The human glucagon receptor-encoding gene is responsible for producing a receptor protein in the cell.  The gene is believed to be essential for natural human physiological function.  The receptor that the gene encodes for helps regulate the level of blood glucose by controlling the rate of hepatic glucose production and insulin secretion.  Therefore the gene encodes for an essential receptor protein that is important in human metabolism (OMIM).

    Menzel et al discovered the physical locus of the gene in 1994.  Menzel also identified 85% nucleotide and 91% amino acid identity with the rat sequence of the same gene (Menzel 1994).  Southern blot analysis of human DNA suggested a single locus of the glucagon receptor (GCGR) gene and in situ hybridization mapped the locus to the 17q25 band.  The gene is inherited by normal autosomal recessive inheritance from both parents.  The gene is physically located at the tip of the long arm of chromosome seventeen.  An illustration of the locus of the gene is shown in Figure 1 (OMIM).
 

    Analysis of the genomic sequence showed that the encoding region spans over 5.5 kb and is interrupted by 12 introns.  An experimental cDNA sequence of the GCGR gene contained a total of 2034 base pairs.  The experimental cDNA sequence contains 351 adenine, 681 cytosine, 625 guanine, and 377 thymine as its nucleotide composition.  This cDNA sequence of the gene derived from mRNA is illustrated in Figure 2 (OMIM).

    The product of the gene after transcription and translation is a 477 amino acid protein.  The protein is a seven transmembrane protein and is coupled to adenyl cyclase by G-proteins.  The unprocessed protein has a molecular weight of 54009 Daltons.  The domains that have been identified in the protein sequence and the point of carbohydrate addition and mutation have been listed and are illustrated in Figure 3 (SWISS-PROT).

    Currently there is only one polymorphic variant that is associated with any type of disease.  It has been reported that late onset noninsulin dependent diabetes mellitus (NIDDM) can be associated with a single heterozygous gly-to-ser missense mutation in the glucagon receptor gene.  The mutation that replaces glycine at residue 40 by serine results in a receptor that binds glucagon with a 3-fold lower affinity compared to the wild type receptor (OMIM).

    The GCGR gene could be called a typically normal gene with normal autosomal inheritance and very small amounts of detrimental mutations or variants.