TNFRSF21 Gene (DR6): Function, Expression, Disease Associations, and Mutations

TNFRSF21 (Tumor Necrosis Factor Receptor Superfamily Member 21), also known as Death Receptor 6 (DR6), is a type I transmembrane receptor belonging to the TNF receptor superfamily. It is characterized by four extracellular cysteine-rich domains and a cytoplasmic death domain. DR6 is widely expressed in various tissues, with particularly high levels in the brain and lymphoid organs. It plays a dual role in cell signaling: it can induce apoptosis via the extrinsic pathway and also modulate inflammation and immune responses. In the nervous system, DR6 is involved in axonal pruning and degeneration, and has been implicated in Alzheimer's disease pathology. Additionally, TNFRSF21 has been studied in the context of cancer, where its expression can influence tumor progression and immune evasion.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• TNF signaling pathway (KEGG hsa04668)

• Apoptosis (KEGG hsa04210)

• Cytokine-cytokine receptor interaction (KEGG hsa04060)

• NF-kappa B signaling pathway (KEGG hsa04064)

The TNFRSF21 protein (DR6) is a 655-amino acid type I transmembrane receptor. It contains four cysteine-rich domains (CRDs) in the extracellular region and a death domain in the cytoplasmic tail. DR6 is synthesized as a precursor that is cleaved to form the mature receptor. It interacts with ligands such as APP (amyloid precursor protein) and possibly other TNF family members. Upon ligand binding, DR6 recruits signaling complexes that can activate caspases (leading to apoptosis) or NF-kB (leading to inflammation). In neurons, DR6 signaling is crucial for axonal pruning and degeneration. The protein is post-translationally modified by N-glycosylation, which may affect its stability and function.