CD59 (CD59 Molecule / Protectin): Complement Regulation, PNH, and Beyond
A comprehensive biomedical guide to the CD59 gene, its protein product (protectin), role in complement regulation, associated diseases like Paroxysmal Nocturnal Hemoglobinuria (PNH), and its significance in cancer and immunotherapy.
Gene Information Card
| Symbol | CD59 |
|---|---|
| Full Name | CD59 Molecule (CD59 blood group) |
| Gene Type | Protein coding |
| Chromosomal Location | 11p13 |
| NCBI Gene ID | 966 ncbi.nlm.nih.gov/gene/966 |
| Ensembl ID | ENSG00000085063 |
| UniProt ID | P13987 |
| OMIM ID | 107271 |
| HGNC ID | 1689 |
| Aliases | 16.3A5, 1F5, EJ16, EJ30, EL32, G344, HRF20, MACIF, MEM43, MIC11, MIN1, MIN2, MIN3, MIRL, MSK21, p18-20 |
Description
The CD59 gene encodes CD59, a potent glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein known as protectin. It functions as a key inhibitor of the complement system, specifically blocking the assembly of the Membrane Attack Complex (MAC). By binding to complement components C8 and C9, CD59 prevents the formation of the lytic pore, thereby protecting host cells from complement-mediated lysis. CD59 is widely expressed on all circulating cells and in most tissues. Deficiencies in CD59, often due to somatic mutations in the PIGA gene affecting GPI anchor synthesis, are central to the pathophysiology of Paroxysmal Nocturnal Hemoglobinuria (PNH). Beyond its canonical role in complement regulation, CD59 is implicated in T-cell activation, cellular signaling, and is frequently overexpressed in various cancers, contributing to immune evasion.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Paroxysmal Nocturnal Hemoglobinuria (PNH) | Somatic mutations in the PIGA gene lead to a deficiency of GPI-anchored proteins, including CD59 and CD55, on hematopoietic stem cells. The lack of CD59 on red blood cells renders them susceptible to complement-mediated lysis, leading to intravascular hemolysis, thrombosis, and anemia. | OMIM #300818, ClinVar, PMID: 10807685 |
| CD59 Deficiency (C9D9) | Rare inherited homozygous or compound heterozygous mutations in the CD59 gene itself cause a severe neurological syndrome characterized by chronic hemolysis, recurrent peripheral demyelinating neuropathy, and stroke-like episodes. The loss of CD59 function leads to uncontrolled MAC formation on erythrocytes and Schwann cells. | OMIM #612300, PMID: 23348765 |
| Cancer (Various) | CD59 is frequently overexpressed in many solid tumors (e.g., breast, lung, colorectal, melanoma) and hematological malignancies. This overexpression protects tumor cells from complement-dependent cytotoxicity (CDC) mediated by monoclonal antibody therapies and the innate immune system, contributing to tumor immune evasion and therapy resistance. | COSMIC, PMID: 31530866 |
| Atherosclerosis | CD59 expression is reduced in the vascular endothelium of atherosclerotic plaques, leading to increased MAC deposition and chronic inflammation, which contributes to the progression of the disease. | PMID: 16968948 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | High | High |
| Bone Marrow | High | High |
| Spleen | High | High |
| Lymph Node | High | High |
| Liver | Medium | Medium |
| Lung | Medium | Medium |
| Kidney | Medium | Medium |
| Brain | Low | Low |
| Heart | Medium | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (Leukemia) | High | High expression of GPI-anchored CD59 |
| A549 (Lung Carcinoma) | High | Overexpressed to evade complement |
| MCF7 (Breast Carcinoma) | Medium | Expression correlates with resistance to trastuzumab |
| HUVEC (Endothelial) | High | Protects against complement attack |
| HepG2 (Liver Carcinoma) | Medium | Constitutive expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.146C>T (p.Thr49Ile) | Missense | Rare | Associated with inherited CD59 deficiency; disrupts protein function and leads to MAC susceptibility. |
| c.271A>G (p.Asn91Asp) | Missense | Rare | Reported in CD59 deficiency; affects GPI-anchoring or protein stability. |
| PIGA mutations (e.g., c.1234C>T) | Somatic | Common in PNH | Not a mutation in CD59 itself, but causes loss of GPI anchor, leading to CD59 deficiency on affected clones. |
| Copy Number Gain | CNV | Frequent in tumors | Amplification of the CD59 locus leads to protein overexpression and immune evasion in cancer. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CD59 (e.g., missense mutations in inherited deficiency) or loss of GPI-anchoring (due to PIGA mutations in PNH) result in the absence of functional CD59 on the cell surface. This leads to uncontrolled MAC formation, complement-mediated cell lysis, and the clinical phenotypes of PNH and CD59 deficiency.
Gain of Function (GOF)
Gain-of-function is primarily observed as overexpression of the wild-type CD59 protein in cancer cells. This is often due to gene amplification or transcriptional upregulation. The increased CD59 levels enhance the cell's resistance to complement-mediated killing, promoting tumor survival and resistance to antibody-based therapies.
Dominant Negative (DN)
No clear dominant-negative mutations have been described for CD59. The inherited deficiency is typically autosomal recessive, requiring biallelic mutations to abolish function. The somatic PIGA mutations in PNH are also recessive at the cellular level, as the remaining normal X chromosome in females can still produce functional protein.
View complete mutation data：
Gene Ontology (GO)
| • complement binding | • complement component C8 binding |
| • complement component C9 binding | • protein binding |
| • regulation of complement activation | • innate immune response |
| • cytolysis | • cell surface |
| • extracellular exosome | • anchored component of membrane |
| • plasma membrane | • negative regulation of complement-dependent cytotoxicity |
| • negative regulation of cytolysis | • positive regulation of T cell activation |
Pathways
• Complement cascade
• Immune System
• Innate Immune System
• Regulation of Complement pathway
• CD59 mediated inhibition of MAC
Protein Summary
CD59, also known as protectin, is a small (18-20 kDa) glycoprotein anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor. Its primary function is to protect host cells from damage by the complement system. It achieves this by binding to the C8 and C9 components of the assembling Membrane Attack Complex (MAC), thereby preventing the incorporation of multiple C9 molecules and the formation of a lytic pore. This action is crucial for the survival of autologous cells during complement activation. CD59 is widely expressed on erythrocytes, leukocytes, platelets, endothelial cells, and epithelial cells. Besides its complement-inhibitory role, CD59 is involved in signal transduction pathways, particularly in T-cell activation, where it associates with protein tyrosine kinases. In the context of disease, CD59 deficiency is a hallmark of PNH, and its overexpression in tumors is a significant mechanism of immune evasion, making it a target for cancer therapy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CD59 Knockout HEK293 Cell Line | EDJ-KQ50178 | Human | 966 | Details Get a Quote |
| CD59 Knockout HeLa Cell Line | EDJ-KQ52845 | Human | 966 | Details Get a Quote |
| CD59 Knockout A-549 Cell Line | EDJ-KQ61312 | Human | 966 | Details Get a Quote |
| CD59 Knockout HCT 116 Cell Line | EDJ-KQ69806 | Human | 966 | Details Get a Quote |
| CD46 and CD55 and CD59 Knockout HEK293 Cell Line | EDC08362 | Human | 4179 and 1604 and 966 | Details Get a Quote |
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