Creutzfeldt Jacob disease

Summary

Creutzfeldt Jacob disease (MONDO:0005357) is a disease with 4 cohort genes (8 GWAS associations across 2 studies) and 2 clinical trials.

At a glance

• Cohort genes: 4
• GWAS associations: 8
• Clinical trials: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Creutzfeldt Jacob disease
Mondo ID	MONDO:0005357
EFO	EFO:0004226
MeSH	D007562
DOID	DOID:11949
NCIT	C26802
SNOMED CT	792004
UMLS	C0022336
MedGen	7179
GARD	0024173
NORD	1014
Is cancer (heuristic)	no

Also known as: CJD · CJD (Creutzfeldt Jakob disease) · classic Creutzfeldt-Jakob disease · Creutzfeldt Jakob Disease · Creutzfeldt-Jacob disease · Jakob-Creutzfeldt disease

Data availability: 8 GWAS associations (2 studies).

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › prion disease › Creutzfeldt Jacob disease

Related subtypes (9): kuru, scrapie, Gerstmann-Straussler-Scheinker syndrome, fatal familial insomnia, Huntington disease-like 1, spongiform encephalopathy with neuropsychiatric features, familial Alzheimer-like prion disease, PrP systemic amyloidosis, sporadic fatal insomnia

Subtypes (3): inherited Creutzfeldt-Jakob disease, sporadic Creutzfeldt-Jakob disease, acquired Creutzfeldt-Jakob disease

Genetics & variants

GWAS landscape

8 GWAS associations across 2 studies. Top hits map to 4 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs1799990	2e-21	PRNP	A
rs6107516	3e-18	PRNP	?
rs4921542	2e-08	MTMR7	?	3.25
rs7565981	4e-08	LINC01868 - NPAS2	?	2.98
rs1460163	6e-08	MITA1 - RPL3P9	A
rs6116492	5e-07	PRNP - PRND	?
rs1495377	2e-06	TSPAN8	?
rs12273350	2e-06	PKNOX2	?

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST000294	Mead S	2008	117	3,083	Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study.
GCST001334	Sanchez-Juan P	2011	93	1,504	Genome-wide study links MTMR7 gene to variant Creutzfeldt-Jakob risk.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	1
Tier 4: intronic/intergenic	6

MAF distribution

Bucket	Variants
common (>=0.05)	8
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	4
intergenic_variant	2
missense_variant	1
regulatory_region_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs1799990	20	4699605	A>G	0.05	missense_variant	PRNP	2e-21	Tier 1: coding
rs6107516	20	4696446	G>A	0.05	intron_variant	PRNP	3e-18	Tier 4: intronic/intergenic
rs4921542	8	17348068	T>A,C,G	0.05	intron_variant	MTMR7	2e-08	Tier 4: intronic/intergenic
rs7565981	2	100807869	G>A,C	0.05	intergenic_variant	LINC01868 - NPAS2	4e-08	Tier 4: intronic/intergenic
rs1460163	8	79315213	G>A,C,T	0.05	intron_variant	MITA1 - RPL3P9	6e-08	Tier 4: intronic/intergenic
rs6116492	20	4717980	G>T	0.05	intergenic_variant	PRNP - PRND	5e-07	Tier 4: intronic/intergenic
rs1495377	12	71183321	G>A,C,T	0.05	regulatory_region_variant	TSPAN8	2e-06	Tier 3: regulatory
rs12273350	11	125371150	G>A	0.05	intron_variant	PKNOX2	2e-06	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 1

Dual-evidence genes (GWAS + Mendelian — highest-confidence targets)

Gene	HGNC	Evidence routes
PRNP	PRNP	GWAS, Orphanet

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRNP	Orphanet:157941	Huntington disease-like 1
PRNP	Orphanet:280397	Familial Alzheimer-like prion disease
PRNP	Orphanet:282166	Inherited Creutzfeldt-Jakob disease
PRNP	Orphanet:356	Gerstmann-Straussler-Scheinker syndrome
PRNP	Orphanet:397606	PrP systemic amyloidosis
PRNP	Orphanet:454745	Kuru
PRNP	Orphanet:466	Fatal familial insomnia

Cohort genes → proteins

4 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
STMN2	HGNC:10577	ENSG00000104435	Q93045	Stathmin-2	gwas
MTMR7	HGNC:7454	ENSG00000003987	Q9Y216	Phosphatidylinositol-3-phosphate phosphatase MTMR7	gwas
NPAS2	HGNC:7895	ENSG00000170485	Q99743	Neuronal PAS domain-containing protein 2	gwas
PRNP	HGNC:9449	ENSG00000171867	F7VJQ1	Alternative prion protein	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STMN2	Stathmin-2	Regulator of microtubule stability.
MTMR7	Phosphatidylinositol-3-phosphate phosphatase MTMR7	Lipid phosphatase that specifically dephosphorylates the D-3 position of phosphatidylinositol 3-phosphate (PtdIns(3)P) and inositol 1,3-bisphosphate (Ins(1,3)P2).
NPAS2	Neuronal PAS domain-containing protein 2	Transcriptional activator which forms a core component of the circadian clock.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.25

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Phosphatase	1	21.0×	0.141
Transcription factor	1	2.1×	0.605
Other/Unknown	2	0.9×	0.769

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STMN2	Other/Unknown	no		Stathmin_fam, Stathmin_CS, Stathmin_sf
MTMR7	Phosphatase	yes		Tyr_Pase_dom, Tyr_Pase_cat, Myotubularin-like_Pase_dom
NPAS2	Transcription factor	no		PAS, Nuc_translocat, PAC
PRNP	Other/Unknown	no		Prion, Prion_copper_b_octapeptide, Prion/Doppel_prot_b-ribbon_dom

Expression context

Cohort genes with no expression data: 0.

