Major prion protein

NameMajor prion protein
Synonyms
  • ALTPRP
  • ASCR
  • PRIP
  • PRP
  • PrP27-30
  • PrP33-35C
Gene NamePRNP
OrganismHuman
Amino acid sequence
>lcl|BSEQ0002199|Major prion protein
MANLGCWMLVLFVATWSDLGLCKKRPKPGGWNTGGSRYPGQGSPGGNRYPPQGGGGWGQP
HGGGWGQPHGGGWGQPHGGGWGQPHGGGWGQGGGTHSQWNKPSKPKTNMKHMAGAAAAGA
VVGGLGGYMLGSAMSRPIIHFGSDYEDRYYRENMHRYPNQVYYRPMDEYSNQNNFVHDCV
NITIKQHTVTTTTKGENFTETDVKMMERVVEQMCITQYERESQAYYQRGSSMVLFSSPPV
ILLISFLIFLIVG
Number of residues253
Molecular Weight27661.21
Theoretical pI9.23
GO Classification
Functions
  • microtubule binding
  • identical protein binding
  • tubulin binding
  • copper ion binding
Processes
  • negative regulation of calcineurin-NFAT signaling cascade
  • learning or memory
  • response to oxidative stress
  • regulation of potassium ion transmembrane transport
  • cell cycle arrest
  • regulation of protein localization
  • negative regulation of interleukin-17 production
  • negative regulation of protein phosphorylation
  • axon guidance
  • metabolic process
  • negative regulation of interleukin-2 production
  • negative regulation of apoptotic process
  • cellular copper ion homeostasis
  • cellular response to copper ion
  • cellular response to drug
  • response to cadmium ion
  • negative regulation of T cell receptor signaling pathway
  • negative regulation of interferon-gamma production
  • protein homooligomerization
  • negative regulation of activated T cell proliferation
  • negative regulation of sequence-specific DNA binding transcription factor activity
Components
  • anchored component of membrane
  • nucleus
  • endoplasmic reticulum
  • plasma membrane
  • extrinsic component of membrane
  • cell surface
  • Golgi apparatus
  • extracellular exosome
  • membrane raft
  • cytoplasm
General FunctionTubulin binding
Specific FunctionIts primary physiological function is unclear. Has cytoprotective activity against internal or environmental stresses. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro) (PubMed:12732622, PubMed:19936054, PubMed:20564047). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or ZN(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID190468
UniProtKB IDP04156
UniProtKB Entry NamePRIO_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0019060|Major prion protein (PRNP)
ATGGCGAACCTTGGCTGCTGGATGCTGGTTCTCTTTGTGGCCACATGGAGTGACCTGGGC
CTCTGCAAGAAGCGCCCGAAGCCTGGAGGATGGAACACTGGGGGCAGCCGATACCCGGGG
CAGGGCAGCCCTGGAGGCAACCGCTACCCACCTCAGGGCGGTGGTGGCTGGGGGCAGCCT
CATGGTGGTGGCTGGGGGCAGCCTCATGGTGGTGGCTGGGGGCAGCCCCATGGTGGTGGC
TGGGGACAGCCTCATGGTGGTGGCTGGGGTCAAGGAGGTGGCACCCACAGTCAGTGGAAC
AAGCCGAGTAAGCCAAAAACCAACATGAAGCACATGGCTGGTGCTGCAGCAGCTGGGGCA
GTGGTGGGGGGCCTTGGCGGCTACATGCTGGGAAGTGCCATGAGCAGGCCCATCATACAT
TTCGGCAGTGACTATGAGGACCGTTACTATCGTGAAAACATGCACCGTTACCCCAACCAA
GTGTACTACAGGCCCATGGATGAGTACAGCAACCAGAACAACTTTGTGCACGACTGCGTC
AATATCACAATCAAGCAGCACACGGTCACCACAACCACCAAGGGGGAGAACTTCACCGAG
ACCGACGTTAAGATGATGGAGCGCGTGGTTGAGCAGATGTGTATCACCCAGTACGAGAGG
GAATCTCAGGCCTATTACCAGAGAGGATCGAGCATGGTCCTCTTCTCCTCTCCACCTGTG
