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CD59
CD59 molecule (CD59 blood group)
CD59 is located on the short (p) arm of chromosome 11, at band 11p13. Arm ratio per GRCh38 - banding schematic.
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Overview
CD59, located on chromosome 11p13, encodes a glycosylphosphatidylinositol-anchored membrane protein that serves a vital protective function in human cells. The protein regulates the terminal stage of the complement system, a component of innate immunity that can destroy cells by forming membrane attack complexes. Without functional CD59, the complement cascade may inappropriately target the body's own red blood cells, nerve cells, and other tissues, leading to haemolytic conditions and immune dysregulation.
Pathogenic variants in CD59 are inherited in an autosomal recessive pattern, meaning affected individuals carry alterations in both gene copies. The gene appears on multiple NHS clinical panels related to immune deficiency, haematological disorders, and neuropathy, reflecting its broad role in protecting diverse cell types from complement-mediated injury.
What the gene does
The CD59 protein functions as a membrane-bound complement regulatory molecule that specifically inhibits formation of the membrane attack complex. This complex, composed of complement proteins C5b through C9, creates pores in cell membranes that can lead to cell lysis and death. CD59 prevents this terminal step by binding to complement components C8 and C9, blocking their assembly into functional pores.
The protein is attached to the outer leaflet of cell membranes via a glycosylphosphatidylinositol anchor, allowing it to concentrate at sites where complement activation might occur. This strategic positioning enables CD59 to provide immediate protection across many cell types, including erythrocytes, leucocytes, endothelial cells, and neurons. By restricting complement activity to appropriate targets such as pathogens whilst sparing host cells, CD59 maintains the delicate balance between immune defence and self-tolerance.
Evidence suggests that CD59 expression levels can vary between tissues and may be modulated in response to inflammatory signals, providing additional layers of immune regulation.
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Chromosome location
CD59 is located on the short arm of chromosome 11 at position 13, designated 11p13. The genomic sequence spans approximately 25 kilobases and contains multiple exons that encode the mature protein and its signal peptide. This chromosomal region contains several other genes involved in immune function and metabolic regulation, though the specific clustering does not appear to reflect coordinated regulatory control.
Protein structure
The CD59 protein consists of 128 amino acids, including a signal peptide that is cleaved during processing. The mature form contains a UPAR/Ly6 domain spanning amino acids 26 to 108, which represents the functional core of the molecule. This domain adopts a compact three-dimensional structure stabilised by multiple disulphide bonds, creating binding surfaces that interact specifically with complement components C8 and C9. The glycosylphosphatidylinositol anchor attachment site is located near the C-terminus, securing the protein to the cell membrane in the correct orientation for complement inhibition.
Key variants
Pathogenic variants in CD59 are rare but clinically significant, typically resulting in complete or near-complete loss of protein function. Most disease-causing changes are nonsense mutations, frameshift deletions, or splice-site alterations that prevent production of functional protein. Because CD59 deficiency follows autosomal recessive inheritance, individuals must carry variants in both gene copies to manifest clinical features. Carrier status, with one functioning copy, generally does not cause symptoms.
Sample of pathogenic variants
4 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.146A>T | p.Asp49Val | Pathogenic | ★☆☆☆ | Primary CD59 deficiency |
c.266G>A | p.Cys89Tyr | Pathogenic | ★☆☆☆ | not provided |
c.123del | p.Val42fs | Pathogenic | - | Primary CD59 deficiency |
c.146del | p.Asp49fs | Pathogenic | - | Primary CD59 deficiency |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Complete CD59 deficiency leads to a spectrum of clinical features dominated by chronic haemolytic anaemia, in which red blood cells are destroyed prematurely by unregulated complement activation. Affected individuals may also develop neurological complications, including peripheral neuropathy and recurrent episodes of demyelination, reflecting complement-mediated damage to nerve cells. Some patients experience thrombotic events and recurrent infections due to broader immune dysregulation. The severity and specific manifestations can vary between individuals, possibly influenced by modifying genetic factors and environmental triggers that affect complement activation.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic CD59 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
CD59 appears on several NHS Genomic Medicine Service gene panels, reflecting its relevance to multiple clinical specialties. The gene holds green (high evidence) classification on panels for cytopenias and congenital anaemias, rare anaemia, and primary immunodeficiency or monogenic inflammatory bowel disease. It also features on hereditary neuropathy panels and was included in COVID-19 research efforts examining immune response variability. This broad panel representation underscores the diverse clinical presentations associated with CD59 deficiency and ensures appropriate consideration during genetic investigations for unexplained haemolysis, immune dysfunction, or neurological symptoms.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does CD59 deficiency cause?
Complete CD59 deficiency typically causes chronic haemolytic anaemia, in which red blood cells are destroyed prematurely by the complement system. Some individuals also develop neurological complications such as peripheral neuropathy or episodes of demyelination, and may experience blood clotting problems or recurrent infections.
How is CD59 deficiency inherited?
CD59 deficiency follows an autosomal recessive inheritance pattern. This means an individual must inherit pathogenic variants in both copies of the gene to develop the condition. People with one altered copy are carriers and typically do not show symptoms.
Is CD59 deficiency tested for on the NHS?
CD59 is included on multiple NHS Genomic Medicine Service panels for investigating unexplained anaemia, immune deficiency, and hereditary neuropathy. Testing may be considered when an individual presents with haemolytic anaemia or neurological symptoms that suggest complement-mediated disease, particularly if other common causes have been excluded.