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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CD46
CD46 molecule
Chromosome 1 Β· 1q32.2
NCBI Gene: 4179Ensembl: ENSG00000117335.21HGNC: HGNC:6953UniProt: A0A8Q3WLA6
255PubMed Papers
21Diseases
0Drugs
71Pathogenic Variants
FUNCTIONAL ROLE
Receptor
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
extracellular exosomeplasma membranecadherin bindingprotein sequestering activityatypical hemolytic-uremic syndrome with MCP/CD46 anomalyatypical hemolytic-uremic syndromecomplement deficiencydegeneration of macula and posterior pole
✦AI Summary

CD46 (membrane cofactor protein) is a ubiquitously expressed complement regulatory protein that serves multiple critical biological functions. As a primary function, CD46 acts as a cofactor for factor I-mediated inactivation of complement components C3b and C4b, protecting host cells from complement-mediated damage 1. Beyond complement regulation, CD46 modulates T cell immunity through positive regulation of T cell proliferation, regulatory T cell differentiation, and memory T cell formation [GO annotations]. Structurally, CD46 comprises four short consensus repeats (SCRs) in its extracellular region, with alternatively spliced isoforms generating tissue-specific variants 12. CD46 functions as a viral and bacterial entry receptor, earning designation as a "pathogen magnet" 3. Vaccine-adapted measles virus strains utilize CD46 as an alternative receptor through H protein amino acid substitutions 45. Additionally, CD46 facilitates entry of human cytomegalovirus in trophoblasts and certain epithelial cells 6, mediates human herpesvirus-6A infection through gQ1/gQ2 glycoproteins 7, and serves as a receptor for human adenovirus 26 via hexon protein binding 8. Clinically, CD46 dysfunction associates with atypical hemolytic uremic syndrome type 2. Recently, elevated CD46 expression correlates with malignant transformation and metastatic potential, positioning it as a cancer therapeutic target 3.

Sources cited
1
CD46 structure, isoforms, complement regulatory function (C3b/C4b inactivation), and tissue distribution
PMID: 10605818
2
Vaccine-adapted measles virus uses CD46 as alternate receptor through H protein substitutions
PMID: 19198560
3
CD46 established as measles virus cell entry receptor; binding inhibited by anti-CD46 antibodies
PMID: 19198561
4
CD46 facilitates human cytomegalovirus entry in trophoblasts and epithelial cells
PMID: 31221976
5
HHV-6A gQ1 and gQ2 glycoproteins critical for CD46 binding and infection
PMID: 24215487
6
Human adenovirus 26 uses CD46 for infection via hexon protein; role varies by administration route
PMID: 34787457
7
CD46 structural characteristics with four SCRs and role as pathogen receptor
PMID: 37515111
8
CD46 roles in T cell modulation, autophagy, cancer biology, and as pathogen entry factor for multiple bacteria and viruses
PMID: 40309774
Disease Associationsβ“˜21
atypical hemolytic-uremic syndrome with MCP/CD46 anomalyOpen Targets
0.78Strong
atypical hemolytic-uremic syndromeOpen Targets
0.72Strong
complement deficiencyOpen Targets
0.46Moderate
degeneration of macula and posterior poleOpen Targets
0.38Weak
macular degenerationOpen Targets
0.38Weak
retinopathyOpen Targets
0.37Weak
atypical hemolytic uremic syndrome with complement gene abnormalityOpen Targets
0.37Weak
thrombotic microangiopathyOpen Targets
0.34Weak
retinal degenerationOpen Targets
0.33Weak
age-related macular degenerationOpen Targets
0.32Weak
adolescent idiopathic scoliosisOpen Targets
0.31Weak
retinoschisisOpen Targets
0.30Weak
chondromalaciaOpen Targets
0.30Weak
MMR-related febrile seizuresOpen Targets
0.28Weak
keratoconusOpen Targets
0.27Weak
Febrile seizure (within the age range of 3 months to 6 years)Open Targets
0.25Weak
response to vaccineOpen Targets
0.23Weak
Abnormality of the skeletal systemOpen Targets
0.19Weak
intelligenceOpen Targets
0.16Weak
Alzheimer diseaseOpen Targets
0.15Weak
Hemolytic uremic syndrome, atypical, 2UniProt
Pathogenic Variants71
NM_172351.3(CD46):c.286+2T>GPathogenic
Atypical hemolytic-uremic syndrome|Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly|not provided|Familial Atypical Hemolytic-Uremic Syndrome
β˜…β˜…β˜†β˜†2026
NM_172351.3(CD46):c.287-2A>GPathogenic