ATCCTCCTGATCTCTTTCCTCATCTTCCTGATAGTGGGATGA
GenBank Gene IDM13899
GeneCard IDNot Available
GenAtlas IDPRNP
HGNC IDHGNC:9449
Chromosome Location20
Locus20p13
References
  1. Kretzschmar HA, Stowring LE, Westaway D, Stubblebine WH, Prusiner SB, Dearmond SJ: Molecular cloning of a human prion protein cDNA. DNA. 1986 Aug;5(4):315-24. 3755672
  2. Puckett C, Concannon P, Casey C, Hood L: Genomic structure of the human prion protein gene. Am J Hum Genet. 1991 Aug;49(2):320-9. 1678248
  3. Lee IY, Westaway D, Smit AF, Wang K, Seto J, Chen L, Acharya C, Ankener M, Baskin D, Cooper C, Yao H, Prusiner SB, Hood LE: Complete genomic sequence and analysis of the prion protein gene region from three mammalian species. Genome Res. 1998 Oct;8(10):1022-37. 9799790
  4. Cervenakova L, Buetefisch C, Lee HS, Taller I, Stone G, Gibbs CJ Jr, Brown P, Hallett M, Goldfarb LG: Novel PRNP sequence variant associated with familial encephalopathy. Am J Med Genet. 1999 Dec 15;88(6):653-6. 10581485
  5. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. 11780052
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Liao YC, Lebo RV, Clawson GA, Smuckler EA: Human prion protein cDNA: molecular cloning, chromosomal mapping, and biological implications. Science. 1986 Jul 18;233(4761):364-7. 3014653
  8. Diedrich JF, Knopman DS, List JF, Olson K, Frey WH 2nd, Emory CR, Sung JH, Haase AT: Deletion in the prion protein gene in a demented patient. Hum Mol Genet. 1992 Sep;1(6):443-4. 1363802
  9. Samaia HB, Mari JJ, Vallada HP, Moura RP, Simpson AJ, Brentani RR: A prion-linked psychiatric disorder. Nature. 1997 Nov 20;390(6657):241. 9384372
  10. Perry RT, Go RC, Harrell LE, Acton RT: SSCP analysis and sequencing of the human prion protein gene (PRNP) detects two different 24 bp deletions in an atypical Alzheimer's disease family. Am J Med Genet. 1995 Feb 27;60(1):12-8. 7485229
  11. Tagliavini F, Prelli F, Ghiso J, Bugiani O, Serban D, Prusiner SB, Farlow MR, Ghetti B, Frangione B: Amyloid protein of Gerstmann-Straussler-Scheinker disease (Indiana kindred) is an 11 kd fragment of prion protein with an N-terminal glycine at codon 58. EMBO J. 1991 Mar;10(3):513-9. 1672107
  12. Goldfarb LG, Brown P, McCombie WR, Goldgaber D, Swergold GD, Wills PR, Cervenakova L, Baron H, Gibbs CJ Jr, Gajdusek DC: Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10926-30. 1683708
  13. Xiang F, Almqvist EW, Huq M, Lundin A, Hayden MR, Edstrom L, Anvret M, Zhang Z: A Huntington disease-like neurodegenerative disorder maps to chromosome 20p. Am J Hum Genet. 1998 Nov;63(5):1431-8. 9792871
  14. Mani K, Cheng F, Havsmark B, Jonsson M, Belting M, Fransson LA: Prion, amyloid beta-derived Cu(II) ions, or free Zn(II) ions support S-nitroso-dependent autocleavage of glypican-1 heparan sulfate. J Biol Chem. 2003 Oct 3;278(40):38956-65. Epub 2003 May 5. 12732622
  15. Capellari S, Zaidi SI, Long AC, Kwon EE, Petersen RB: The Thr183Ala Mutation, Not the Loss of the First Glycosylation Site, Alters the Physical Properties of the Prion Protein. J Alzheimers Dis. 2000 Mar;2(1):27-35. 12214108
