HNF4G (Hepatocyte nuclear factor 4 gamma) is a NR2 Hepatocyte NF4-Like receptor. HNF4G is a pioneer factor that regulates a transcriptome of gastrointestinal lineage genes. Knockout studies have also revealed that it is involved in regulating energy expenditure, locomotor activity and food intake. It is structurally similar to HNF4 alpha and they are co-expressed in pancreatic islets. It is upregulated in some cancers, including bladder, prostate and lung cancer. In a small subclass of prostate cancers, the gastrointestinal regulatory profile of HNF4G is co-opted by tumor cells as part of therapy resistance. In lung cancers that overexpress HNF4G, expression correlates with tumor size and poor prognosis and it is thought to promote tumor cell proliferation. In immunohistochemistry, HNF4G has selective nuclear positivity in small intestine, and potentially also in the pancreas, liver, gallbladder kidney, and testis. References: Oncotarget. 2018 Apr 6; 9(26): 18018–18028, PMID: 29719587; Cancer Cell. 2017 Dec 11;32(6):792-806.e7, PMID: 29153843