in tumors and specific association with Behcet's disease warrants further investigation. ### Proposed Hypotheses 1. **Tumor Suppressor Function in Fibroblasts:** The loss of [PDGFRL](/details-gene/5157) expression in stromal fibroblasts, such as [skin fibroblast](/details-cell/CL0002620), dysregulates PDGF signaling pathways, promoting their transition into a pro-tumorigenic, cancer-associated fibroblast (CAF) phenotype. This phenotypic switch contributes to cancer progression by remodeling the extracellular matrix and secreting growth factors that support tumor cell invasion. 2. **Role in Vascular Pathology of Behcet's Disease:** Genetic variants of [PDGFRL](/details-gene/5157) linked to Behcet's disease ([Link](https://doi.org/10.1002/humu.22208)) may alter its function in perivascular cells like [adventitial cell](/details-cell/CL0002503). This could lead to an aberrant response to vascular injury or inflammatory cues, contributing to the vasculitis that is a hallmark of the disease. ### Key Experimental Approach To test the hypothesis that [PDGFRL](/details-gene/5157) acts as a tumor suppressor in the tumor microenvironment, one could perform a CRISPR-Cas9-mediated knockout of [PDGFRL](/details-gene/5157) in primary human dermal fibroblasts. These engineered fibroblasts and their wild-type counterparts could then be co-cultured with melanoma cells in a 3D skin organoid model. The impact of [PDGFRL](/details-gene/5157) loss would be assessed by measuring changes in fibroblast activation markers (e.g., alpha-SMA expression), secretion of pro-inflammatory cytokines (e.g., IL-6) and matrix metalloproteinases (MMPs), and the subsequent effect on melanoma cell invasion and proliferation via immunofluorescence microscopy and functional assays. ### Therapeutic Potential Given its proposed role as a tumor suppressor, the therapeutic goal would be to restore or mimic the function of [PDGFRL](/details-gene/5157), rather than inhibit it. This presents a significant challenge. However, if [PDGFRL](/details-gene/5157) functions as a decoy receptor that sequesters a pro-fibrotic or pro-tumorigenic ligand, administering a recombinant soluble form of its extracellular domain could be a viable strategy to neutralize that ligand's activity. In the context of cancer, gene therapy approaches aimed at re-introducing [PDGFRL](/details-gene/5157) expression in the tumor stroma could be a long-term possibility, although such strategies face substantial delivery and safety hurdles.

Genular Protein ID: 4119528063

Symbol: PGFRL_HUMAN

Name: Platelet-derived growth factor receptor-like protein

UniProtKB Accession Codes:

Q15198 A8K085 Q6FH04

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 5 Ensembl 2 ExpressionAtlas 1 GO 3 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 2 STRING 1 SUPFAM 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 7898930

Title: Isolation of a candidate tumor suppressor gene on chromosome 8p21.3-p22 that is homologous to an extracellular domain of the PDGF receptor beta gene.

PubMed ID: 7898930

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 19815557

Title: Cytoplasmic ACK1 interaction with multiple receptor tyrosine kinases is mediated by Grb2: an analysis of ACK1 effects on Axl signaling.

PubMed ID: 19815557

DOI: 10.1074/jbc.m109.072660

PubMed ID: 22926996

Title: Genetic variant on PDGFRL associated with Behcet disease in Chinese Han populations.

PubMed ID: 22926996

DOI: 10.1002/humu.22208

Sequence Information:

  • Length: 375
  • Mass: 41861
  • Checksum: DF7FE6EB3FB2A802
  • Sequence:
    • MKVWLLLGLL LVHEALEDVT GQHLPKNKRP KEPGENRIKP TNKKVKPKIP KMKDRDSANS 
APKTQSIMMQ VLDKGRFQKP AATLSLLAGQ TVELRCKGSR IGWSYPAYLD TFKDSRLSVK 
QNERYGQLTL VNSTSADTGE FSCWVQLCSG YICRKDEAKT GSTYIFFTEK GELFVPSPSY 
FDVVYLNPDR QAVVPCRVTV LSAKVTLHRE FPAKEIPANG TDIVYDMKRG FVYLQPHSEH 
QGVVYCRAEA GGRSQISVKY QLLYVAVPSG PPSTTILASS NKVKSGDDIS VLCTVLGEPD 
VEVEFTWIFP GQKDERPVTI QDTWRLIHRG LGHTTRISQS VITVEDFETI DAGYYICTAQ 
NLQGQTTVAT TVEFS