The PrP gene, PRNP (NC_000020.11), has been localised to the short arm of chromosome 20 (20pter-12; 4686151-4701588)1-2. PRNP is a single-copy 16 Kb gene and contains two exons, separated by a 13 Kb intron. Exon 1 is non-coding and is thought to comprise the transcriptional initiation site. The open reading frame (ORF), encoding the PrP protein, is composed of 253 amino acids and located entirely within exon 2 (Figure 1)3. The 5’ region of the PrP gene does not contain a canonical TATA box, is very GC rich (83% GC residues), and has numerous GC repeats. The six base-pair sequence CCGCCC is repeated four times in exon 1; such GC-rich features are commonly seen in housekeeping genes3-4.
The human PRNP gene locus contains three genes: PRNP, PRND and a novel gene, PRNT (Figure 2). PRND is a single-copy gene located 27 Kb downstream of PRNP and is also composed of a two-exon structure. A further 3 Kb downstream of PRND, is the PRNT gene5. Whereas PRND is paralogous to PRNP, PRNT exhibits no detectable sequence homology with any of the three members comprising the prion gene family, and is thought to be unlikely to be a protein-coding gene, but rather, may represent a region of mRNA-like long non-coding RNA6 (Figure 2).
In addition to PRNP, the other members of this gene family include the also neuropathologically relevant paralogs PRND (doppel protein, chromosome 20), expressed in testis and SPRN (shadoo, or shadow of prion protein, chromosome 10), expressed mainly in brain5,7-8. These three loci likely derived by retroposition of an ancestral ZIP metal ion transporter gene9. PrP is found in most adult tissue, with the highest levels of expressed protein in the central nervous system, particularly in association with synaptic membranes8.
- OMIM Entry 176640—Prion Protein; PRNP.
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