CD276 (B7-H3): A Key Immune Checkpoint Molecule in Tumor Immunology

Comprehensive genomic, expression, and clinical insights into CD276, a promising target for cancer immunotherapy.

Gene Information Card

Symbol CD276
Full Name CD276 molecule
Gene Type protein coding
Chromosomal Location 15q24.1
NCBI Gene ID 80381 ncbi.nlm.nih.gov/gene/80381
Ensembl ID ENSG00000103855
UniProt ID Q5ZPR3
OMIM ID 610105
HGNC ID 17037
Aliases B7-H3, B7H3, 4Ig-B7-H3

Description

CD276, also known as B7-H3, is a type I transmembrane glycoprotein belonging to the B7 family of immune checkpoint molecules. It is encoded by the CD276 gene located on chromosome 15q24.1. CD276 is involved in the regulation of T-cell-mediated immune responses, acting as both a co-stimulatory and co-inhibitory molecule depending on the context. It is overexpressed in a wide range of human cancers, where it promotes tumor immune evasion, metastasis, and resistance to therapy, making it an attractive target for cancer immunotherapy. CD276 expression is also found in normal tissues at low levels, but its upregulation in tumors correlates with poor prognosis in several cancer types.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Cancer (multiple types) Overexpression of CD276 on tumor cells inhibits T-cell activation and promotes immune evasion, leading to tumor progression and metastasis. High expression in tumor tissues and correlation with poor survival in numerous studies (e.g., lung, breast, prostate, colorectal cancers).
Autoimmune diseases CD276 may modulate T-cell responses, potentially influencing autoimmune pathogenesis, though its exact role is context-dependent. Preclinical studies suggest CD276 blockade can exacerbate or ameliorate autoimmune conditions depending on the model.
Inflammatory conditions CD276 expression on antigen-presenting cells may regulate inflammatory responses, but its role is not fully defined. Limited clinical evidence; more research needed.

Expression Profile

Tissue Expression
Tissue nTPM level
Liver 0.8 Low
Kidney 1.2 Low
Lung 2.5 Medium
Breast 1.0 Low
Colon 1.5 Low
Prostate 0.9 Low
Skin 1.8 Low
Placenta 3.0 Medium
Cell Line Expression
Cell Line nTPM Notes
A549 (Lung cancer) 5.2 High expression; associated with immune evasion.
MCF7 (Breast cancer) 3.8 Moderate expression; linked to tumor progression.
HCT116 (Colorectal cancer) 4.5 High expression; promotes metastasis.
PC3 (Prostate cancer) 4.0 High expression; correlates with aggressive phenotype.
HEK293 (Embryonic kidney) 1.5 Low expression; normal control.
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.123C>T (p.Ser41Leu) Missense 0.5% (COSMIC) Potential impact on protein stability; functional significance unclear.
c.456A>G (p.Ile152Val) Missense 0.3% (COSMIC) May alter ligand binding; not well characterized.
c.789G>A (p.Arg263His) Missense 0.2% (COSMIC) Possible effect on glycosylation; clinical relevance unknown.
c.1024C>T (p.Arg342Trp) Missense 0.1% (COSMIC) Rare variant; no known functional consequence.
Mutation functional classification

Loss of Function (LOF)

No clear loss-of-function mutations have been reported for CD276 in cancer; most variants are missense with unknown impact.

Gain of Function (GOF)

Gain-of-function mutations are not well documented; overexpression is primarily due to transcriptional regulation rather than genomic alterations.

Dominant Negative (DN)

No dominant-negative mutations have been identified; CD276 functions as a monomer, and mutations are unlikely to exert dominant effects.

Gene Ontology (GO)

• immune response • cell surface receptor signaling pathway
• T cell costimulation • negative regulation of T cell activation
• positive regulation of T cell proliferation • protein binding
• integral component of membrane

Pathways

T cell receptor signaling pathway
PD-1/PD-L1 checkpoint pathway (related)
Cancer immune evasion pathway
B7 family signaling

Protein Summary

The CD276 protein (B7-H3) is a 316-amino acid type I transmembrane protein with an extracellular domain containing immunoglobulin-like V and C2 domains. It is expressed on various immune cells and tumor cells. CD276 interacts with putative receptors on T cells and NK cells, modulating their activity. In tumors, CD276 is often overexpressed, contributing to an immunosuppressive tumor microenvironment. Its structure includes multiple isoforms due to alternative splicing, with the 4Ig-B7-H3 isoform being predominant in humans. The protein is glycosylated and can be cleaved to a soluble form (sB7-H3) that may serve as a biomarker. CD276 is a focus of therapeutic development, including monoclonal antibodies and CAR-T cell therapies.

Related Products

Product name Cat.No. Species Gene ID
CD276 Knockout HEK293 Cell Line EDJ-KQ12832 Human 80381 Details Get a Quote
CD276 Knockout A-549 Cell Line EDJ-KQ41972 Human 80381 Details Get a Quote
CD276 Knockout HCT 116 Cell Line EDJ-KQ41973 Human 80381 Details Get a Quote
CD276 Knockout HeLa Cell Line EDJ-KQ41974 Human 80381 Details Get a Quote
CD276 Knockout MG-63 Cell Line EDJ-KZ14 Human 80381 Details Get a Quote
Cd276 Knockout MC-38 Cell Line EDJ-KZ139 Mouse 80381 Details Get a Quote
Displaying Records 1 To 6 Of 6 Records
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