Brefeldin A-inhibited guanine nucleotide-exchange protein 3

ARFGEF3 (Brefeldin A-inhibited guanine nucleotide-exchange protein 3) is a large guanine nucleotide-exchange factor that regulates insulin and glucagon granule biogenesis in pancreatic beta and alpha cells, respectively (UniProt: Q5TH69). The protein also modulates nuclear translocation of PHB2 and may influence estrogen receptor alpha transcriptional activity in breast cancer cells. It is a 2177-amino acid protein with a molecular mass of approximately 240.7 kDa.

ARFGEF3 is primarily associated with glucose homeostasis and pancreatic endocrine function. UniProt records no primary disease associations, though its role in systemic metabolic regulation suggests potential relevance to metabolic disorders.

In Alzheimer's disease, ARFGEF3 is downregulated in post-mortem human AD brain tissue compared to age-matched controls (mean log2FC: −0.417) as detected by TMT-labeled quantitative proteomics across four subcellular fractions (Chaparral AD proteomics). The functional significance of this downregulation in the context of AD neurodegeneration remains to be determined.