  16. Chattopadhyay M, Walter ED, Newell DJ, Jackson PJ, Aronoff-Spencer E, Peisach J, Gerfen GJ, Bennett B, Antholine WE, Millhauser GL: The octarepeat domain of the prion protein binds Cu(II) with three distinct coordination modes at pH 7.4. J Am Chem Soc. 2005 Sep 14;127(36):12647-56. 16144413
  17. Walter ED, Stevens DJ, Visconte MP, Millhauser GL: The prion protein is a combined zinc and copper binding protein: Zn2+ alters the distribution of Cu2+ coordination modes. J Am Chem Soc. 2007 Dec 19;129(50):15440-1. Epub 2007 Nov 23. 18034490
  18. Juanes ME, Elvira G, Garcia-Grande A, Calero M, Gasset M: Biosynthesis of prion protein nucleocytoplasmic isoforms by alternative initiation of translation. J Biol Chem. 2009 Jan 30;284(5):2787-94. doi: 10.1074/jbc.M804051200. Epub 2008 Dec 5. 19059915
  19. Wollscheid B, Bausch-Fluck D, Henderson C, O'Brien R, Bibel M, Schiess R, Aebersold R, Watts JD: Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins. Nat Biotechnol. 2009 Apr;27(4):378-86. doi: 10.1038/nbt.1532. Epub 2009 Apr 6. 19349973
  20. Taylor DR, Whitehouse IJ, Hooper NM: Glypican-1 mediates both prion protein lipid raft association and disease isoform formation. PLoS Pathog. 2009 Nov;5(11):e1000666. doi: 10.1371/journal.ppat.1000666. Epub 2009 Nov 20. 19936054
  21. Stevens DJ, Walter ED, Rodriguez A, Draper D, Davies P, Brown DR, Millhauser GL: Early onset prion disease from octarepeat expansion correlates with copper binding properties. PLoS Pathog. 2009 Apr;5(4):e1000390. doi: 10.1371/journal.ppat.1000390. Epub 2009 Apr 17. 19381258
  22. Adrover M, Pauwels K, Prigent S, de Chiara C, Xu Z, Chapuis C, Pastore A, Rezaei H: Prion fibrillization is mediated by a native structural element that comprises helices H2 and H3. J Biol Chem. 2010 Jul 2;285(27):21004-12. doi: 10.1074/jbc.M110.111815. Epub 2010 Apr 7. 20375014
  23. Wu D, Zhang W, Luo Q, Luo K, Huang L, Wang W, Huang T, Chen R, Lin Y, Pang D, Xiao G: Copper (II) promotes the formation of soluble neurotoxic PrP oligomers in acidic environment. J Cell Biochem. 2010 Oct 15;111(3):627-33. doi: 10.1002/jcb.22743. 20564047
  24. Vanderperre B, Staskevicius AB, Tremblay G, McCoy M, O'Neill MA, Cashman NR, Roucou X: An overlapping reading frame in the PRNP gene encodes a novel polypeptide distinct from the prion protein. FASEB J. 2011 Jul;25(7):2373-86. doi: 10.1096/fj.10-173815. Epub 2011 Apr 8. 21478263
  25. Mishra M, Inoue N, Heese K: Characterizing the novel protein p33MONOX. Mol Cell Biochem. 2011 Apr;350(1-2):127-34. doi: 10.1007/s11010-010-0690-4. Epub 2010 Dec 14. 21153684
  26. Zhang Y, Swietnicki W, Zagorski MG, Surewicz WK, Sonnichsen FD: Solution structure of the E200K variant of human prion protein. Implications for the mechanism of pathogenesis in familial prion diseases. J Biol Chem. 2000 Oct 27;275(43):33650-4. 10954699
  27. Zahn R, Liu A, Luhrs T, Riek R, von Schroetter C, Lopez Garcia F, Billeter M, Calzolai L, Wider G, Wuthrich K: NMR solution structure of the human prion protein. Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):145-50. 10618385