4 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cortical plate	2
cerebellar vermis	1
pons	1
C1 segment of cervical spinal cord	1
islet of Langerhans	1
body of pancreas	1
esophagus mucosa	1
lower esophagus mucosa	1
Brodmann (1909) area 23	1
CA1 field of hippocampus	1
pigmented layer of retina	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STMN2	222	broad	marker	cortical plate, pons, cerebellar vermis
MTMR7	180	broad	marker	islet of Langerhans, cortical plate, C1 segment of cervical spinal cord
NPAS2	266	ubiquitous	marker	lower esophagus mucosa, esophagus mucosa, body of pancreas
PRNP	294	ubiquitous	marker	CA1 field of hippocampus, Brodmann (1909) area 23, pigmented layer of retina

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STMN2	2,993
PRNP	2,594
MTMR7	1,118
NPAS2	1,085

Structural data

PDB: 1 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRNP	F7VJQ1	70

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
STMN2	Q93045	85.95
MTMR7	Q9Y216	84.56
NPAS2	Q99743	61.78

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 4 evidence-associated genes (4 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Synthesis of PIPs at the late endosome membrane	1	237.9×	0.027	MTMR7
Synthesis of IP2, IP, and Ins in the cytosol	1	190.3×	0.027	MTMR7
The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex	1	178.4×	0.027	NPAS2
Inositol phosphate metabolism	1	119.0×	0.027	MTMR7
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	1	119.0×	0.027	PRNP
Phosphorylated BMAL1:CLOCK (ARNTL:CLOCK) activates expression of core clock genes	1	119.0×	0.027	NPAS2
BMAL1:CLOCK,NPAS2 activates circadian expression	1	105.7×	0.027	NPAS2
PI Metabolism	1	89.2×	0.028	MTMR7
Expression of BMAL (ARNTL), CLOCK, and NPAS2	1	73.2×	0.029	NPAS2
RND1 GTPase cycle	1	66.4×	0.029	STMN2
NCAM1 interactions	1	62.1×	0.029	PRNP
Heme signaling	1	53.9×	0.030	NPAS2
Phospholipid metabolism	1	50.1×	0.030	MTMR7
PPARA activates gene expression	1	23.6×	0.060	NPAS2
RHO GTPase cycle	1	15.0×	0.087	STMN2
Signaling by Rho GTPases	1	8.6×	0.134	STMN2
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	8.4×	0.134	STMN2
Metabolism of lipids	1	7.9×	0.134	MTMR7
Metabolism	1	2.9×	0.318	MTMR7
Signal Transduction	1	2.5×	0.339	STMN2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of microtubule depolymerization	1	842.6×	0.012	STMN2
regulation of glutamate receptor signaling pathway	1	842.6×	0.012	PRNP
negative regulation of amyloid precursor protein catabolic process	1	842.6×	0.012	PRNP
negative regulation of dendritic spine maintenance	1	702.2×	0.012	PRNP
regulation of calcium ion import across plasma membrane	1	702.2×	0.012	PRNP
positive regulation of behavioral fear response	1	601.9×	0.012	NPAS2
positive regulation of glutamate receptor signaling pathway	1	383.0×	0.012	PRNP
negative regulation of microtubule polymerization	1	324.1×	0.012	STMN2
response to redox state	1	324.1×	0.012	NPAS2
dendritic spine maintenance	1	324.1×	0.012	PRNP
negative regulation of long-term synaptic potentiation	1	324.1×	0.012	PRNP
negative regulation of protein processing	1	280.9×	0.012	PRNP
neuron projection maintenance	1	280.9×	0.012	PRNP
microtubule depolymerization	1	263.3×	0.012	STMN2
regulation of microtubule polymerization or depolymerization	1	263.3×	0.012	STMN2
negative regulation of interleukin-17 production	1	263.3×	0.012	PRNP
negative regulation of activated T cell proliferation	1	263.3×	0.012	PRNP
response to amyloid-beta	1	247.8×	0.012	PRNP
intracellular copper ion homeostasis	1	234.1×	0.012	PRNP
negative regulation of calcineurin-NFAT signaling cascade	1	234.1×	0.012	PRNP
negative regulation of amyloid-beta formation	1	221.7×	0.012	PRNP
response to cadmium ion	1	183.2×	0.014	PRNP
phosphatidylinositol dephosphorylation	1	162.0×	0.015	MTMR7
cellular response to copper ion	1	156.0×	0.015	PRNP
regulation of potassium ion transmembrane transport	1	156.0×	0.015	PRNP
negative regulation of interleukin-2 production	1	145.3×	0.015	PRNP
positive regulation of protein targeting to membrane	1	140.4×	0.015	PRNP
negative regulation of microtubule depolymerization	1	123.9×	0.016	STMN2
cellular response to nerve growth factor stimulus	1	117.0×	0.017	STMN2
long-term memory	1	105.3×	0.017	PRNP

Therapeutics

Drugs indicated or in trials for this disease

No drug has an approved disease-direct ChEMBL indication for this disease.

1 drug in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.

Drug	Highest phase
Quinacrine	Phase 2

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 4

Druggability breadth: 2 of 4 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
STMN2	0	0
MTMR7	0	0
NPAS2	0	0
PRNP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
STMN2	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 4; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	MTMR7
E	Difficult family or no structure, no drug	3	STMN2, NPAS2, PRNP

Undrugged target profiles

4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
STMN2	1	—
MTMR7	0	—
NPAS2	0	—
PRNP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05124392	Not specified	RECRUITING	Biomarker Profiling in Individuals at Risk for Prion Disease
NCT04944732	Not specified	COMPLETED	Evaluation of Diagnostic Criteria for Creutzfeldt Jakob Disease