CR1 (Complement C3b/C4b Receptor 1) Gene
A comprehensive biomedical overview of the CR1 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | CR1 |
|---|---|
| Full Name | Complement C3b/C4b Receptor 1 (Knops blood group) |
| Gene Type | protein-coding |
| Chromosomal Location | 1q32.2 |
| NCBI Gene ID | 1378 ncbi.nlm.nih.gov/gene/1378 |
| Ensembl ID | ENSG00000203710 |
| UniProt ID | P17927 |
| OMIM ID | 120620 |
| HGNC ID | 2334 |
| Aliases | C3BR, C4BR, CD35, KNOP |
Description
The CR1 gene encodes complement receptor type 1 (CR1/CD35), a transmembrane glycoprotein primarily expressed on erythrocytes, leukocytes, and other cells. CR1 binds complement components C3b and C4b, mediating immune clearance, regulation of complement activation, and immune adherence. It is involved in the innate immune response and has been implicated in various diseases, including malaria, Alzheimer's disease, and autoimmune disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Malaria (Plasmodium falciparum) | CR1 on erythrocytes mediates rosetting of infected red blood cells, contributing to severe malaria pathology. | PMID: 12707385; PMID: 15634952 |
| Alzheimer's disease | CR1 variants (e.g., rs6656401) are associated with increased risk; CR1 may influence amyloid-beta clearance and neuroinflammation. | PMID: 19734903; PMID: 21460841 |
| Systemic lupus erythematosus (SLE) | Reduced CR1 expression on erythrocytes leads to impaired immune complex clearance, contributing to disease pathogenesis. | PMID: 15312286; PMID: 10902718 |
| Age-related macular degeneration (AMD) | CR1 polymorphisms (e.g., rs6656401) are associated with AMD risk, possibly via complement dysregulation. | PMID: 20385826; PMID: 21738002 |
| Hereditary erythroblastic multinuclearity with positive acidified serum lysis test (HEMPAS) | Not directly associated; CR1 deficiency may affect complement regulation but is not a primary cause. | Not established |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | High (nTPM ~ 200) | High expression in whole blood, particularly on erythrocytes and leukocytes. |
| Spleen | Moderate (nTPM ~ 50) | Expression in splenic macrophages and lymphocytes. |
| Liver | Low (nTPM ~ 10) | Low expression in hepatocytes; mainly in Kupffer cells. |
| Lung | Low (nTPM ~ 5) | Low expression in alveolar macrophages. |
| Brain | Very low (nTPM < 1) | Minimal expression in brain tissue; mainly in microglia. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Erythrocytes | High | CR1 is highly expressed on red blood cells, mediating immune adherence. |
| Monocytes | High | CR1 is expressed on monocytes and involved in phagocytosis. |
| B lymphocytes | Moderate | CR1 is present on B cells, contributing to immune regulation. |
| T lymphocytes | Low | CR1 expression is low on T cells. |
| HEK293 | Low | Low endogenous expression; often used for transfection studies. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs6656401 (intronic) | SNP | Risk allele frequency ~0.2 in European populations | Associated with increased Alzheimer's disease risk; may affect CR1 expression or splicing. |
| rs3818361 (intronic) | SNP | Risk allele frequency ~0.3 | Associated with Alzheimer's disease and AMD. |
| Knops blood group variants (e.g., McC(a/b), Sl(a)) | Missense | Variable | Affect CR1 antigenicity; may influence malaria susceptibility. |
| CR1*1/CR1*2 (size polymorphism) | Structural variant | Common | CR1*2 has reduced expression and is associated with SLE. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CR1 are rare; reduced expression or function leads to impaired immune complex clearance and complement regulation, contributing to autoimmune diseases like SLE.
Gain of Function (GOF)
No clear gain-of-function mutations have been described; some variants may increase CR1 expression, potentially enhancing complement regulation but with unclear clinical impact.
Dominant Negative (DN)
No dominant-negative mutations have been reported for CR1.
View complete mutation data：
Gene Ontology (GO)
| • receptor activity (GO:0004872) | • protein binding (GO:0005515) |
| • plasma membrane (GO:0005886) | • complement activation (GO:0006956) |
| • complement activation, classical pathway (GO:0006958) | • single fertilization (GO:0007338) |
| • integral component of membrane (GO:0016021) | • regulation of complement activation (GO:0030449) |
| • defense response to Gram-negative bacterium (GO:0050829) |
Pathways
• Complement cascade (KEGG: hsa04610)
• Immune system (Reactome: R-HSA-168256)
• Innate immune system (Reactome: R-HSA-168249)
Protein Summary
CR1 is a large type I transmembrane glycoprotein (~200-250 kDa) with multiple complement control protein (CCP) repeats. It binds C3b and C4b, acting as a cofactor for factor I-mediated cleavage, and facilitates immune adherence and phagocytosis. CR1 is also a receptor for C1q and mannose-binding lectin, and it plays a role in regulating both classical and alternative complement pathways. The protein is expressed on erythrocytes, leukocytes, and other cells, and its extracellular domain is organized into four long homologous repeats (LHRs) that contain binding sites for C3b/C4b and other ligands.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TACR1 Knockout HEK293 Cell Line | EDC90448 | Human | 6869 | Details Get a Quote |
| DECR1 Knockout HEK293 Cell Line | EDJ-KQ955 | Human | 1666 | Details Get a Quote |
| CXCR1 Knockout HEK293 Cell Line | EDJ-KQ1723 | Human | 3577 | Details Get a Quote |
| NCR1 Knockout HEK293 Cell Line | EDJ-KQ3178 | Human | 9437 | Details Get a Quote |
| CCR10 Knockout HEK293 Cell Line | EDJ-KQ3228 | Human | 2826 | Details Get a Quote |
| PYCR1 Knockout HEK293 Cell Line | EDJ-KQ3381 | Human | 5831 | Details Get a Quote |
| CX3CR1 Knockout HEK293 Cell Line | EDJ-KQ3859 | Human | 1524 | Details Get a Quote |
| CCR1 Knockout HEK293 Cell Line | EDJ-KQ4300 | Human | 1230 | Details Get a Quote |
| CR1 Knockout HEK293 Cell Line | EDJ-KQ4336 | Human | 1378 | Details Get a Quote |
| CR1L Knockout HEK293 Cell Line | EDJ-KQ4339 | Human | 1379 | Details Get a Quote |
| XCR1 Knockout HEK293 Cell Line | EDJ-KQ4756 | Human | 2829 | Details Get a Quote |
| AMMECR1 Knockout HEK293 Cell Line | EDJ-KQ6187 | Human | 9949 | Details Get a Quote |
| FLVCR1 Knockout HEK293 Cell Line | EDJ-KQ8951 | Human | 28982 | Details Get a Quote |
| UQCR10 Knockout HEK293 Cell Line | EDJ-KQ9048 | Human | 29796 | Details Get a Quote |
| AMMECR1L Knockout HEK293 Cell Line | EDJ-KQ9870 | Human | 83607 | Details Get a Quote |
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