PRNP

Summary

PRNP (prion protein (Kanno blood group), HGNC:9449) is a protein-coding gene on chromosome 20p13, encoding Alternative prion protein (F7VJQ1).

The protein encoded by this gene is a membrane glycosylphosphatidylinositol-anchored glycoprotein that tends to aggregate into rod-like structures. The encoded protein contains a highly unstable region of five tandem octapeptide repeats. This gene is found on chromosome 20, approximately 20 kbp upstream of a gene which encodes a biochemically and structurally similar protein to the one encoded by this gene. Mutations in the repeat region as well as elsewhere in this gene have been associated with Creutzfeldt-Jakob disease, fatal familial insomnia, Gerstmann-Straussler disease, Huntington disease-like 1, and kuru. An overlapping open reading frame has been found for this gene that encodes a smaller, structurally unrelated protein, AltPrp. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5621 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Gerstmann-Straussler-Scheinker syndrome (Definitive, GenCC) — +5 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 203 total — 17 pathogenic, 8 likely-pathogenic
• GTEx eGene: eQTL in 34 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 155
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.04 (unconstrained)
• MANE Select transcript: NM_000311

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9449
Approved symbol	PRNP
Name	prion protein (Kanno blood group)
Location	20p13
Locus type	gene with protein product
Status	Approved
Aliases	CD230, PRP, AltPrP
Ensembl gene	ENSG00000171867
Ensembl biotype	protein_coding
OMIM	176640
Entrez	5621

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

MANE Select: ENST00000379440

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4

ENST00000379440, ENST00000424424, ENST00000430350, ENST00000457586, ENST00000882184, ENST00000882185, ENST00000882186, ENST00000882187, ENST00000882188, ENST00000967833, ENST00000967834, ENST00000967835, ENST00001131840

RefSeq mRNA: 6 — MANE Select: NM_000311 NM_000311, NM_001080121, NM_001080122, NM_001080123, NM_001271561, NM_183079

CCDS: CCDS13080

Canonical transcript exons

ENST00000379440 — 2 exons

Exon	Start	End
ENSE00001957346	4686456	4686512
ENSE00003892168	4699211	4701588

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 163.8198 / max 3287.9914, expressed in 1816 samples.

Highest expression (Bgee): CA1 field of hippocampus, Brodmann (1909) area 23, pigmented layer of retina, endothelial cell, orbitofrontal cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRNP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 34 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 34 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellum	eqtl	9.4e-32	-0.54	20:4613886:C:T
Brain Cerebellar Hemisphere	eqtl	1.1e-30	-0.48	20:4613886:C:T
Cells Cultured fibroblasts	eqtl	5.3e-25	+0.28	20:4687183:T:C
Nerve Tibial	eqtl	2.7e-18	-0.16	20:4663722:A:G
Esophagus Muscularis	eqtl	3.3e-18	+0.32	20:4689864:G:A
Artery Tibial	eqtl	2.6e-14	+0.22	20:4699605:A:G
Testis	eqtl	7.5e-13	-0.15	20:4611334:G:C
Skin Sun Exposed Lower leg	eqtl	4.0e-08	-0.17	20:4692886:G:A
Esophagus Gastroesophageal Junction	eqtl	1.2e-07	+0.21	20:4687183:T:C
Muscle Skeletal	eqtl	2.7e-07	+0.15	20:4613330:G:A
Colon Sigmoid	eqtl	1.2e-06	+0.21	20:4689864:G:A
Adipose Subcutaneous	eqtl	1.9e-06	+0.13	20:4687183:T:C
Skin Not Sun Exposed Suprapubic	eqtl	4.2e-06	-0.17	20:4686278:C:G
Lung	eqtl	4.9e-06	-0.19	20:4686278:C:G
Brain Hippocampus	eqtl	1.8e-05	+0.81	20:4598662:G:A
Pancreas	eqtl	4.3e-05	+0.19	20:4687183:T:C
Breast Mammary Tissue	eqtl	5.8e-05	+0.13	20:4694509:A:T
Brain Cortex	eqtl	1.1e-04	+0.88	20:4780556:C:T
Adipose Visceral Omentum	eqtl	3.5e-04	-0.17	20:4692886:G:A
Esophagus Mucosa	eqtl	3.9e-04	+0.14	20:4687682:T:G

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
183278	148.0013	1814
187012	33.8498	1820
183277	13.2758	1452
183292	1.1186	563
183280	0.7988	511
183279	0.6152	386
187011	0.0072	2
187010	0.0030	1

