Germ cell nuclear factor (GCNF), a NR6 Germ Cell Nuclear Factor-Like Receptor, has been shown to affect gene expression in embryogenesis and spermatogenesis and is essential for embryonic survival and normal development. Loss of GCNF causes embryonic lethality and disrupts normal somitogenesis as well as neural-tube and axis formation. GCNF binds as a homodimer to the DR0 DNA response element and has been shown to regulate transcription of genes including protamines1 and 2 and Oct4. GCNF's repression function has been shown to be mediated by interaction with the co-repressors N-COR and SMRT in the absence of ligand. Three protein isoforms, GCNF-1, GCNF-2a, and GCNF-2b, have been documented in humans, and they are generated by differential usage of alternative splice acceptor sites of the fourth and seventh exons. GCNF-1, the longest isoform, has a distinct 5' UTR and contains 4 and 26 additional amino acids than the other two forms, respectively. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804