  28. Calzolai L, Lysek DA, Guntert P, von Schroetter C, Riek R, Zahn R, Wuthrich K: NMR structures of three single-residue variants of the human prion protein. Proc Natl Acad Sci U S A. 2000 Jul 18;97(15):8340-5. 10900000
  29. Knaus KJ, Morillas M, Swietnicki W, Malone M, Surewicz WK, Yee VC: Crystal structure of the human prion protein reveals a mechanism for oligomerization. Nat Struct Biol. 2001 Sep;8(9):770-4. 11524679
  30. Burns CS, Aronoff-Spencer E, Dunham CM, Lario P, Avdievich NI, Antholine WE, Olmstead MM, Vrielink A, Gerfen GJ, Peisach J, Scott WG, Millhauser GL: Molecular features of the copper binding sites in the octarepeat domain of the prion protein. Biochemistry. 2002 Mar 26;41(12):3991-4001. 11900542
  31. Zahn R: The octapeptide repeats in mammalian prion protein constitute a pH-dependent folding and aggregation site. J Mol Biol. 2003 Nov 28;334(3):477-88. 14623188
  32. Palmer MS, Collinge J: Mutations and polymorphisms in the prion protein gene. Hum Mutat. 1993;2(3):168-73. 8364585
  33. Prusiner SB: Genetic and infectious prion diseases. Arch Neurol. 1993 Nov;50(11):1129-53. 8105771
  34. Sawaya MR, Sambashivan S, Nelson R, Ivanova MI, Sievers SA, Apostol MI, Thompson MJ, Balbirnie M, Wiltzius JJ, McFarlane HT, Madsen AO, Riekel C, Eisenberg D: Atomic structures of amyloid cross-beta spines reveal varied steric zippers. Nature. 2007 May 24;447(7143):453-7. Epub 2007 Apr 29. 17468747
  35. Antonyuk SV, Trevitt CR, Strange RW, Jackson GS, Sangar D, Batchelor M, Cooper S, Fraser C, Jones S, Georgiou T, Khalili-Shirazi A, Clarke AR, Hasnain SS, Collinge J: Crystal structure of human prion protein bound to a therapeutic antibody. Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2554-8. doi: 10.1073/pnas.0809170106. Epub 2009 Feb 9. 19204296
  36. Lee S, Antony L, Hartmann R, Knaus KJ, Surewicz K, Surewicz WK, Yee VC: Conformational diversity in prion protein variants influences intermolecular beta-sheet formation. EMBO J. 2010 Jan 6;29(1):251-62. doi: 10.1038/emboj.2009.333. Epub 2009 Nov 19. 19927125
  37. Hsiao K, Baker HF, Crow TJ, Poulter M, Owen F, Terwilliger JD, Westaway D, Ott J, Prusiner SB: Linkage of a prion protein missense variant to Gerstmann-Straussler syndrome. Nature. 1989 Mar 23;338(6213):342-5. 2564168
  38. Doh-ura K, Tateishi J, Sasaki H, Kitamoto T, Sakaki Y: Pro----leu change at position 102 of prion protein is the most common but not the sole mutation related to Gerstmann-Straussler syndrome. Biochem Biophys Res Commun. 1989 Sep 15;163(2):974-9. 2783132
  39. Medori R, Montagna P, Tritschler HJ, LeBlanc A, Cortelli P, Tinuper P, Lugaresi E, Gambetti P: Fatal familial insomnia: a second kindred with mutation of prion protein gene at codon 178. Neurology. 1992 Mar;42(3 Pt 1):669-70. 1347910
  40. Goldfarb LG, Haltia M, Brown P, Nieto A, Kovanen J, McCombie WR, Trapp S, Gajdusek DC: New mutation in scrapie amyloid precursor gene (at codon 178) in Finnish Creutzfeldt-Jakob kindred. Lancet. 1991 Feb 16;337(8738):425. 1671440