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
CA1 field of hippocampus	UBERON:0003881	99.86	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.86	gold quality
pigmented layer of retina	UBERON:0001782	99.78	gold quality
endothelial cell	CL:0000115	99.76	gold quality
orbitofrontal cortex	UBERON:0004167	99.76	gold quality
dorsal root ganglion	UBERON:0000044	99.75	gold quality
pons	UBERON:0000988	99.72	gold quality
trigeminal ganglion	UBERON:0001675	99.72	gold quality
choroid plexus epithelium	UBERON:0003911	99.72	gold quality
substantia nigra pars compacta	UBERON:0001965	99.70	gold quality
germinal epithelium of ovary	UBERON:0001304	99.68	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.68	gold quality
cerebellar vermis	UBERON:0004720	99.66	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.65	gold quality
superior frontal gyrus	UBERON:0002661	99.64	gold quality
superior vestibular nucleus	UBERON:0007227	99.64	gold quality
parietal lobe	UBERON:0001872	99.60	gold quality
subthalamic nucleus	UBERON:0001906	99.60	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.59	gold quality
lateral globus pallidus	UBERON:0002476	99.59	gold quality
adult organism	UBERON:0007023	99.59	gold quality
occipital lobe	UBERON:0002021	99.58	gold quality
postcentral gyrus	UBERON:0002581	99.58	gold quality
entorhinal cortex	UBERON:0002728	99.58	gold quality
olfactory bulb	UBERON:0002264	99.56	gold quality
primary visual cortex	UBERON:0002436	99.53	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.53	gold quality
parietal pleura	UBERON:0002400	99.52	gold quality
middle temporal gyrus	UBERON:0002771	99.48	gold quality
prefrontal cortex	UBERON:0000451	99.47	gold quality
medulla oblongata	UBERON:0001896	99.47	gold quality
inferior vagus X ganglion	UBERON:0005363	99.46	gold quality
ventral tegmental area	UBERON:0002691	99.44	gold quality
pleura	UBERON:0000977	99.41	gold quality
gingival epithelium	UBERON:0001949	99.40	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.40	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.39	gold quality
frontal cortex	UBERON:0001870	99.38	gold quality
corpus callosum	UBERON:0002336	99.36	gold quality
urethra	UBERON:0000057	99.35	gold quality
seminal vesicle	UBERON:0000998	99.33	gold quality
visceral pleura	UBERON:0002401	99.29	gold quality
cerebellum	UBERON:0002037	99.28	gold quality
penis	UBERON:0000989	99.26	gold quality
frontal pole	UBERON:0002795	99.25	gold quality
cerebellar cortex	UBERON:0002129	99.24	gold quality
Ammon’s horn	UBERON:0001954	99.23	gold quality
cerebellar hemisphere	UBERON:0002245	99.23	gold quality
temporal lobe	UBERON:0001871	99.21	gold quality
gingiva	UBERON:0001828	99.19	gold quality
cerebral cortex	UBERON:0000956	99.18	gold quality
mammary duct	UBERON:0001765	99.17	gold quality
telencephalon	UBERON:0001893	99.16	gold quality
caudate nucleus	UBERON:0001873	99.13	gold quality
neocortex	UBERON:0001950	99.13	gold quality
cervix squamous epithelium	UBERON:0006922	99.12	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.10	gold quality
nucleus accumbens	UBERON:0001882	99.09	gold quality
right frontal lobe	UBERON:0002810	99.09	gold quality
mucosa of paranasal sinus	UBERON:0005030	99.09	gold quality
mammalian vulva	UBERON:0000997	99.08	gold quality
cranial nerve II	UBERON:0000941	99.07	gold quality
superficial temporal artery	UBERON:0001614	99.07	gold quality
epithelium of mammary gland	UBERON:0003244	99.06	gold quality
putamen	UBERON:0001874	99.02	gold quality
epithelium of nasopharynx	UBERON:0001951	99.01	gold quality
tibia	UBERON:0000979	98.99	gold quality
cingulate cortex	UBERON:0003027	98.96	gold quality
amygdala	UBERON:0001876	98.95	gold quality
cauda epididymis	UBERON:0004360	98.95	gold quality
