Arhgef28, also known as Rgnef or p190RhoGEF, is a guanine nucleotide exchange factor. It is involved in multiple cellular processes, such as promoting colon carcinoma cell motility and tumor progression via interaction with focal adhesion kinase (FAK) [3]. It has also been suggested to be an effector of Gα13 signaling [3].

Mutations in Arhgef28 have been associated with several diseases. In a Chinese amyotrophic lateral sclerosis (ALS) cohort, the intron 6, + 1 del G (GT>TT) mutation of the Arhgef28 gene was found in 0.52% of ALS patients, with mutation-positive patients showing different clinical features from previous reports [1]. Sequencing of the entire coding sequence of Arhgef28 in Chinese sporadic ALS cases identified rare coding variants potentially contributing to ALS, with carriers of rare deleterious variants having a marginally younger age at onset [2]. In a familial non-medullary thyroid cancer kindred, variations in Arhgef28 were associated with the disease, and its protein-protein interactions suggest a predisposition to papillary thyroid carcinoma [4].

In conclusion, Arhgef28 plays important roles in cell motility-related processes and is associated with diseases like ALS and non-medullary thyroid cancer. Studies on Arhgef28 contribute to understanding the genetic mechanisms underlying these diseases, potentially offering insights for diagnosis and treatment. Although no KO/CKO mouse models were mentioned in the references, the genetic studies on human patients have revealed its significance in disease-related processes.

References:

1. Ma, Yan, Tang, Lu, Chen, Lu, Zhang, Huagang, Fan, Dongsheng. 2014. ARHGEF28 gene exon 6/intron 6 junction mutations in Chinese amyotrophic lateral sclerosis cohort. In Amyotrophic lateral sclerosis & frontotemporal degeneration, 15, 309-11. doi:10.3109/21678421.2014.896926. https://pubmed.ncbi.nlm.nih.gov/24712971/

2. Song, Yang, Lin, Feng, Ye, Cheng-Hui, Xu, Yanming, Wang, Chaodong. 2019. Rare, low-frequency and common coding variants of ARHGEF28 gene and their association with sporadic amyotrophic lateral sclerosis. In Neurobiology of aging, 87, 138.e1-138.e6. doi:10.1016/j.neurobiolaging.2019.02.021. https://pubmed.ncbi.nlm.nih.gov/31060816/

3. Masià-Balagué, Miriam, Izquierdo, Ismael, Garrido, Georgina, Gigoux, Véronique, Aragay, Anna M. 2015. Gastrin-stimulated Gα13 Activation of Rgnef Protein (ArhGEF28) in DLD-1 Colon Carcinoma Cells. In The Journal of biological chemistry, 290, 15197-209. doi:10.1074/jbc.M114.628164. https://pubmed.ncbi.nlm.nih.gov/25922072/

4. Majdalani, Pierre, Yoel, Uri, Nasasra, Tayseer, Hershkovitz, Eli, Parvari, Ruti. 2023. Novel Susceptibility Genes Drive Familial Non-Medullary Thyroid Cancer in a Large Consanguineous Kindred. In International journal of molecular sciences, 24, . doi:10.3390/ijms24098233. https://pubmed.ncbi.nlm.nih.gov/37175943/