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.

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 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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