FB2026_03 , released September 17, 2026
Human Disease Model Report: Creutzfeldt-Jakob disease, familial
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General Information
Name
Creutzfeldt-Jakob disease, familial
FlyBase ID
FBhh0000791
Disease Ontology Term
Parent Disease
OMIM
CREUTZFELDT-JAKOB DISEASE; CJD
Overview

This report describes familial Creutzfeldt-Jakob disease (CJD), one of several inherited prion diseases in humans (see MIM:176640); the disease is inherited as an autosomal dominant. The human gene implicated is the prion protein gene, PRNP. No fly gene orthologous to PRNP has been identified.

Fatal familial insomnia (FFI; FBhh0000914) and CJD are considered by some researchers to be extremes of a phenotypic spectrum and some variants of PRNP are implicated in both. Experiments in Drosophila related to Creutzfeldt-Jakob disease and/or fatal familial insomnia are described in this human disease model report. See, also, the human disease model report for 'prion diseases' (FBhh0000185).

Multiple different UAS constructs of the hamster Maur\Prp gene have been introduced into flies, including wild-type and constructs with specific mutational lesions implicated in Creutzfeldt-Jakob disease and/or fatal familial insomnia. Variant(s) implicated in human disease tested (as transgenic hamster gene, Maur\Prp): a variant corresponding to D178N in the human PRNP gene (indicated in FlyBase as Maur\PrpFFI.UAS) and a variant corresponding to E200K in the human PRNP gene (indicated in FlyBase as Maur\PrpCJD.UAS).

Multiple different UAS constructs of the mouse Mmus\Prnp gene have also been introduced into flies, including a modified wild-type (3F4 epitope) and derived constructs with specific mutational lesions implicated in Creutzfeldt-Jakob disease and/or fatal familial insomnia. Variant(s) implicated in human disease tested (as transgenic mouse gene, Mmus\Prnp): a variant corresponding to D178N in the human PRNP gene (indicated in FlyBase as Mmus\PrnpFFI.3F4.UAS); a variant corresponding to E200K in the human PRNP gene (indicated in FlyBase as Mmus\PrnpCJD.3F4.UAS); and a variant carrying the octapeptide repeat expansion implicated in CJD in human (indicated in FlyBase as Mmus\PrnpPG14.UAS.

[updated Feb. 2020 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: prion diseases
Symptoms and phenotype

The human prion diseases occur in inherited, acquired, and sporadic forms. Approximately 15% are inherited and associated with coding mutations in the PRNP gene. Inherited prion diseases include familial Creutzfeldt-Jakob disease (CJD; MIM:123400), Gerstmann-Straussler disease (GSD; MIM:137440), and fatal familial insomnia (FFI; MIM:600072). Acquired prion diseases in humans include iatrogenic CJD, kuru (MIM:245300), and variant CJD (vCJD). Variant CJD is believed to be acquired from cattle infected with BSE. The majority of human cases of prion disease occur as sporadic CJD (sCJD) (Collinge et al., 1996, pubmed:8878476; Parchi et al., 2000, pubmed:10963679; Hill et al., 2003, pubmed:12764055). [from MIM:176640; 2016.03.01]

(OMIM, 2013-)
Specific Disease Summary: Creutzfeldt-Jakob disease, familial
OMIM report

[CREUTZFELDT-JAKOB DISEASE; CJD](https://omim.org/entry/123400)

Human gene(s) implicated

[MAJOR HISTOCOMPATIBILITY COMPLEX, CLASS II, DQ BETA-1; HLA-DQB1](https://omim.org/entry/604305)

[PRION PROTEIN; PRNP](https://omim.org/entry/176640)

Symptoms and phenotype

The human prion diseases occur in inherited, acquired, and sporadic forms. The majority of human cases of prion disease occur as sporadic CJD (sCJD). Approximately 15% are inherited and associated with coding mutations in the PRNP gene. Variant CJD is believed to be acquired from cattle infected with bovine spongiform encephalopathy (BSE). (Collinge et al., 1996, pubmed:8878476; Parchi et al., 2000, pubmed:10963679; Hill et al., 2003, pubmed:12764055). [from MIM:123400; 2018.04.19]

(OMIM, 2013-)
Genetics

Some missense variants in the PRNP gene are associated with both familial CJD and fatal familial insomnia (FFI), thus, these two diseases may be part of a phenotypic spectrum. [from MIM:600072; 2018.04.19]

(OMIM, 2013-)

Familial Creutzfeldt-Jakob disease can be caused by mutation in the prion protein gene (PRNP); it is inherited as an autosomal dominant. [from MIM:123400; 2018.04.19]

(OMIM, 2013-)
Cellular phenotype and pathology
Molecular information

The protein encoded by PRNP is a membrane glycoprotein that tends to aggregate into rod-like structures. Its primary physiological function is unclear; it may be required for neuronal myelin sheath maintenance. [Gene Cards, PRNP; 2018.04.19]

(FlyBase Curators, 2013-)
External links
Disease synonyms
CJD
familial CJD
fCJD
FFI
insomnia, fatal familial
Ortholog Information
Human gene(s) in FlyBase
    Human gene (HGNC)
    Symbol / Name
    PRNP; prion protein (Kanno blood group)
    D. melanogaster ortholog (based on DIOPT)
    Comments on ortholog(s)

    There is no ortholog of the prion protein gene (PRNP) in flies.

    Other mammalian ortholog(s) used
    D. melanogaster Gene Information (0)
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (0 groups)
      Alleles Reported to Model Human Disease (Disease Ontology) (13 alleles)
      Maur\Prp
      Models Based on Experimental Evidence ( 4 )
      Modifiers Based on Experimental Evidence ( 1 )
      Allele
      Disease
      Interaction
      References
      Maur\PrpUAS.cFa
      model of  prion disease
      is ameliorated by Hsap\HSPA1LUAS.cWa
      (Fernandez-Funez et al., 2009)
      Mmus\Prnp
      Models Based on Experimental Evidence ( 9 )
      Modifiers Based on Experimental Evidence ( 0 )
      Allele
      Disease
      Interaction
      References
      Alleles Representing Disease-Implicated Variants
      Genetic Tools, Stocks and Reagents
      References (11)