Details for: CR1L

Gene ID: 1379

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: CR1L

Ensembl ID: ENSG00000197721

Description: complement C3b/C4b receptor 1 like

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • renal alpha-intercalated cell CL0005011
    CSI 3.54
    rCSI 4.74%
    PRS 99.32
  • erythrocyte CL0000232
    CSI 3.15
    rCSI 7.15%
    PRS 98.4
  • primitive red blood cell CL0002355
    CSI 2.18
    rCSI 11.76%
    PRS 99.13
  • basal cell of epidermis CL0002187
    CSI 1.99
    rCSI 3.53%
    PRS 88.12
  • erythroid lineage cell CL0000764
    CSI 1.64
    rCSI 10.55%
    PRS 98.37
  • endothelial cell of placenta CL0009092
    CSI 1.47
    rCSI 7.23%
    PRS 99.24
  • erythroblast CL0000765
    CSI 1.4
    rCSI 3.71%
    PRS 98.85
  • melanocyte of skin CL1000458
    CSI 1.28
    rCSI 1.74%
    PRS 89.48
  • megakaryocyte CL0000556
    CSI 1
    rCSI 4.34%
    PRS 98.19

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):
    • 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 [CR1L](/details-gene/1379) (complement C3b/C4b receptor 1 like) is a protein-coding gene located on chromosome 1q32.2. As its name suggests, it is a paralog of the well-characterized complement receptor 1 (CR1). Functional annotations indicate that [CR1L](/details-gene/1379) is primarily involved in the negative regulation of the complement system, a critical component of the innate immune response. **Overall** expression data highlight its significant role in specific, distinct cell populations, showing the highest significance in [renal alpha-intercalated cells](/details-cell/CL0005011) and cells of the erythroid lineage, including mature [erythrocytes](/details-cell/CL0000232) and their precursors. This expression pattern suggests a specialized function in protecting certain tissues from complement-mediated damage. ## Cellular Roles and Expression Landscape The expression profile of [CR1L](/details-gene/1379) points to a highly specialized role in two primary biological systems: the kidney and the hematopoietic system. The most significant expression is observed in [renal alpha-intercalated cells](/details-cell/CL0005011) (CSI: 3.54), suggesting a key function in regulating local complement activity within the kidney tubules. A second major site of [CR1L](/details-gene/1379) significance is within the hematopoietic system, particularly the erythroid lineage. It is highly significant in mature [erythrocytes](/details-cell/CL0000232) (CSI: 3.15), [primitive red blood cells](/details-cell/CL0002355) (CSI: 2.18), [erythroid lineage cells](/details-cell/CL0000764) (CSI: 1.64), and [erythroblasts](/details-cell/CL0000765) (CSI: 1.40). This is consistent with early research identifying its expression in hematopoietic tissues ([Link](https://doi.org/10.1016/j.molimm.2003.09.010)) and suggests a role in protecting these cells from complement-mediated lysis throughout their development and circulation. Its significance in [megakaryocytes](/details-cell/CL0000556) (CSI: 1.00) further supports its role in hematopoiesis. Additionally, [CR1L](/details-gene/1379) shows moderate but notable significance in other specialized cell types, including [basal cells of the epidermis](/details-cell/CL0002187) and [melanocytes of the skin](/details-cell/CL1000458), as well as [endothelial cells of the placenta](/details-cell/CL0009092), indicating its function may extend to providing complement regulation at key biological barriers. ## Pathways and Molecular Function The functional annotations for [CR1L](/details-gene/1379) strongly align with its identity as a complement regulatory protein. Its primary biological processes involve the negative regulation of the classical complement pathway ([GO:0045959](https://www.ebi.ac.uk/QuickGO/term/GO:0045959)), the general regulation of complement activation ([GO:0030449](https://www.ebi.ac.uk/QuickGO/term/GO:0030449)), and the regulation of complement-dependent cytotoxicity ([GO:1903659](https://www.ebi.ac.uk/QuickGO/term/GO:1903659)). This implicates the [CR1L](/details-gene/1379) protein in mechanisms that prevent excessive or inappropriate activation of this powerful immune cascade. The protein's molecular function is broadly categorized as [protein binding](/details-cell/GO:0005515), which is consistent with its role as a receptor for complement components C3b and/or C4b. Cellular component analysis places the protein at the [plasma membrane](/details-cell/GO:0005886) and within [receptor complexes](/details-cell/GO:0043235), which is the expected location for a surface receptor. Its annotation to the [extracellular space](/details-cell/GO:0005615) and [cytoplasm](/details-cell/GO:0005737) may suggest the existence of soluble variants or intracellular domains involved in signaling. While the gene is also annotated to [T cell mediated immunity](/details-cell/GO:0002456), its low expression in T-cell populations suggests this may be an indirect role or one that is relevant only in specific contexts not captured in this dataset. ## Research Directions The specific and high-level expression of [CR1L](/details-gene/1379) in distinct cell populations, combined with its clear function as a complement inhibitor, provides fertile ground for further investigation into its role in health and disease. **Proposed Testable Hypotheses:** 1. **Hypothesis 1:** Given its top significance in [renal alpha-intercalated cells](/details-cell/CL0005011), [CR1L](/details-gene/1379) acts as a critical local guardian, protecting the distal nephron from complement-mediated damage in inflammatory kidney diseases such as lupus nephritis or ischemic-reperfusion injury. 2. **Hypothesis 2:** In the erythroid lineage, [CR1L](/details-gene/1379) functions as a key cell-surface protein that, similar to its paralog CR1, protects circulating [erythrocytes](/details-cell/CL0000232) from premature clearance by the complement system. Its deficiency could contribute to certain forms of hemolytic anemia. **Proposed Key Experiment:** To test **Hypothesis 1**, the role of [CR1L](/details-gene/1379) in renal protection could be investigated using a mouse model. A conditional knockout of *Cr1l* specifically in renal tubular epithelial cells would be generated. These mice, alongside wild-type controls, would be subjected to a model of complement-driven kidney disease, such as nephrotoxic serum nephritis. The primary outcomes would be the quantification of C3b/C4b deposition on tubular cells, measurement of proteinuria, and histological assessment of tubular injury and inflammation. A significant increase in these metrics in the knockout mice would confirm the protective role of [CR1L](/details-gene/1379). **Therapeutic Potential:** As a negative regulator of the complement system located on the cell surface, [CR1L](/details-gene/1379) presents an attractive therapeutic target. The strategy would focus on **activation** or supplementation rather than inhibition. For diseases characterized by excessive complement activation, such as atypical hemolytic uremic syndrome or paroxysmal nocturnal hemoglobinuria, a recombinant soluble form of [CR1L](/details-gene/1379) could act as a potent systemic complement inhibitor. Alternatively, for kidney diseases, gene therapy approaches aimed at overexpressing [CR1L](/details-gene/1379) specifically in renal cells could provide a localized and durable protective effect against complement-mediated pathology.