anterior cingulate cortex	UBERON:0009835	98.95	gold quality
forebrain	UBERON:0001890	98.94	gold quality
midbrain	UBERON:0001891	98.94	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.94	gold quality
brain	UBERON:0000955	98.92	gold quality
central nervous system	UBERON:0001017	98.92	gold quality
skin of hip	UBERON:0001554	98.92	gold quality
hypothalamus	UBERON:0001898	98.87	gold quality
substantia nigra	UBERON:0002038	98.87	gold quality
heart right ventricle	UBERON:0002080	98.87	gold quality
paraflocculus	UBERON:0005351	98.84	gold quality
spinal cord	UBERON:0002240	98.82	gold quality
upper leg skin	UBERON:0004262	98.80	gold quality
myocardium	UBERON:0002349	98.77	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.74	gold quality
oral cavity	UBERON:0000167	98.73	gold quality
mucosa of urinary bladder	UBERON:0001259	98.73	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.72	gold quality
amniotic fluid	UBERON:0000173	98.70	gold quality
middle frontal gyrus	UBERON:0002702	98.70	gold quality
inferior olivary complex	UBERON:0002127	98.69	gold quality
synovial joint	UBERON:0002217	98.68	gold quality
nephron tubule	UBERON:0001231	98.66	gold quality
cartilage tissue	UBERON:0002418	98.66	gold quality
globus pallidus	UBERON:0001875	98.64	gold quality
blood vessel layer	UBERON:0004797	98.63	gold quality
Brodmann (1909) area 10	UBERON:0013541	98.57	gold quality
vena cava	UBERON:0004087	98.56	gold quality
upper arm skin	UBERON:0004263	98.52	gold quality
lower lobe of lung	UBERON:0008949	98.49	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	81.57
E-HCAD-35	yes	51.35
E-HCAD-11	yes	38.00
E-GEOD-134144	yes	32.95
E-MTAB-8410	yes	28.77
E-CURD-46	yes	16.54
E-MTAB-8142	yes	15.84
E-GEOD-70580	no	872.25
E-MTAB-6142	no	312.17
E-CURD-112	no	2.81
E-MTAB-9543	no	2.37
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	811.1
Choroid plexus	tissue	608.9
Caudate putamen	tissue	586.2
Postcentral gyrus	tissue	402.8
Hippocampal formation	tissue	363.4
Cerebral cortex	tissue	324.2	medium
Somatosensory cortex	tissue	324.2
Prefrontal cortex	tissue	314.0
Motor cortex	tissue	304.1
Thalamus	tissue	303.5
Occipital cortex	tissue	299.5
Putamen	tissue	285.6
Entorhinal cortex	tissue	279.0
Retrosplenial and cingulate cortex	tissue	278.7
Nucleus accumbens	tissue	275.7
Superior colliculi	tissue	270.4
Midbrain	tissue	269.6
Hippocampus	tissue	268.6	low
Temporal cortex	tissue	262.2
Cerebellum	tissue	255.7	medium
Pons	tissue	254.0
Retrosplenial cortex	tissue	250.5
Locus coeruleus	tissue	249.0
Basal ganglia	tissue	247.9	high
Corpus callosum	tissue	238.5
Ventral forebrain	tissue	232.0
Septum	tissue	229.4
Spinal cord	tissue	225.2
Substantia nigra	tissue	222.9
Insular cortex	tissue	220.9
Medulla oblongata	tissue	210.3
Hypothalamus	tissue	188.1
Heart muscle	tissue	184.8	not detected
Amygdala	tissue	180.2
Olfactory bulb	tissue	168.5
Retina	tissue	165.4
Periaqueductal gray	tissue	162.6
Ovary	tissue	143.3	not detected
Seminal vesicle	tissue	139.6	not detected
Prostate	tissue	137.0	not detected
Smooth muscle	tissue	131.5	not detected
Cervix	tissue	127.3	not detected
Kidney	tissue	123.9	not detected
Endometrium 1	tissue	117.5	not detected
Urinary bladder	tissue	116.6	not detected
Gallbladder	tissue	103.2	not detected
Breast	tissue	99.8	not detected
Skin 1	tissue	90.1	medium
Adrenal gland	tissue	87.3	low
Vagina	tissue	83.6	not detected
Thyroid gland	tissue	83.4	not detected
Adipose tissue	tissue	81.5	not detected
Pituitary gland	tissue	81.4
Bone marrow	tissue	78.9	not detected
Fallopian tube	tissue	75.2	not detected
Lung	tissue	74.7	low
Liver	tissue	74.5	not detected
Esophagus	tissue	74.4	not detected
Spleen	tissue	70.9	not detected
Tongue	tissue	69.1

