GRM1, encoding metabotropic glutamate receptor 1 (mGluR1), is pivotal in slow excitatory postsynaptic conductance, synapse formation, synaptic plasticity, and motor control [4]. It is mainly expressed in the brain, especially highly in the cerebellum, and is involved in glutamate signaling pathways [4,6].

In chondromyxoid fibroma (CMF), GRM1 is frequently rearranged. These rearrangements place GRM1 under the control of a constitutively active promoter, leading to increased gene expression. GRM1 immunohistochemistry can distinguish CMF from its histologic mimics, as it is positive in 97% of CMF specimens but negative in mimics [1,5,6]. In blue nevi and related melanomas, GRM1 gene fusions can act as an alternative oncogenic driver, mutually exclusive of classical canonical mutations [2]. Also, GRM1 has been associated with attention-deficit/hyperactive disorder (ADHD), and its mutations are related to congenital cerebellar ataxia and schizophrenia [3,4,7].

In summary, GRM1 plays a crucial role in various biological and disease-related processes. Studies on its genetic alterations, such as in CMF, blue nevi-related melanomas, and neurological disorders, have enhanced our understanding of the molecular mechanisms underlying these diseases. The association of GRM1 with different diseases suggests its potential as a diagnostic or therapeutic target in multiple disease areas.

References:

1. Toland, Angus M S, Lam, Suk Wai, Varma, Sushama, Bovée, Judith V M G, Charville, Gregory W. 2022. GRM1 Immunohistochemistry Distinguishes Chondromyxoid Fibroma From its Histologic Mimics. In The American journal of surgical pathology, 46, 1407-1414. doi:10.1097/PAS.0000000000001921. https://pubmed.ncbi.nlm.nih.gov/35650682/

2. Kervarrec, Thibault, Lo Bello, Giuseppe, Pissaloux, Daniel, Houlier, Aurélie, de la Fouchardière, Arnaud. 2023. GRM1 Gene Fusions as an Alternative Molecular Driver in Blue Nevi and Related Melanomas. In Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 36, 100264. doi:10.1016/j.modpat.2023.100264. https://pubmed.ncbi.nlm.nih.gov/37391170/

3. Kessi, Miriam, Duan, Haolin, Xiong, Juan, Peng, Jing, Yin, Fei. 2022. Attention-deficit/hyperactive disorder updates. In Frontiers in molecular neuroscience, 15, 925049. doi:10.3389/fnmol.2022.925049. https://pubmed.ncbi.nlm.nih.gov/36211978/

4. Protasova, Maria S, Andreeva, Tatiana V, Klyushnikov, Sergey A, Illarioshkin, Sergey N, Rogaev, Evgeny I. 2023. Genetic Variant in GRM1 Underlies Congenital Cerebellar Ataxia with No Obvious Intellectual Disability. In International journal of molecular sciences, 24, . doi:10.3390/ijms24021551. https://pubmed.ncbi.nlm.nih.gov/36675067/

5. Machado, Isidro, Zhang, Yanming, Hameed, Meera, Bilsky, Mark H, Linos, Konstantinos. 2024. GRM1-Rearranged Chondromyxoid Fibroma With FGF23 Expression: A Potential Pitfall in Small Biopsies. In International journal of surgical pathology, 32, 1500-1507. doi:10.1177/10668969241229345. https://pubmed.ncbi.nlm.nih.gov/38303543/

6. Nord, Karolin H, Lilljebjörn, Henrik, Vezzi, Francesco, Hogendoorn, Pancras C W, Szuhai, Karoly. 2014. GRM1 is upregulated through gene fusion and promoter swapping in chondromyxoid fibroma. In Nature genetics, 46, 474-7. doi:10.1038/ng.2927. https://pubmed.ncbi.nlm.nih.gov/24658000/

7. Ayoub, Mohammed Akli, Angelicheva, Dora, Vile, David, Pfleger, Kevin D G, Kalaydjieva, Luba. 2012. Deleterious GRM1 mutations in schizophrenia. In PloS one, 7, e32849. doi:10.1371/journal.pone.0032849. https://pubmed.ncbi.nlm.nih.gov/22448230/