Grid2ip, also known as glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein, is a Purkinje fiber postsynaptic scaffold protein. It is involved in several signal transduction pathways in the nervous system. As a Formin-homology protein without the FDD domain, it may play a role in cell polarity control through actin structure assembly [2].

In colorectal cancer (CRC), Grid2ip is upregulated. High expression of Grid2ip inhibits the invasion of tumor-associated immune cells, leading to a lower immune score and is associated with poor prognosis in different clinical subgroups. The subgroup with high Grid2ip expression is less sensitive to gemcitabine, suggesting Grid2ip could be a biomarker for CRC prognosis and a potential therapy target [1]. In the context of hemophilia A, low-frequency variants within Grid2ip are significantly associated with the development of inhibitors to replacement factor VIII, implicating an unrecognized role of this gene in autoimmunity [3]. Also, in a case of a child with autism, a 7p22.1 microduplication including the Grid2ip gene was detected, and the patient presented with features similar to previously reported cases with 7p22 duplication [4].

In conclusion, Grid2ip has important functions in the nervous system and is involved in multiple disease processes. Its role in CRC, hemophilia A, and potentially in autism-related chromosomal duplications, as revealed through these studies, provides valuable insights into the molecular mechanisms of these diseases. Understanding Grid2ip may offer new directions for disease diagnosis, prognosis prediction, and treatment development.

References:

1. Zhao, Jiajing, Quan, Jiazheng, Chen, Weilin, Xie, Xiaojun. 2023. Grid2 interacting protein is a potential biomarker related to immune infiltration in colorectal cancer. In European journal of medical research, 28, 511. doi:10.1186/s40001-023-01468-x. https://pubmed.ncbi.nlm.nih.gov/37964339/

2. Katoh, Masuko, Katoh, Masaru. . Identification and characterization of human GRID2IP gene and rat Grid2ip gene in silico. In International journal of molecular medicine, 12, 1015-9. doi:. https://pubmed.ncbi.nlm.nih.gov/14612983/

3. Lessard, Samuel, He, Chunla, Rajpal, Deepak K, Harris, Tim, Dumont, Jennifer. 2022. Genome-Wide Association Study and Gene-Based Analysis of Participants With Hemophilia A and Inhibitors in the My Life, Our Future Research Repository. In Frontiers in medicine, 9, 903838. doi:10.3389/fmed.2022.903838. https://pubmed.ncbi.nlm.nih.gov/35814780/

4. Goitia, Veronica, Oquendo, Marcial, Stratton, Robert. 2015. Case of 7p22.1 Microduplication Detected by Whole Genome Microarray (REVEAL) in Workup of Child Diagnosed with Autism. In Case reports in genetics, 2015, 212436. doi:10.1155/2015/212436. https://pubmed.ncbi.nlm.nih.gov/25893121/