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Perirhinal gyrus (383.1), Nucleus of the diagonal band (367.0), Habenula (364.0), Dorsal hippocampus (363.4), Olfactory area (357.3).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO3, HES1, HIF1A, MTF1, NFE2L2, NFKBIB, SP1, TP53, XBP1

miRNA regulators (miRDB)

Targeting PRNP by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 81 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488

Functional genomics

gnomAD constraint: pLI 0.000323, LOEUF 1.04, missense Z 1.44 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000379440 — one region, missense o/e 0.84.

Literature-anchored findings (GeneRIF, showing 40)

• fibrillogenesis of PrP (195-213) (PMID:11559357)
• Huntington disease phenocopy is a familial prion disease (PMID:11593450)
• sporadic–but not variant–Creutzfeldt-Jakob disease is associated with polymorphisms upstream of PRNP exon 1 (PMID:11704923)
• Three novel PrP mutants were examined employing this model system and compared with wild type as well as known mutant PrPs (PMID:11756421)
• Molecular dynamics simulations of wild-type and point mutation human prion protein at normal and elevated temperature. (PMID:11775001)
• colocalized with CBP70 in the nuclear compartment of NB4 cells (PMID:11787070)
• expressed on endothelial cells and is released during apoptosis on membrane microparticles in human plasma (PMID:11961239)
• All-trans retinoic acid down-regulates prion protein expression independently of granulocyte maturation. (PMID:11986958)
• Resting paroxysmal nocturnal hemoglobinuria (CD55(-)) platelets were devoid of surface PrPc, but activation of platelets resulted in the surface expression of PrPc. (PMID:12070046)
• PrP was detected on all major human blood cells types except eosinophils, but was not detected as ubiquitously or uniformly on major blood cell types of different animal species. (PMID:12084159)
• PRPc acquires Proteinase K resistance with structural rearrangement, which can be promoted by the presence of a PrP(Sc) template (PMID:12161431)
• Cell-surface prion protein interacts with glycosaminoglycans (PMID:12186633)
• Spontaneous mutations in the prion protein gene causing transmissible spongiform encephalopathy. (PMID:12205650)
• examined the kinetics of folding and unfolding reactions for the recombinant human prion protein C-terminal fragment 90-231; data provide clear evidence for the population of an intermediate on the refolding pathway of the prion protein (PMID:12356762)
• PrP(C) transfer required the GPI anchor and direct cell to cell contact (PMID:12359724)
• Cellular stress up-regulates both the transcription and translation of PrP through interaction with the HSEs on the PrP gene promoter, resulting in an increase in protein synthesis. (PMID:12392052)
• PRNP missense mutations causing familial Creutzfeldt-Jakob disease recapitulate conserved residues in Doppel: a case of molecular mimicry? (PMID:12459456)
• CD34+ cells from paroxysmal nocturnal hemoglobinuria (PNH) patients are deficient in surface expression of cellular prion protein (PrPc). This may be a suitable system to explore the function of membrane PrP(c) in the hematopoietic system. (PMID:12543108)
• NMR structure of the globular domain with residues 121-230 of a variant human prion protein with two disulfide bonds, hPrP(M166C/E221C), shows the same global fold as wild-type hPrP(121-230) (PMID:12547204)
• detail the schematic construction of PrP(Sc) monomeric and dimeric models (PMID:12568340)
• Mutant PrP is associated with neurodegeneration in prion diseases. (PMID:12590162)
• Review. PrPC is a membrane glycoprotein expressed by most tissues and is attached on the cell membrane by a glycosyl-phosphatidylinositol anchor which would be consistent with roles in cell adhesion, ligand uptake, or transmembrane signaling. (PMID:12645301)
• has different biological properties than linked GPI-anchored protein DAF (PMID:12659837)
• Polymorphism of the codon 129 of the prion protein (PrP) gene and neuropathology of cerebral ageing. (PMID:12679875)
• Neuropathological features of a case with schizophrenia and prion protein gene P102L mutation before onset of Gerstmann-Straussler-Scheinker disease. (PMID:12682740)
• Abbreviated incubation times for human prions in mice expressing a chimeric mouse-human prion protein transgene. (PMID:12684540)
• Kuru imposed strong balancing selection on the Fore, essentially eliminating PRNP 129 homozygotes; worldwide PRNP haplotype diversity and coding allele frequencies suggest strong balancing selection at this locus occurred during evolution of modern humans (PMID:12690204)
• observed that PrP106-126 is a chemoattractant for monocyte-derived immature but not mature dendritic cells; results suggest transactivation of sphingosine-1-phosphate-dependent cell motility by prion protein (PMID:12692258)
• findings highlight the role of PrP in copper homeostasis and hint at its possible role as a modulator of synapses regulated by this trace metal (PMID:12694397)
• plasmin cleaves PrP(c) in vitro and the liberated NH(2)-terminal fragment accelerates plasminogen activation (PMID:12719777)
• The 129 codon polymorphism of the prion protein gene influences earlier cognitive performance in Down syndrome subjects. (PMID:12796830)
• a specific prion protein fragment has a role in disulfide stability by retarding the rate of fibril formation (PMID:12805563)
• proteinase K-resistant C-terminal fragments of PrP are identified in Creutzfeldt-Jakob disease brains (PMID:12917418)
• endoplasmic reticulum-associated degradation PrP is not converted naturally into a form reminiscent of scrapie PrP and that PrP located in the cytosol retains its protective function against Bax (PMID:12917444)
• interactions between small, highly structured RNAs and human recombinant prion protein (PrP) suggest possible roles of RNAs in the modulation of PrP structure and perhaps disease development (PMID:12946346)
• interconversion of helix 1 of the prion protein is rather representing a barrier than a nucleus for the PrPC–>PrPSc conversion (PMID:12952977)
• the intrinsic properties of PrP-(82-146) are dependent upon the integrity of the C-terminal region and account for the massive deposition of PrP amyloid in GSS (PMID:12970341)
• spontaneous conversion of the recombinant polypeptide corresponding to the Y145Stop variant (huPrP23-144) from a monomeric unordered state to a fibrillar form (PMID:14519851)
• PrPc has a role in the signaling of cell-cell contacts in epithelial cells (PMID:14576159)
• association of a common genetic variation in the prion protein gene with cognitive performance (PMID:14593432)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prnp	ENSMUSG00000079037
rattus_norvegicus	Prnp	ENSRNOG00000021259

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97769) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 113 distinct phenotype terms.

Mouse phenotype (MP)	Records
ataxia	10
decreased susceptibility to prion infection	8
premature death	7
increased susceptibility to prion infection	7
astrocytosis	6
spongiform encephalopathy	5
gliosis	4
neuron degeneration	4
kyphosis	3
tremors	3
decreased locomotor activity	3
impaired coordination	3
abnormal brain morphology	3
abnormal nervous system morphology	3
lethargy	3
hindlimb paralysis	2
abnormal thalamus morphology	2
abnormal cerebellum morphology	2
weight loss	2
abnormal gait	2
abnormal sleep pattern	2
limb grasping	2
male infertility	2
neurodegeneration	2
abnormal sciatic nerve morphology	2

+88 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	F7VJQ2	97.0%	Diamond
Ovis aries	F7VJQ3	97.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PRNT	ncRNA	149830
PRND	protein-coding	23627
RASSF2	protein-coding	9770

Protein

Protein identifiers

Alternative prion protein — F7VJQ1 (reviewed: F7VJQ1, P04156)

Alternative names: AltPrP

All UniProt accessions (4): A2A2V1, P04156, Q53YK7, X6RKS3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Mitochondrion outer membrane.

Tissue specificity. Detected in brain homogenate, primary neurons, and peripheral blood mononuclear cells (at protein level).