  41. Goldfarb LG, Mitrova E, Brown P, Toh BK, Gajdusek DC: Mutation in codon 200 of scrapie amyloid protein gene in two clusters of Creutzfeldt-Jakob disease in Slovakia. Lancet. 1990 Aug 25;336(8713):514-5. 1975028
  42. Hsiao K, Dlouhy SR, Farlow MR, Cass C, Da Costa M, Conneally PM, Hodes ME, Ghetti B, Prusiner SB: Mutant prion proteins in Gerstmann-Straussler-Scheinker disease with neurofibrillary tangles. Nat Genet. 1992 Apr;1(1):68-71. 1363810
  43. Goldfarb LG, Petersen RB, Tabaton M, Brown P, LeBlanc AC, Montagna P, Cortelli P, Julien J, Vital C, Pendelbury WW, et al.: Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism. Science. 1992 Oct 30;258(5083):806-8. 1439789
  44. Kitamoto T, Ohta M, Doh-ura K, Hitoshi S, Terao Y, Tateishi J: Novel missense variants of prion protein in Creutzfeldt-Jakob disease or Gerstmann-Straussler syndrome. Biochem Biophys Res Commun. 1993 Mar 15;191(2):709-14. 8461023
  45. Pocchiari M, Salvatore M, Cutruzzola F, Genuardi M, Allocatelli CT, Masullo C, Macchi G, Alema G, Galgani S, Xi YG, et al.: A new point mutation of the prion protein gene in Creutzfeldt-Jakob disease. Ann Neurol. 1993 Dec;34(6):802-7. 7902693
  46. Yamada M, Itoh Y, Fujigasaki H, Naruse S, Kaneko K, Kitamoto T, Tateishi J, Otomo E, Hayakawa M, Tanaka J, et al.: A missense mutation at codon 105 with codon 129 polymorphism of the prion protein gene in a new variant of Gerstmann-Straussler-Scheinker disease. Neurology. 1993 Dec;43(12):2723-4. 7902972
  47. Itoh Y, Yamada M, Hayakawa M, Shozawa T, Tanaka J, Matsushita M, Kitamoto T, Tateishi J, Otomo E: A variant of Gerstmann-Straussler-Scheinker disease carrying codon 105 mutation with codon 129 polymorphism of the prion protein gene: a clinicopathological study. J Neurol Sci. 1994 Dec 1;127(1):77-86. 7699395
  48. Inoue I, Kitamoto T, Doh-ura K, Shii H, Goto I, Tateishi J: Japanese family with Creutzfeldt-Jakob disease with codon 200 point mutation of the prion protein gene. Neurology. 1994 Feb;44(2):299-301. 7906019
  49. Gabizon R, Rosenman H, Meiner Z, Kahana I, Kahana E, Shugart Y, Ott J, Prusiner SB: Mutation in codon 200 and polymorphism in codon 129 of the prion protein gene in Libyan Jews with Creutzfeldt-Jakob disease. Philos Trans R Soc Lond B Biol Sci. 1994 Mar 29;343(1306):385-90. 7913755
  50. Young K, Jones CK, Piccardo P, Lazzarini A, Golbe LI, Zimmerman TR Jr, Dickson DW, McLachlan DC, St George-Hyslop P, Lennox A, et al.: Gerstmann-Straussler-Scheinker disease with mutation at codon 102 and methionine at codon 129 of PRNP in previously unreported patients. Neurology. 1995 Jun;45(6):1127-34. 7783876
  51. Barbanti P, Fabbrini G, Salvatore M, Petraroli R, Cardone F, Maras B, Equestre M, Macchi G, Lenzi GL, Pocchiari M: Polymorphism at codon 129 or codon 219 of PRNP and clinical heterogeneity in a previously unreported family with Gerstmann-Straussler-Scheinker disease (PrP-P102L mutation). Neurology. 1996 Sep;47(3):734-41. 8797472
