Major prion protein
| prion protein (p27-30) | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | PRNP | ||||||
| Alt. symbols | PRIP, GSS, CJD | ||||||
| NCBI gene | 5621 | ||||||
| HGNC | 9449 | ||||||
| OMIM | 176640 | ||||||
| RefSeq | NM_000311 | ||||||
| UniProt | P04156 | ||||||
| Other data | |||||||
| Locus | Chr. 20 pter-p12 | ||||||
| |||||||
PRNP (prion protein (Creutzfeld-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, fatal familial insomnia)) is a gene that provides instructions to make a protein called the prion protein (PrP), which is active in the brain and several other tissues. Although the precise function of PrP is not yet known, it is possibly involved in the transport of charged atoms (ions) of copper to cells from the surrounding environment. Researchers have also proposed roles for PrP in cell signaling or in the formation of gaps between nerve cells (synapses) where cell-to-cell communication occurs.
Different forms of PrP have been identified in the nervous system. The usual cellular form is called PrPC. Another form, PrPSc, has a different 3-dimensional structure and has been associated with inherited, sporadic (non-inherited), and infectious disorders of the brain and nervous system. In a process that is not fully understood, PrPC can transform into the abnormal PrPSc. This abnormal protein can further promote the transformation of PrPC into PrPSc, leading to transmissible spongiform encephalopathy.
The PRNP gene is located on the short (p) arm of chromosome 20 between the end (terminus) of the arm and position 12, from base pair 4,615,068 to base pair 4,630,233.
Related conditions
More than 20 mutations in the PRNP gene have been identified in people with inherited prion diseases, which include the following:
- Creutzfeldt-Jakob disease - aspartic acid-178 is replaced by asparagine while valine is present at amino acid 129
- Gerstmann-Sträussler-Scheinker syndrome - usually a change in codon 102 from proline to leucine
- fatal insomnia - aspartic acid-178 is replaced by asparagine while methionine is present at amino acid 129
Some PRNP mutations lead to a change in single amino acids (the building blocks of proteins) in the prion protein. Others insert additional amino acids into the protein or cause an abnormally short protein to be made. These mutations cause the cell to make prion proteins with an abnormal structure. The abnormal protein, PrPSc, accumulates in the brain and destroys nerve cells, which leads to the mental and behavioral features of prion diseases. Several other changes in the PRNP gene (called polymorphisms) do not cause prion diseases, but may affect a person's risk of developing these diseases or alter the course of the disorders.
References
- Castilla J, Hetz C, Soto C (2004). "Molecular mechanisms of neurotoxicity of pathological prion protein". Curr Mol Med. 4 (4): 397–403. PMID 15354870.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Collins S, McLean CA, Masters CL (2001). "Gerstmann-Straussler-Scheinker syndrome,fatal familial insomnia, and kuru: a review of these less common human transmissible spongiform encephalopathies". J Clin Neurosci. 8 (5): 387–97. PMID 11535002.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Kovacs GG, Trabattoni G, Hainfellner JA, Ironside JW, Knight RS, Budka H (2002). "Mutations of the prion protein gene phenotypic spectrum". J Neurol. 249 (11): 1567–82. PMID 12420099.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Montagna P, Gambetti P, Cortelli P, Lugaresi E (2003). "Familial and sporadic fatal insomnia". Lancet Neurol. 2 (3): 167–76. PMID 12849238.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Prusiner SB (2001). "Shattuck lecture--neurodegenerative diseases and prions". N Engl J Med. 344 (20): 1516–26. PMID 11357156.
- Weissmann C (2004). "The state of the prion". Nat Rev Microbiol. 2 (11): 861–71. PMID 15494743.