Prion disease pathway (WP3995)

Prion diseases are rare, genetic, transmissible and sporadic diseases, which are caused by mutations in the PRNP gene. This gene is located on chromosome 20p13 and is composed of two exons. Mutations in the PRNP gene cause conformational changes in the prion protein (PRNP). The normal PRNP (protein) changes into the pathologic PRNP. A molecular pathway can give a better understanding in prion diseases. This pathway is a prion disease pathway, that describes what happens when there is a mutation in the PRNP gene. The left part of the pathway represents the pathway retrieved from literature and the right part of the pathway represents data found using databases. The left part shos the interaction of pathological prion protein with an unknown receptor protein, this interaction activates a signalling pathway. The endoplasmic reticulum releases calcium and ER stress is induced. Activation of Caspase 12 by ER-stress is followed by cleavage and activation of the executioner Caspase-3, causing neuronal apoptosis. According to the databases, NCAM-1 can initiate two mechanisms: the activation of FGFR and formation of intracellular signalling complexes. NCAM-1 interacts with Fyn and FAK, resulting in phosphorylation of these two tyrosine kinases. Phosphorylation of Fyn and FAK results in activation of MAPK, ERK1 and 2, cAMP response element binding protein (CREB) and transcription factors ELK and NFkB. CREB activates transcription of genes which are important for axonal growth, survival, and synaptic plasticity in neurons. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]
last edited


LvdWouw, Fehrhart, MaintBot, Mkutmon, Egonw, Khanspers, and Finterly

Cited In


Homo sapiens


Diseases Rare Diseases


Disease Ontology: prion disease

Cell Type Ontology: neuron neuron

Pathway Ontology: prion disease pathway disease pathway


Label Type Compact Identifier
RFX5 GeneProduct ensembl:ENSG00000143390
ELK1 GeneProduct ensembl:ENSG00000126767
CREB1 Protein ensembl:ENSG00000118260
FGFR1 GeneProduct ensembl:ENSG00000077782
TBP GeneProduct ensembl:ENSG00000112592
Z-DEVD-FMK Metabolite chebi:138013
BCL11A GeneProduct ensembl:ENSG00000119866
STAT3 GeneProduct ensembl:ENSG00000168610
CASP12 GeneProduct ensembl:ENSG00000204403
MAPK3 GeneProduct ensembl:ENSG00000102882
HSP90B1 GeneProduct ensembl:ENSG00000166598
RAD21 GeneProduct ensembl:ENSG00000164754
NCAM1 GeneProduct ensembl:ENSG00000149294
PDIA3 GeneProduct ensembl:ENSG00000167004
PrP Receptor ? Protein None
CTCF GeneProduct ensembl:ENSG00000102974
PAX5 GeneProduct ensembl:ENSG00000196092
FYN GeneProduct ensembl:ENSG00000010810
PRNP GeneProduct ensembl:ENSG00000171867
PRNP (+ mutations) GeneProduct ensembl:ENSG00000171867
PRNP Protein ensembl:ENSG00000171867
POU2F2 GeneProduct ensembl:ENSG00000028277
MEF2C GeneProduct ensembl:ENSG00000081189
NFKB1 GeneProduct ensembl:ENSG00000109320
CASP3 GeneProduct ensembl:ENSG00000164305
BATF GeneProduct ensembl:ENSG00000156127
SPI1 GeneProduct ensembl:ENSG00000066336
EP300 GeneProduct ensembl:ENSG00000100393
PRNP Protein ensembl:ENSG00000171867
EBF1 GeneProduct ensembl:ENSG00000164330
BCL2Anti-apoptotic GeneProduct ensembl:ENSG00000171791
IRF4 GeneProduct ensembl:ENSG00000137265
SMC3 GeneProduct ensembl:ENSG00000108055
RXRA GeneProduct ensembl:ENSG00000186350
Ca2+ Metabolite chebi:29108
MAPK1 GeneProduct ensembl:ENSG00000100030
PTK2 GeneProduct ensembl:ENSG00000169398
PRO CASP12 GeneProduct ensembl:ENSG00000204403
CHD2 GeneProduct ensembl:ENSG00000173575
PRNP (+ mutations) GeneProduct ensembl:ENSG00000171867
HSPA5 GeneProduct ensembl:ENSG00000044574
NFKB1 GeneProduct ensembl:ENSG00000109320
FYN GeneProduct ensembl:ENSG00000010810
PTK2 GeneProduct ensembl:ENSG00000169398


  1. Hetz C, Russelakis-Carneiro M, Maundrell K, Castilla J, Soto C. Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein. EMBO J. 2003 Oct 15;22(20):5435–45. PubMed Europe PMC Scholia