PrP systemic amyloidosis

Summary

PrP systemic amyloidosis (MONDO:0018339) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		16	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	PrP systemic amyloidosis
Mondo ID	MONDO:0018339
Orphanet	397606
SNOMED CT	733422008
UMLS	C4518776
MedGen	1377371
GARD	0021632
Is cancer (heuristic)	no

Also known as: chronic diarrhea with hereditary sensory and autonomic neuropathy · chronic diarrhea with HSAN · chronic diarrhoea with hereditary sensory and autonomic neuropathy · chronic diarrhoea with HSAN · prion protein systemic amyloidosis

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › prion disease › PrP systemic amyloidosis

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

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
PRNP	Supportive	Autosomal dominant	PrP systemic amyloidosis	14

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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PRNP	HGNC:9449	ENSG00000171867	F7VJQ1	Alternative prion protein	gencc

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRNP	Other/Unknown	no		Prion, Prion_copper_b_octapeptide, Prion/Doppel_prot_b-ribbon_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
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
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
PRNP	2,594

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRNP	F7VJQ1	70

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	1	475.8×	0.004	PRNP
NCAM1 interactions	1	248.3×	0.004	PRNP

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of glutamate receptor signaling pathway	1	3370.4×	0.003	PRNP
negative regulation of amyloid precursor protein catabolic process	1	3370.4×	0.003	PRNP
negative regulation of dendritic spine maintenance	1	2808.7×	0.003	PRNP
regulation of calcium ion import across plasma membrane	1	2808.7×	0.003	PRNP
positive regulation of glutamate receptor signaling pathway	1	1532.0×	0.003	PRNP
dendritic spine maintenance	1	1296.3×	0.003	PRNP
negative regulation of long-term synaptic potentiation	1	1296.3×	0.003	PRNP
negative regulation of protein processing	1	1123.5×	0.003	PRNP
neuron projection maintenance	1	1123.5×	0.003	PRNP
negative regulation of interleukin-17 production	1	1053.2×	0.003	PRNP
negative regulation of activated T cell proliferation	1	1053.2×	0.003	PRNP
response to amyloid-beta	1	991.3×	0.003	PRNP
intracellular copper ion homeostasis	1	936.2×	0.003	PRNP
negative regulation of calcineurin-NFAT signaling cascade	1	936.2×	0.003	PRNP
negative regulation of amyloid-beta formation	1	887.0×	0.003	PRNP
response to cadmium ion	1	732.7×	0.003	PRNP
cellular response to copper ion	1	624.1×	0.003	PRNP
regulation of potassium ion transmembrane transport	1	624.1×	0.003	PRNP
negative regulation of interleukin-2 production	1	581.1×	0.003	PRNP
positive regulation of protein targeting to membrane	1	561.7×	0.003	PRNP
long-term memory	1	421.3×	0.004	PRNP
positive regulation of calcium-mediated signaling	1	421.3×	0.004	PRNP
cellular response to amyloid-beta	1	391.9×	0.004	PRNP
negative regulation of type II interferon production	1	383.0×	0.004	PRNP
negative regulation of T cell receptor signaling pathway	1	366.4×	0.004	PRNP
protein destabilization	1	290.6×	0.005	PRNP
positive regulation of neuron apoptotic process	1	271.8×	0.005	PRNP
positive regulation of protein localization to plasma membrane	1	271.8×	0.005	PRNP
learning or memory	1	240.7×	0.005	PRNP
cellular response to xenobiotic stimulus	1	240.7×	0.005	PRNP

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRNP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	0
E	Difficult family or no structure, no drug	1	PRNP

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PRNP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.