GPR98

GPR98 (G Protein-Coupled Receptor 98), also known as VLGR1 (Very Large G Protein-Coupled Receptor 1), is a protein that in humans is encoded by the GPR98 gene. This gene is a member of the adhesion-GPCR family of receptors, which is a diverse group of large, non-classical G protein-coupled receptors (GPCRs) that play critical roles in a variety of physiological processes.

Function

GPR98 is involved in several key biological functions, including the regulation of cell adhesion, cell signaling, and possibly sensory perception. It is expressed in a wide range of tissues, with high levels in the central nervous system (CNS), kidney, and inner ear, suggesting its importance in neural, renal, and auditory functions. The protein is characterized by an extremely large extracellular domain, which is believed to interact with a variety of extracellular matrix proteins and other cell surface molecules, facilitating cell-cell and cell-matrix interactions.

Clinical Significance

Mutations in the GPR98 gene have been associated with Usher syndrome type 2C (USH2C), a condition characterized by hearing loss and retinitis pigmentosa, leading to progressive vision loss. Usher syndrome is the most common condition that affects both hearing and vision. The involvement of GPR98 in Usher syndrome highlights its role in the development and maintenance of the auditory and visual systems.

Additionally, due to its widespread expression and involvement in cell signaling pathways, GPR98 is being studied for its potential roles in other diseases, including certain types of cancer and neurodegenerative diseases. However, the full extent of its involvement in these conditions remains to be elucidated.

Genetic and Molecular Aspects

The GPR98 gene is located on the long (q) arm of chromosome 5 at position 14.3, spanning over 600 kilobases and comprising 90 exons, making it one of the largest genes in the human genome. The GPR98 protein is also one of the largest known GPCRs, with a mass of approximately 630 kDa. Its large size and complex structure suggest that it may interact with multiple ligands and participate in diverse signaling pathways.

Research Directions

Research on GPR98 is ongoing, with studies focusing on understanding its precise mechanisms of action, its role in disease, and its potential as a therapeutic target. Given its involvement in critical physiological processes and disease states, GPR98 represents a promising area for future drug development, particularly for conditions like Usher syndrome and potentially other sensory disorders.