Genular Protein ID: 1492668767

Symbol: CR1L_HUMAN

Name: Complement component receptor 1-like protein

UniProtKB Accession Codes:

Q2VPA4 Q32MC9 Q8NEU7

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 ExpressionAtlas 1 GO 8 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 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 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 16710414

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

PubMed ID: 16710414

DOI: 10.1038/nature04727

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: 14687939

Title: A human CR1-like transcript containing sequence for a binding protein for iC4 is expressed in hematopoietic and fetal lymphoid tissue.

PubMed ID: 14687939

DOI: 10.1016/j.molimm.2003.09.010

Sequence Information:

  • Length: 569
  • Mass: 62714
  • Checksum: D49F7517E1347A5D
  • Sequence:
    • MAPPVRLERP FPSRRFPGLL LAALVLLLSS FSDQCNVPEW LPFARPTNLT DDFEFPIGTY 
LNYECRPGYS GRPFSIICLK NSVWTSAKDK CKRKSCRNPP DPVNGMAHVI KDIQFRSQIK 
YSCPKGYRLI GSSSATCIIS GNTVIWDNKT PVCDRIICGL PPTIANGDFT SISREYFHYG 
SVVTYHCNLG SRGKKVFELV GEPSIYCTSK DDQVGIWSGP APQCIIPNKC TPPNVENGIL 
VSDNRSLFSL NEVVEFRCQP GFGMKGPSHV KCQALNKWEP ELPSCSRVCQ PPPDVLHAER 
TQRDKDNFSP GQEVFYSCEP GYDLRGSTYL HCTPQGDWSP AAPRCEVKSC DDFLGQLPNG 
HVLFPLNLQL GAKVDFVCDE GFQLKGSSAS YCVLAGMESL WNSSVPVCER KSCETPPVPV 
NGMVHVITDI HVGSRINYSC TTGHRLIGHS SAECILSGNT AHWSMKPPIC QQIFCPNPPA 
ILNGRHTGTP LGDIPYGKEV SYTCDPHPDR GMTFNLIGES TIRRTSEPHG NGVWSSPAPR 
CELPVGAGSH DALIVGKFYE VFAEEFCHL