Arfgef3, also known as Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3), is involved in guanine nucleotide-exchange factor activity, which is crucial for regulating the function of ADP-ribosylation factor (ARF) proteins. These proteins play roles in intracellular vesicular trafficking and membrane-associated protein sorting pathways [7-10].

In a study on systemic lupus erythematosus (SLE), ARFGEF3 was among the 7 upregulated differentially expressed genes (DEGs) in severe SLE (sSLE) compared to mild SLE (mSLE), suggesting its potential role in SLE severity [1]. In the Bull Terrier, a missense variant in ARFGEF3 (chr1:30793904G>A, XP_038382065.1 p.V243I) significantly reduces breed-representative height, indicating its possible involvement in body size regulation [2]. In a study on intellectual disability (ID), exome sequencing revealed de novo and recessive variants in ARFGEF3, highlighting it as a potential candidate gene for ID [3]. A genome-wide association study identified a variant in ARFGEF3 (rs143276236) associated with metformin glycemic response in African American patients with type 2 diabetes [4]. In a mouse model of excessive female aggression, Arfgef3 was among the genes with altered expression in the prefrontal cortex of stressed mice with partial genetic inactivation of tryptophan hydroxylase-2, indicating its possible link to aggression-related behaviors [5].

In conclusion, Arfgef3 is involved in multiple biological processes. Through studies in various genetic models, its role in diseases such as SLE, ID, and type 2 diabetes, as well as in body size regulation and aggression-related behaviors, has been uncovered. These findings contribute to understanding the underlying molecular mechanisms of these conditions and potentially developing targeted therapies.

References:

1. Zhang, Xiaojing, Zhang, Jiali, Pan, Zhaobing, Zhou, Fusheng, Wen, Leilei. 2023. Transcriptome sequencing reveals novel molecular features of SLE severity. In Frontiers in genetics, 14, 1121359. doi:10.3389/fgene.2023.1121359. https://pubmed.ncbi.nlm.nih.gov/37554401/

2. Wade, Claire M. . Insights into the genetics of body size in the Bull Terrier. In Animal genetics, 56, e70000. doi:10.1111/age.70000. https://pubmed.ncbi.nlm.nih.gov/39871672/

3. Anazi, S, Maddirevula, S, Faqeih, E, Shaheen, R, Alkuraya, F S. 2016. Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield. In Molecular psychiatry, 22, 615-624. doi:10.1038/mp.2016.113. https://pubmed.ncbi.nlm.nih.gov/27431290/

4. Wu, Baojun, Yee, Sook Wah, Xiao, Shujie, Giacomini, Kathleen M, Williams, L Keoki. . Genome-Wide Association Study Identifies Pharmacogenomic Variants Associated With Metformin Glycemic Response in African American Patients With Type 2 Diabetes. In Diabetes care, 47, 208-215. doi:10.2337/dc22-2494. https://pubmed.ncbi.nlm.nih.gov/37639712/

5. Strekalova, Tatyana, Moskvin, Oleg, Jain, Aayushi Y, Lesch, Klaus-Peter, Lim, Lee Wei. 2023. Molecular signature of excessive female aggression: study of stressed mice with genetic inactivation of neuronal serotonin synthesis. In Journal of neural transmission (Vienna, Austria : 1996), 130, 1113-1132. doi:10.1007/s00702-023-02677-8. https://pubmed.ncbi.nlm.nih.gov/37542675/