Induction. Up-regulated by endoplasmic reticulum stress and proteasomal inhibition.

Miscellaneous. This protein is produced by a bicistronic gene which also produces the major prion protein/PRNP from an overlapping reading frame. The alternative prion protein/AltPrP and PRNP (AC P04156) have no apparent direct functional relation since a mutation that removes the start codon of the AltPrP has no apparent effect on the biology of PRNP. In mouse and hamster, the alternative initiation AUG codon is absent and is replaced by a GUG codon.

Isoforms (2)

UniProt ID	Names	Canonical?
F7VJQ1-1	3, AltPrP	yes
P04156-1	1, PrP

RefSeq proteins (6): NP_000302, NP_001073590, NP_001073591, NP_001073592, NP_001258490, NP_898902 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000817	Prion	Family
IPR020949	Prion_copper_b_octapeptide	Repeat
IPR022416	Prion/Doppel_prot_b-ribbon_dom	Domain
IPR025860	Prion_N	Domain
IPR036924	Prion/Doppel_b-ribbon_dom_sf	Homologous_superfamily

Pfam: PF00377, PF03991, PF11587

UniProt features (91 total): sequence variant 27, strand 17, binding site 12, helix 7, turn 6, repeat 5, region of interest 4, sequence conflict 3, chain 2, glycosylation site 2, transmembrane region 1, signal peptide 1, compositionally biased region 1, propeptide 1, lipid moiety-binding region 1, disulfide bond 1

Structure

Experimental structures (PDB)

showing 30 of 70 structures by resolution:

PDB	Title	Method	Resolution (Å)
2OL9	Peptide corresponding to residues 170-175 of human prion	X-RAY DIFFRACTION	0.85
7RVE	Segment from the S170N mutant of the human prion protein 168-176 EYNNQNNFV	ELECTRON CRYSTALLOGRAPHY	0.85
7RVJ	Segment from the human prion protein 169-175 YSNQNNF	ELECTRON CRYSTALLOGRAPHY	1
7RVK	Segment from Y169G mutant of the human prion protein 169-175 GSNQNNF	ELECTRON CRYSTALLOGRAPHY	1
7RVL	Segment from the Y169F mutant of the human prion protein 168-176 EFSNQNNFV	ELECTRON CRYSTALLOGRAPHY	1
7RVC	Segment from the human prion protein 168-176 EYSNQNNFV	ELECTRON CRYSTALLOGRAPHY	1
3MD4	Prion peptide	X-RAY DIFFRACTION	1.15
3MD5	Prion peptide	X-RAY DIFFRACTION	1.4
4E1H	Fragment of human prion protein	X-RAY DIFFRACTION	1.4
6PQA	GAVVGG segment 119-124 from human prion	X-RAY DIFFRACTION	1.46
4KML	Probing the N-terminal beta-sheet conversion in the crystal structure of the full-length …	X-RAY DIFFRACTION	1.5
4N9O	Probing the N-terminal beta-sheet conversion in the crystal structure of the human prion …	X-RAY DIFFRACTION	1.5
6PQ5	AGAAAA segment 113-118 from human prion	X-RAY DIFFRACTION	1.5
3NHC	GYMLGS segment 127-132 from human prion with M129	X-RAY DIFFRACTION	1.57
3HAK	Human prion protein variant V129	X-RAY DIFFRACTION	1.8
3HEQ	Human prion protein variant D178N with M129	X-RAY DIFFRACTION	1.8
3NVF	IIHFGS segment 138-143 from human prion	X-RAY DIFFRACTION	1.8
3HER	Human prion protein variant F198S with V129	X-RAY DIFFRACTION	1.85
3NHD	GYVLGS segment 127-132 from human prion with V129	X-RAY DIFFRACTION	1.92
1I4M	Crystal structure of the human prion protein reveals a mechanism for oligomerization	X-RAY DIFFRACTION	2
3HES	Human prion protein variant F198S with M129	X-RAY DIFFRACTION	2
3HJX	Human prion protein variant D178N with V129	X-RAY DIFFRACTION	2
4E1I	Fragment of human prion protein	X-RAY DIFFRACTION	2.03
3HAF	Human prion protein variant V129 domain swapped dimer	X-RAY DIFFRACTION	2.26
6SV2	Human prion protein (PrP) fragment 119-231 (G127V M129 variant) complexed to ICSM 18 …	X-RAY DIFFRACTION	2.3
6DU9	Crystal Structure of Human Prion Protein 90-231	X-RAY DIFFRACTION	2.33
4DGI	Structure of POM1 FAB fragment complexed with human PrPc Fragment 120-230	X-RAY DIFFRACTION	2.4
6SUZ	Human prion protein (PrP) fragment 119-231 (G127V V129 variant) complexed to ICSM 18 …	X-RAY DIFFRACTION	2.5
6LNI	Cryo-EM structure of amyloid fibril formed by full-length human prion protein	ELECTRON MICROSCOPY	2.7
7RL4	Cryo-EM structure of human PrP23-144 amyloid fibrils	ELECTRON MICROSCOPY	2.86

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-F7VJQ1-F1	68.18	0.00
AF-P04156-F1	66.12	0.09

Antibody-complex structures (SAbDab)

6 antibodies co-crystallized with this protein: 2W9E, 4DGI, 4KML, 4N9O, 6SUZ, 6SV2

