CD47 (Cluster of Differentiation 47) Gene: Role in Cancer Immunotherapy and Thrombospondin-1 Signaling
A comprehensive biomedical resource on CD47 gene, protein function, expression, mutations, and clinical relevance in oncology and beyond.
Gene Information Card
| Symbol | CD47 |
|---|---|
| Full Name | CD47 molecule |
| Gene Type | protein coding |
| Chromosomal Location | 3q13.12 |
| NCBI Gene ID | 961 ncbi.nlm.nih.gov/gene/961 |
| Ensembl ID | ENSG00000196776 |
| UniProt ID | Q08722 |
| OMIM ID | 601028 |
| HGNC ID | 1682 |
| Aliases | IAP, MER6, OA3, integrin-associated protein, CD47 antigen |
Description
The CD47 gene encodes a transmembrane glycoprotein belonging to the immunoglobulin superfamily. It is ubiquitously expressed on the cell surface and functions as a 'don't eat me' signal by interacting with signal regulatory protein alpha (SIRPα) on macrophages, thereby inhibiting phagocytosis. CD47 also binds thrombospondin-1 (TSP-1) and integrins, modulating cell migration, adhesion, and apoptosis. Overexpression of CD47 is observed in many cancers, enabling immune evasion, and it is a major target for cancer immunotherapy. Additionally, CD47 plays roles in erythrocyte clearance, platelet homeostasis, and vascular biology.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Overexpression of CD47 on tumor cells binds SIRPα on macrophages, delivering an anti-phagocytic signal that promotes immune evasion and tumor progression. | High CD47 expression correlates with poor prognosis in various cancers; anti-CD47 antibodies are in clinical trials (e.g., magrolimab). |
| Hematologic malignancies (AML, NHL) | CD47 is highly expressed on leukemic stem cells and lymphoma cells, protecting them from phagocytosis and contributing to disease persistence. | Preclinical and clinical studies show that CD47 blockade enhances tumor cell clearance and improves survival in AML and NHL models. |
| Thrombocytopenia and platelet disorders | CD47 on platelets interacts with TSP-1 and SIRPα, influencing platelet activation and clearance; altered CD47 expression may contribute to platelet dysfunction. | Studies in CD47-deficient mice show thrombocytopenia and altered platelet responses, suggesting a regulatory role. |
| Atherosclerosis | CD47 expression is upregulated in atherosclerotic plaques, impairing efferocytosis (clearance of apoptotic cells) and promoting plaque necrosis. | CD47 blockade reduces atherosclerosis in mouse models by enhancing efferocytosis. |
| Ischemia-reperfusion injury | CD47-mediated inhibition of phagocytosis impairs clearance of dead cells after ischemic injury, exacerbating tissue damage. | CD47 knockout or blockade reduces infarct size in models of myocardial and cerebral ischemia. |
| Autoimmune diseases (e.g., SLE) | CD47 may modulate immune tolerance and clearance of apoptotic cells, with altered expression contributing to autoimmunity. | Polymorphisms in CD47 have been associated with susceptibility to systemic lupus erythematosus in some studies. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | High | High |
| Bone Marrow | High | High |
| Spleen | High | High |
| Lung | Medium | Medium |
| Liver | Medium | Medium |
| Kidney | Medium | Medium |
| Brain | Low | Low |
| Heart | Low | Low |
| Muscle | Low | Low |
| Pancreas | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | High | Overexpressed, contributes to immune evasion |
| MCF7 (breast cancer) | High | High expression associated with poor prognosis |
| A549 (lung cancer) | Medium | Moderate expression, target for therapy |
| Jurkat (T-cell leukemia) | High | Expressed on leukemic cells |
| THP-1 (monocytic leukemia) | High | Expressed on myeloid cells |
| HUVEC (endothelial) | Medium | Expressed on vascular endothelium |
| HEK293 (embryonic kidney) | Medium | Commonly used for recombinant expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.276C>T (p.Ser92Phe) | Missense | Rare (0.01% in gnomAD) | Alters ligand binding; functional impact unclear |
| c.469G>A (p.Val157Met) | Missense | Rare (0.005% in gnomAD) | Potential effect on protein stability |
| c.782A>G (p.Asn261Ser) | Missense | Rare (0.002% in gnomAD) | Located in cytoplasmic domain; may affect signaling |
| c.1000C>T (p.Arg334Trp) | Missense | Rare (0.001% in gnomAD) | In transmembrane domain; possible impact on membrane localization |
| Copy number gain | CNV | Frequent in cancers (e.g., 10-20% in solid tumors) | Increased CD47 expression, immune evasion |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CD47 are rare and not well characterized. Complete knockout in mice leads to thrombocytopenia, anemia, and increased susceptibility to autoimmune hemolysis, indicating a critical role in erythrocyte homeostasis and immune regulation.
Gain of Function (GOF)
Gain-of-function is primarily achieved through gene amplification or transcriptional upregulation, leading to CD47 overexpression on tumor cells. This enhances the anti-phagocytic signal, promoting immune evasion and tumor progression.
Dominant Negative (DN)
No dominant-negative mutations have been reported for CD47. The protein functions as a monomer; however, altered splicing or truncating mutations could potentially interfere with normal signaling, but such variants are not documented in major databases.
View complete mutation data：
Gene Ontology (GO)
Pathways
• CD47/SIRPα signaling pathway (phagocytosis checkpoint)
• Thrombospondin-1 signaling via CD47
• Integrin signaling pathway
• Regulation of actin cytoskeleton
• Apoptosis and survival signaling
• Immune evasion in cancer
Protein Summary
The CD47 protein (also known as integrin-associated protein, IAP) is a 50 kDa transmembrane glycoprotein with an extracellular N-terminal immunoglobulin variable-type domain, five transmembrane segments, and a short cytoplasmic tail. It is ubiquitously expressed and interacts with multiple ligands: SIRPα (signal regulatory protein alpha) on phagocytes, thrombospondin-1 (TSP-1), and integrins (e.g., αvβ3). The interaction with SIRPα initiates a 'don't eat me' signal that inhibits phagocytosis, while TSP-1 binding modulates cell survival, migration, and angiogenesis. CD47 is involved in immune homeostasis, red blood cell clearance, and platelet function. In cancer, CD47 is overexpressed, enabling tumor cells to evade immune surveillance. Therapeutic strategies targeting CD47, such as anti-CD47 antibodies, are being developed to enhance tumor phagocytosis. The protein also plays roles in vascular biology and inflammation, making it a versatile therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CD47 Knockout HEK293 Cell Line | EDJ-KQ1969 | Human | 961 | Details Get a Quote |
| CD47 Knockout HCT 116 Cell Line | EDJ-KQ21938 | Human | 961 | Details Get a Quote |
| CD47 Knockout HeLa Cell Line | EDJ-KQ21939 | Human | 961 | Details Get a Quote |
| CD47 Knockout A-549 Cell Line | EDJ-KQ18228 | Human | 961 | Details Get a Quote |
| Cd47 Knockout MC-38 Cell Line | EDJ-KZ142 | Mouse | 16423 | Details Get a Quote |
| CD47 Knockout Jurkat Cell Line | EDJ-KQ78072 | Human | 961 | Details Get a Quote |
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