Prion disease pathway (Homo sapiens)

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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

Quality Tags

Ontology Terms



  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 PubMed Europe PMC
  2. Reactome team, Miller R, Bohler A; ''NCAM signaling for neurite out-growth (Homo sapiens)''; Wikipathways,


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108089view11:55, 28 November 2019FehrhartOntology Term : 'disease pathway' added !
106531view23:51, 5 September 2019KhanspersModified description
105792view19:49, 15 August 2019KhanspersModified description
104288view12:48, 15 May 2019FehrhartOntology Term : 'CL:0000540' removed !
96400view10:15, 12 March 2018EgonwReplaced a secondary ChEBI identifier with a primary identifier.
94740view15:08, 5 October 2017Mkutmonfix unconnected line
93157view14:41, 1 August 2017FehrhartRe-added Z-DEVD-FMK after being added to ChEBI
93045view09:03, 27 July 2017FehrhartConnected interactions
92788view12:26, 6 July 2017LvdWouwModified description
92787view12:09, 6 July 2017LvdWouw
92775view08:31, 4 July 2017LvdWouw
92774view08:03, 4 July 2017LvdWouw
92752view12:01, 3 July 2017LvdWouwAdded PRNP regulators from ENCODE
92750view06:14, 3 July 2017FehrhartOntology Term : 'neuron' added !
92749view06:12, 3 July 2017FehrhartOntology Term : 'prion disease' added !
92720view08:15, 30 June 2017LvdWouw
92718view07:06, 30 June 2017LvdWouw
92705view09:03, 29 June 2017LvdWouw
92683view17:41, 28 June 2017MaintBotfixed unconnected
92664view16:21, 27 June 2017LvdWouwOntology Term : 'prion diseases pathway' added !
92663view16:21, 27 June 2017LvdWouwOntology Term : 'PW:0000267' removed !
92662view16:20, 27 June 2017LvdWouwOntology Term : 'neuron' added !
92661view16:19, 27 June 2017LvdWouwModified title
92660view16:19, 27 June 2017LvdWouwModified title
92659view16:17, 27 June 2017LvdWouw
92658view16:08, 27 June 2017LvdWouwModified description
92657view16:07, 27 June 2017LvdWouwModified description
92522view10:56, 13 June 2017FehrhartOntology Term : 'fatal familial insomnia pathway' added !
92519view08:12, 13 June 2017LvdWouw
92518view07:52, 13 June 2017LvdWouwAdded state (phosphorylation)
92514view07:56, 12 June 2017LvdWouw
92513view07:56, 12 June 2017LvdWouw
92512view07:47, 12 June 2017LvdWouwModified title
92511view07:47, 12 June 2017LvdWouwModified title
92510view07:47, 12 June 2017LvdWouwNew pathway

External references


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NameTypeDatabase referenceComment
BATFGeneProductENSG00000156127 (Ensembl)
BCL11AGeneProductENSG00000119866 (Ensembl)
BCL2 Anti-apoptoticGeneProductENSG00000171791 (Ensembl)
CASP12GeneProductENSG00000204403 (Ensembl)
CASP3GeneProductENSG00000164305 (Ensembl)
CHD2GeneProductENSG00000173575 (Ensembl)
CREB1ProteinENSG00000118260 (Ensembl)
CTCFGeneProductENSG00000102974 (Ensembl)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
EBF1GeneProductENSG00000164330 (Ensembl)
ELK1GeneProductENSG00000126767 (Ensembl)
EP300GeneProductENSG00000100393 (Ensembl)
FGFR1GeneProductENSG00000077782 (Ensembl)
FYNGeneProductENSG00000010810 (Ensembl)
HSP90B1GeneProductENSG00000166598 (Ensembl)
HSPA5GeneProductENSG00000044574 (Ensembl)
IRF4GeneProductENSG00000137265 (Ensembl)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
MEF2CGeneProductENSG00000081189 (Ensembl)
NCAM1GeneProductENSG00000149294 (Ensembl)
NFKB1GeneProductENSG00000109320 (Ensembl)
PAX5GeneProductENSG00000196092 (Ensembl)
PDIA3GeneProductENSG00000167004 (Ensembl)
POU2F2GeneProductENSG00000028277 (Ensembl)
PRNP (+ mutations)GeneProductENSG00000171867 (Ensembl)
PRNPProteinENSG00000171867 (Ensembl)
PRO CASP12GeneProductENSG00000204403 (Ensembl)
PTK2GeneProductENSG00000169398 (Ensembl)
PrP Receptor ?Protein
RAD21GeneProductENSG00000164754 (Ensembl)
RFX5GeneProductENSG00000143390 (Ensembl)
RXRAGeneProductENSG00000186350 (Ensembl)
SMC3GeneProductENSG00000108055 (Ensembl)
SPI1GeneProductENSG00000066336 (Ensembl)
STAT3GeneProductENSG00000168610 (Ensembl)
TBPGeneProductENSG00000112592 (Ensembl)
Z-DEVD-FMKMetaboliteCHEBI:138013 (ChEBI)

Annotated Interactions

No annotated interactions

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