CD81: A Key Tetraspanin in Immunity, Viral Entry, and Cancer
Explore the CD81 gene, its protein functions, associated diseases, expression patterns, and clinical significance.
Gene Information Card
| Symbol | CD81 |
|---|---|
| Full Name | CD81 molecule |
| Gene Type | protein-coding |
| Chromosomal Location | 11p15.5 |
| NCBI Gene ID | 975 ncbi.nlm.nih.gov/gene/975 |
| Ensembl ID | ENSG00000124762 |
| UniProt ID | P60033 |
| OMIM ID | 186845 |
| HGNC ID | 1700 |
| Aliases | TAPA1, S5.7, CVID6, TSPAN28 |
Description
CD81 is a member of the tetraspanin family, characterized by four transmembrane domains. It is a cell surface glycoprotein involved in a wide range of cellular processes including cell adhesion, motility, signaling, and immune responses. CD81 is a component of the CD19/CD21 signal transduction complex on B cells, playing a critical role in B cell activation and antibody production. It also serves as a receptor for the hepatitis C virus (HCV) envelope protein E2, facilitating viral entry into hepatocytes. Additionally, CD81 is implicated in cancer progression, where its expression can modulate tumor cell invasion and metastasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency, common variable, 6 (CVID6) | Loss-of-function mutations in CD81 lead to defective B cell signaling and antibody production, causing immunodeficiency. | OMIM, ClinVar |
| Hepatitis C virus infection | CD81 acts as a host receptor for HCV E2 glycoprotein, mediating viral entry into hepatocytes. Polymorphisms may influence susceptibility. | NCBI, UniProt |
| Cancer (various types) | CD81 expression is altered in several cancers, affecting tumor cell adhesion, migration, and invasion. It can promote or suppress tumor progression depending on context. | COSMIC, PubMed |
| Schistosomiasis | CD81 is involved in the host immune response to Schistosoma infection, potentially influencing granuloma formation. | UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | High | High |
| Spleen | High | High |
| Lymph node | High | High |
| Bone marrow | Medium | Medium |
| Liver | Medium | Medium |
| Lung | Medium | Medium |
| Kidney | Low | Low |
| Brain | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| B cells | High | Strong expression on mature B cells |
| T cells | Medium | Expressed on subsets, involved in T cell activation |
| Hepatocytes | Medium | Key for HCV entry |
| Endothelial cells | Medium | Expressed on vascular endothelium |
| HeLa (cervical cancer) | High | Overexpressed in many cancer cell lines |
| MCF7 (breast cancer) | Medium | Expression varies with subtype |
Data source:Human Protein Atlas(proteinatlas.org)
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.561C>A (p.Cys187Ter) | Nonsense | Rare | Loss of function, causes CVID6 |
| c.227T>C (p.Leu76Pro) | Missense | Rare | Impaired protein trafficking, associated with CVID6 |
| c.458A>G (p.Asn153Ser) | Missense | Low frequency | Potential impact on HCV entry |
| c.1A>G (p.Met1Val) | Start codon loss | Rare | Loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CD81, such as nonsense or frameshift variants, result in truncated or absent protein, leading to defective B cell signaling and immunodeficiency (CVID6).
Gain of Function (GOF)
No clear gain-of-function mutations have been documented for CD81. Overexpression in certain cancers may be considered a gain-of-function at the expression level, but not due to specific mutations.
Dominant Negative (DN)
Dominant-negative effects have not been reported for CD81 mutations. The tetraspanin functions as part of complexes, but most pathogenic mutations are recessive.
View complete mutation data:
Gene Ontology (GO)
| • protein binding | • identical protein binding |
| • receptor binding | • cell surface receptor signaling pathway |
| • cell adhesion | • cell-cell signaling |
| • immune response | • B cell activation |
| • viral entry into host cell | • positive regulation of cell proliferation |
| • negative regulation of cell migration |
Pathways
• B cell receptor signaling pathway
• Hepatitis C virus entry pathway
• Integrin signaling pathway
• Tetraspanin-enriched microdomain organization
Protein Summary
CD81 is a 236-amino acid tetraspanin protein with four transmembrane domains, a small extracellular loop (SEL) and a large extracellular loop (LEL). The LEL is critical for interactions with viral glycoproteins and other cellular proteins. CD81 forms complexes with integrins, other tetraspanins, and signaling molecules, organizing membrane microdomains that facilitate signal transduction. It is heavily glycosylated and palmitoylated, which influences its localization and function. CD81 is essential for B cell function, as it partners with CD19 and CD21 to lower the threshold for B cell activation. In the liver, CD81 is a key entry factor for HCV, binding to the E2 glycoprotein and initiating clathrin-mediated endocytosis. Its role in cancer is context-dependent, with studies showing both tumor-promoting and tumor-suppressive effects depending on the tissue and microenvironment.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CD81 Knockout HEK293 Cell Line | EDJ-KQ1046 | Human | 975 | Details Get a Quote |
| CD81 Knockout A-549 Cell Line | EDJ-KQ20155 | Human | 975 | Details Get a Quote |
| CD81 Knockout HCT 116 Cell Line | EDJ-KQ20156 | Human | 975 | Details Get a Quote |
| CD81 Knockout HeLa Cell Line | EDJ-KQ20157 | Human | 975 | Details Get a Quote |
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