  52. Mastrianni JA, Iannicola C, Myers RM, DeArmond S, Prusiner SB: Mutation of the prion protein gene at codon 208 in familial Creutzfeldt-Jakob disease. Neurology. 1996 Nov;47(5):1305-12. 8909447
  53. Nitrini R, Rosemberg S, Passos-Bueno MR, da Silva LS, Iughetti P, Papadopoulos M, Carrilho PM, Caramelli P, Albrecht S, Zatz M, LeBlanc A: Familial spongiform encephalopathy associated with a novel prion protein gene mutation. Ann Neurol. 1997 Aug;42(2):138-46. 9266722
  54. Piccardo P, Dlouhy SR, Lievens PM, Young K, Bird TD, Nochlin D, Dickson DW, Vinters HV, Zimmerman TR, Mackenzie IR, Kish SJ, Ang LC, De Carli C, Pocchiari M, Brown P, Gibbs CJ Jr, Gajdusek DC, Bugiani O, Ironside J, Tagliavini F, Ghetti B: Phenotypic variability of Gerstmann-Straussler-Scheinker disease is associated with prion protein heterogeneity. J Neuropathol Exp Neurol. 1998 Oct;57(10):979-88. 9786248
  55. Shibuya S, Higuchi J, Shin RW, Tateishi J, Kitamoto T: Protective prion protein polymorphisms against sporadic Creutzfeldt-Jakob disease. Lancet. 1998 Feb 7;351(9100):419. 9482303
  56. Windl O, Giese A, Schulz-Schaeffer W, Zerr I, Skworc K, Arendt S, Oberdieck C, Bodemer M, Poser S, Kretzschmar HA: Molecular genetics of human prion diseases in Germany. Hum Genet. 1999 Sep;105(3):244-52. 10987652
  57. Finckh U, Muller-Thomsen T, Mann U, Eggers C, Marksteiner J, Meins W, Binetti G, Alberici A, Hock C, Nitsch RM, Gal A: High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. Am J Hum Genet. 2000 Jan;66(1):110-7. 10631141
  58. Peoc'h K, Manivet P, Beaudry P, Attane F, Besson G, Hannequin D, Delasnerie-Laupretre N, Laplanche JL: Identification of three novel mutations (E196K, V203I, E211Q) in the prion protein gene (PRNP) in inherited prion diseases with Creutzfeldt-Jakob disease phenotype. Hum Mutat. 2000 May;15(5):482. 10790216
  59. Panegyres PK, Toufexis K, Kakulas BA, Cernevakova L, Brown P, Ghetti B, Piccardo P, Dlouhy SR: A new PRNP mutation (G131V) associated with Gerstmann-Straussler-Scheinker disease. Arch Neurol. 2001 Nov;58(11):1899-902. 11709001
  60. Mead S, Stumpf MP, Whitfield J, Beck JA, Poulter M, Campbell T, Uphill JB, Goldstein D, Alpers M, Fisher EM, Collinge J: Balancing selection at the prion protein gene consistent with prehistoric kurulike epidemics. Science. 2003 Apr 25;300(5619):640-3. Epub 2003 Apr 10. 12690204
  61. Mead S, Whitfield J, Poulter M, Shah P, Uphill J, Campbell T, Al-Dujaily H, Hummerich H, Beck J, Mein CA, Verzilli C, Whittaker J, Alpers MP, Collinge J: A novel protective prion protein variant that colocalizes with kuru exposure. N Engl J Med. 2009 Nov 19;361(21):2056-65. doi: 10.1056/NEJMoa0809716. 19923577
  62. Asante EA, Smidak M, Grimshaw A, Houghton R, Tomlinson A, Jeelani A, Jakubcova T, Hamdan S, Richard-Londt A, Linehan JM, Brandner S, Alpers M, Whitfield J, Mead S, Wadsworth JD, Collinge J: A naturally occurring variant of the human prion protein completely prevents prion disease. Nature. 2015 Jun 25;522(7557):478-81. doi: 10.1038/nature14510. Epub 2015 Jun 10. 26061765