Human Protein Atlas

Protein class: CD markers, Transporters, Transporter channels and pores, Predicted membrane proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nuclear membrane; vesicles

Antibody reliability (HPA): IH enhanced · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (12)

Position	Role
61	Cu(2+)
62	Cu(2+)
63	Cu(2+)
69	Cu(2+)
70	Cu(2+)
71	Cu(2+)
77	Cu(2+)
78	Cu(2+)
79	Cu(2+)
85	Cu(2+)
86	Cu(2+)
87	Cu(2+)

Post-translational modifications (1)

Type	Positions
Gpi-anchor amidated serine	230

Disulfide bonds (1)

Type	Positions
Disulfide bond	179–214

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	181, 197

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-422475	Axon guidance	—
R-HSA-1266738	Developmental Biology	—
R-HSA-9609523	Insertion of tail-anchored proteins into the endoplasmic reticulum membrane	electronic
R-HSA-375165	NCAM signaling for neurite out-growth	—
R-HSA-419037	NCAM1 interactions	electronic
R-HSA-9675108	Nervous system development	—
R-HSA-9609507	Protein localization	—

MSigDB gene sets: 967 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_MEMORY, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, REACTOME_BIOLOGICAL_OXIDATIONS, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION

GO Biological Process (35): negative regulation of transcription by RNA polymerase II (GO:0000122), intracellular copper ion homeostasis (GO:0006878), response to oxidative stress (GO:0006979), learning or memory (GO:0007611), long-term memory (GO:0007616), negative regulation of protein processing (GO:0010955), protein destabilization (GO:0031648), negative regulation of type II interferon production (GO:0032689), negative regulation of interleukin-17 production (GO:0032700), negative regulation of interleukin-2 production (GO:0032703), intracellular signal transduction (GO:0035556), negative regulation of apoptotic process (GO:0043066), positive regulation of neuron apoptotic process (GO:0043525), negative regulation of activated T cell proliferation (GO:0046007), response to cadmium ion (GO:0046686), positive regulation of calcium-mediated signaling (GO:0050850), negative regulation of T cell receptor signaling pathway (GO:0050860), protein homooligomerization (GO:0051260), regulation of cell cycle (GO:0051726), negative regulation of calcineurin-NFAT signaling cascade (GO:0070885), cellular response to copper ion (GO:0071280), positive regulation of protein targeting to membrane (GO:0090314), dendritic spine maintenance (GO:0097062), negative regulation of long-term synaptic potentiation (GO:1900272), regulation of glutamate receptor signaling pathway (GO:1900449), positive regulation of glutamate receptor signaling pathway (GO:1900451), negative regulation of amyloid-beta formation (GO:1902430), negative regulation of dendritic spine maintenance (GO:1902951), negative regulation of amyloid precursor protein catabolic process (GO:1902992), positive regulation of protein localization to plasma membrane (GO:1903078), response to amyloid-beta (GO:1904645), cellular response to amyloid-beta (GO:1904646), regulation of calcium ion import across plasma membrane (GO:1905664), neuron projection maintenance (GO:1990535), response to copper ion (GO:0046688)

GO Molecular Function (22): amyloid-beta binding (GO:0001540), protease binding (GO:0002020), copper ion binding (GO:0005507), lamin binding (GO:0005521), glycosaminoglycan binding (GO:0005539), microtubule binding (GO:0008017), tubulin binding (GO:0015631), aspartic-type endopeptidase inhibitor activity (GO:0019828), type 5 metabotropic glutamate receptor binding (GO:0031802), signaling receptor activity (GO:0038023), identical protein binding (GO:0042802), ATP-dependent protein binding (GO:0043008), transmembrane transporter binding (GO:0044325), protein-containing complex binding (GO:0044877), protein-folding chaperone binding (GO:0051087), molecular adaptor activity (GO:0060090), molecular function activator activity (GO:0140677), molecular condensate scaffold activity (GO:0140693), cupric ion binding (GO:1903135), cuprous ion binding (GO:1903136), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (18): mitochondrial outer membrane (GO:0005741), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), postsynaptic density (GO:0014069), inclusion body (GO:0016234), extrinsic component of membrane (GO:0019898), dendrite (GO:0030425), terminal bouton (GO:0043195), membrane raft (GO:0045121), extracellular exosome (GO:0070062), postsynapse (GO:0098794), membrane (GO:0016020), side of membrane (GO:0098552)

Reactome top-level categories

5 top-level categories:

Category	Pathways
NCAM signaling for neurite out-growth	1
Protein localization	1
Axon guidance	1
Nervous system development	1
Developmental Biology	1

GO top-level categories

showing 60 of 82 GO namespaces:

