Size of protein-coding genes. The size of protein-coding genes within the human genome shows enormous variability. For example, the gene for histone H1a (HIST1HIA) is relatively small and simple, lacking introns and encoding an 781 nucleotide-long mRNA that produces a 215 amino acid protein from its 648 nucleotide open reading frame. Dystrophin (DMD) was the largest protein-coding gene in the 2001 human reference genome, spanning a total of 2.2 million nucleotides, while more recent systematic meta-analysis of updated human genome data identified an even larger protein-coding gene, "RBFOX1" (RNA binding protein, fox-1 homolog 1), spanning a total of 2.47 million nucleotides. Titin (TTN) has the longest coding sequence (114,414 nucleotides), the largest number of exons (363), and the longest single exon (17,106 nucleotides). As estimated based on a curated set of protein-coding genes over the whole genome, the median size is 26,288 nucleotides (mean = 66,577), the median exon size, 133 nucleotides (mean = 309), the median number of exons, 8 (mean = 11), and the median encoded protein is 425 amino acids (mean = 553) in length.