In this study, we describe the identification and cloning of a novel member of the nuclear receptor superfamily. This orphan receptor, referred to as RORγ, belongs to the ROR/RZR subfamily. The open reading frame of RORγ encodes a protein of 560 amino acid residues with a predicted molecular mass of 63 kD. The amino acid sequence of RORγ exhibits a 50 and 51% identity with those of RORα/RZRα and RZRβ, respectively, whereas the DNA-binding domains were 89% identical. RORγ was localized on human chromosome 1. Northern blot analysis using RNA from multiple tissues indicated that RORγ is expressed in several tissues but is most highly expressed in skeletal muscle. © 1994 Academic Press. All rights reserved.