Category	Terms
cellular anatomical structure	7
protein binding	5
negative regulation of cytokine production	3
intracellular anatomical structure	3
cytoplasm	3
membrane	3
binding	2
copper ion binding	2
endomembrane system	2
intracellular membrane-bounded organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
intracellular monoatomic cation homeostasis	1
copper ion homeostasis	1
response to stress	1
behavior	1
cognition	1
memory	1
protein processing	1
negative regulation of proteolysis	1
regulation of protein processing	1
negative regulation of protein maturation	1
regulation of protein stability	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-17 production	1
regulation of interleukin-17 production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
signal transduction	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
positive regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
negative regulation of T cell proliferation	1
regulation of activated T cell proliferation	1
activated T cell proliferation	1
response to metal ion	1
calcium-mediated signaling	1
regulation of calcium-mediated signaling	1
positive regulation of intracellular signal transduction	1
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
negative regulation of antigen receptor-mediated signaling pathway	1
protein complex oligomerization	1
cell cycle	1
regulation of cellular process	1
calcineurin-NFAT signaling cascade	1
regulation of calcineurin-NFAT signaling cascade	1
negative regulation of calcineurin-mediated signaling	1
peptide binding	1
enzyme binding	1
transition metal ion binding	1
carbohydrate derivative binding	1
tubulin binding	1
cytoskeletal protein binding	1
aspartic-type endopeptidase activity	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 23 of 75 annotations. The rest are phylogenetic / computational / electronic (IEA).

23 experimentally-supported GO terms:

GO term	NS	Evidence
cellular response to amyloid-beta	BP	genetic interaction
cellular response to copper ion	BP	direct assay
intracellular signal transduction	BP	direct assay
positive regulation of calcium-mediated signaling	BP	genetic interaction
positive regulation of glutamate receptor signaling pathway	BP	genetic interaction
positive regulation of neuron apoptotic process	BP	mutant phenotype
protein destabilization	BP	mutant phenotype
cell surface	CC	direct assay
dendrite	CC	direct assay
extracellular exosome	CC	high-throughput assay
inclusion body	CC	mutant phenotype
membrane raft	CC	direct assay
mitochondrial outer membrane	CC	direct assay
plasma membrane	CC	direct assay
amyloid-beta binding	MF	direct assay
copper ion binding	MF	direct assay
cuprous ion binding	MF	mutant phenotype
identical protein binding	MF	physical interaction
microtubule binding	MF	direct assay
molecular adaptor activity	MF	direct assay
molecular condensate scaffold activity	MF	direct assay
protein-containing complex binding	MF	physical interaction
tubulin binding	MF	direct assay

Protein interactions and networks

IntAct

BioGRID (2,595 interactions; top human partners by supporting records in a sample of 600 records): CBL (Affinity Capture-Western; 4 records), NCAM1 (Reconstituted Complex; 4 records), CYLD (Affinity Capture-MS; 3 records), F2RL1 (Affinity Capture-Western; 3 records), FZD7 (Affinity Capture-Western; 3 records), GRM5 (Affinity Capture-Western; 3 records), HAX1 (Two-hybrid; 3 records), RPSA (Affinity Capture-MS; 3 records), STIP1 (Affinity Capture-MS; 3 records), ADRB2 (FRET; 2 records), ARF1 (Affinity Capture-Western; 2 records), ATP6V1B2 (Two-hybrid; 2 records), CCR1 (FRET; 2 records), DNAJA2 (Affinity Capture-MS; 2 records), IGF1R (Affinity Capture-Western; 2 records)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
“ER stress”	up-regulates	PRNP
CDK5	“up-regulates quantity”	PRNP	phosphorylation

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
ADGRG6	ligand

Disease & clinical

Genetic variants

Variant evidence for PRNP: 203 ClinVar records (25 pathogenic / likely pathogenic); 10 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

203 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	8
Uncertain significance	94
Likely benign	37
Benign	19

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 25 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
13398	NM_000311.5(PRNP):c.598G>A (p.Glu200Lys)	Pathogenic	criteria provided, multiple submitters, no conflicts	13
13395	NM_000311.5(PRNP):c.305C>T (p.Pro102Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	12
13401	NM_000311.5(PRNP):c.593T>C (p.Phe198Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
13396	NM_000311.5(PRNP):c.350C>T (p.Ala117Val)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
13407	NM_000311.5(PRNP):c.547A>G (p.Thr183Ala)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
13402	NM_000311.5(PRNP):c.650A>G (p.Gln217Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1507942	NM_000311.5(PRNP):c.443G>A (p.Arg148His)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2138330	NM_000311.5(PRNP):c.563C>G (p.Thr188Arg)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
13404	NM_000311.5(PRNP):c.314C>T (p.Pro105Leu)	Pathogenic	criteria provided, single submitter	2
21148	NM_000311.5(PRNP):c.478C>T (p.Gln160Ter)	Pathogenic	criteria provided, single submitter	2
689659	NM_000311.5(PRNP):c.227_228insTCATGGTGGTGGCTGGGGGCAGCCTCATGGTGGTGGCTGGGGGCAGCCCCATGGTGGTGGCTGGGGACAGCCTCATGGTGGTGGCTGGGGGCAGCCTCATGGTGGTGGCTGGGGGCAGCCTCATGGTGGTGGCTGGGGGCAGCCTCATGGTGGTGGCTGGGGGCAGCCTCATGGTGGTGGCTGGGGGCAGCC (p.Gln91_Gly92insProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGlnProHisGlyGlyGlyTrpGlyGln)	Pathogenic	criteria provided, single submitter	1
2815837	NM_000311.5(PRNP):c.350_351inv (p.Ala117Val)	Pathogenic	criteria provided, single submitter	1
88926	NM_000311.5(PRNP):c.678C>A (p.Tyr226Ter)	Likely pathogenic	criteria provided, single submitter	2
1334094	NM_000311.5(PRNP):c.392G>A (p.Gly131Glu)	Likely pathogenic	criteria provided, single submitter	1
4819098	NM_000311.5(PRNP):c.353C>T (p.Ala118Val)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore PRNP’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 19 predictions of 187):