not provided|Thrombotic microangiopathy|Familial Atypical Hemolytic-Uremic Syndrome|Atypical hemolytic-uremic syndrome|Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly
β˜…β˜…β˜†β˜†2026
NM_172351.3(CD46):c.286+1G>CPathogenic
not provided|Atypical hemolytic-uremic syndrome|CD46-related atypical hemolytic uremic syndrome
β˜…β˜…β˜†β˜†2025
NM_172351.3(CD46):c.685C>T (p.Arg229Ter)Pathogenic
Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly|not provided|Atypical hemolytic-uremic syndrome|Autosomal dominant and autosomal recessive CD46-related disorders
β˜…β˜…β˜†β˜†2025β†’ Residue 229
NM_172351.3(CD46):c.175C>T (p.Arg59Ter)Pathogenic
Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly|not provided|Atypical hemolytic-uremic syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 59
NM_172351.3(CD46):c.820_821del (p.Ser274fs)Pathogenic
not provided|Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly|Atypical hemolytic-uremic syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 274
NM_172351.3(CD46):c.350_351dup (p.Glu118fs)Pathogenic
Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly|Atypical hemolytic-uremic syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 118
NM_172351.3(CD46):c.828G>A (p.Trp276Ter)Pathogenic
Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly|Atypical hemolytic-uremic syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 276
NM_172351.3(CD46):c.350dup (p.Tyr117Ter)Pathogenic
Atypical hemolytic-uremic syndrome|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 117
NM_172351.3(CD46):c.381T>A (p.Cys127Ter)Pathogenic
Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly|Atypical hemolytic-uremic syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 127
NM_172351.3(CD46):c.857-1G>ALikely pathogenic
Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly|not provided
β˜…β˜…β˜†β˜†2025
NM_172351.3(CD46):c.257G>A (p.Trp86Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 86
NM_172351.3(CD46):c.857-174A>CLikely pathogenic
not provided|CD46-related disorder
β˜…β˜…β˜†β˜†2023
NM_172351.3(CD46):c.350del (p.Tyr117fs)Pathogenic
Atypical hemolytic-uremic syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 117
NM_172351.3(CD46):c.475+1G>ALikely pathogenic
Atypical hemolytic-uremic syndrome
β˜…β˜†β˜†β˜†2025
NM_172351.3(CD46):c.2T>A (p.Met1Lys)Likely pathogenic
Atypical hemolytic-uremic syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 1
NM_172351.3(CD46):c.295T>C (p.Cys99Arg)Likely pathogenic
Atypical hemolytic-uremic syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 99
NM_172351.3(CD46):c.493C>T (p.Pro165Ser)Likely pathogenic
Atypical hemolytic-uremic syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 165
NM_172351.3(CD46):c.800_801del (p.Thr267fs)Pathogenic
Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly|Atypical hemolytic-uremic syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 267
NM_172351.3(CD46):c.98-1G>CPathogenic
Atypical hemolytic-uremic syndrome with MCP/CD46 anomaly|Atypical hemolytic-uremic syndrome
β˜…β˜†β˜†β˜†2025
View on ClinVar β†—
Related Genes
CFBProtein interaction100%SERPING1Protein interaction100%C2Protein interaction100%C3Protein interaction100%C4AProtein interaction100%C4BProtein interaction100%
Tissue Expression6 tissues
Lung
100%
Liver
68%
Bone Marrow
66%
Ovary
65%
Heart
63%
Brain
25%
Gene Interaction Network
Click a node to explore
CD46CFBSERPING1C2C3C4AC4B
PROTEIN STRUCTURE
Preparing viewer…
PDB5FO8 Β· 2.40 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.76LoF Tolerant
pLIβ“˜
0.04Tolerant
Observed/Expected LoF0.48 [0.31–0.76]
RankingsWhere CD46 stands among ~20K protein-coding genes
  • #1,507of 20,598
    Most Researched255 Β· top 10%
  • #1,022of 5,498
    Most Pathogenic Variants71 Β· top quartile
  • #6,124of 17,882
    Most Constrained (LOEUF)0.76
Genes detectedCD46
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Measles virus receptors.
PMID: 19198560
Curr Top Microbiol Immunol Β· 2009
1.00
2
CD46 facilitates entry and dissemination of human cytomegalovirus.
PMID: 31221976
Nat Commun Β· 2019
0.90
3
Measles virus and CD46.
PMID: 19198561
Curr Top Microbiol Immunol Β· 2009
0.80
4
The multiverse of CD46 and oncologic interactions.
PMID: 40309774
J Clin Invest Β· 2025
0.70
5
CD46 Is a Protein Receptor for Human Adenovirus Type 64.
PMID: 39772136
Viruses Β· 2024
0.60