Position(s)	Effect	Δscore	Sites
20:4686513–4686514	donor_loss	0.9900	5
20:4691890	acceptor_gain	0.9800
20:4699209–4699210	acceptor_loss	0.9700	6
20:4686514	donor_loss	0.9500
20:4691890	acceptor_gain	0.9500
20:4691895	acceptor_gain	0.9400
20:4686510	donor_loss	0.9300
20:4686512	donor_loss	0.9100
20:4699208	acceptor_loss	0.9000
20:4686512	donor_loss	0.8900

AlphaMissense

754 missense substitutions predicted likely pathogenic (of 1,678 scored), across 202 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M213	9	0.851	0.981
F141	8	0.977	0.997
F175	8	0.976	0.999
D202	8	0.961	0.997
D178	8	0.937	0.989
N153	8	0.921	0.992
D147	8	0.892	0.984
C179	7	0.999	1.000
C214	7	0.998	1.000
H187	7	0.908	0.993
N181	7	0.895	0.972
M206	7	0.890	0.958
E146	7	0.885	0.971
N197	7	0.771	0.928
P158	6	0.980	0.995
V161	6	0.976	0.991
T183	6	0.969	0.999
G123	6	0.929	0.991
V176	6	0.922	0.976
P137	6	0.918	0.965

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	4.78e-06
Lung Squamous Cell Carcinoma (validation)	unfavorable	0.000281
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000302

Disease associations

OMIM: gene MIM:176640 | disease phenotypes: MIM:137440, MIM:123400, MIM:603218, MIM:606688, MIM:245300, MIM:600072

GenCC curated gene-disease

6 curated gene-disease records:

Disease	Classification	Inheritance	Records
Gerstmann-Straussler-Scheinker syndrome	Definitive	Autosomal dominant	3
inherited Creutzfeldt-Jakob disease	Strong	Autosomal dominant	3
Huntington disease-like 1	Strong	Autosomal dominant	2
familial Alzheimer-like prion disease	Supportive	Autosomal dominant
PrP systemic amyloidosis	Supportive	Autosomal dominant
fatal familial insomnia	Supportive	Autosomal dominant

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (15 panels, 14 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

15 panels:

Panel	Rating
Adult-onset neurological disorders	green
Ataxia and cerebellar anomalies - childhood onset	green
Dystonia, chorea or related movement disorder, adult onset	green
Early onset dementia (encompassing fronto-temporal dementia and prion disease)	green
Hereditary ataxia	green
Hereditary ataxia and cerebellar anomalies, childhood onset	green
Hereditary ataxia, adult onset	green
Hereditary neuropathy	green
Hereditary neuropathy or pain disorder	green
Hereditary spastic paraplegia, adult onset	green
Leukodystrophy, adult onset	green
Neurodegenerative disorders, adult onset	green
Pain syndromes	green
Structural basal ganglia disorders	green
Familial dysautonomia	amber

Mondo (9): Gerstmann-Straussler-Scheinker syndrome (MONDO:0007656), inherited Creutzfeldt-Jakob disease (MONDO:0007403), Huntington disease-like 1 (MONDO:0011299), spongiform encephalopathy with neuropsychiatric features (MONDO:0011703), kuru, susceptibility to (MONDO:0009500), fatal familial insomnia (MONDO:0010808), congenital portosystemic shunt (MONDO:0018811), familial Alzheimer-like prion disease (MONDO:0017233), PrP systemic amyloidosis (MONDO:0018339)

Orphanet (9): Gerstmann-Straussler-Scheinker syndrome (Orphanet:356), Huntington disease-like 1 (Orphanet:157941), Sporadic Creutzfeldt-Jakob disease (Orphanet:204), Inherited human prion disease (Orphanet:280400), Inherited Creutzfeldt-Jakob disease (Orphanet:282166), Acquired Creutzfeldt-Jakob disease (Orphanet:454700), Kuru (Orphanet:454745), Fatal familial insomnia (Orphanet:466), Congenital portosystemic shunt (Orphanet:480531)

HPO phenotypes

showing 60 of 155 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000016	Urinary retention
HP:0000298	Mask-like facies
HP:0000496	Abnormality of eye movement
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment
HP:0000514	Slow saccadic eye movements
HP:0000570	Abnormal saccadic eye movements
HP:0000605	Supranuclear gaze palsy
HP:0000617	Abnormality of ocular smooth pursuit
HP:0000639	Nystagmus
HP:0000651	Diplopia
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000710	Hyperorality
HP:0000711	Restlessness
HP:0000712	Emotional lability
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000726	Dementia
HP:0000736	Short attention span
HP:0000737	Irritability
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000746	Delusion
HP:0000750	Delayed speech and language development
HP:0000751	Personality changes
HP:0000822	Hypertension
HP:0000975	Hyperhidrosis
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001262	Excessive daytime somnolence
HP:0001268	Mental deterioration
HP:0001269	Hemiparesis
HP:0001272	Cerebellar atrophy
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001289	Confusion
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001300	Parkinsonism
HP:0001310	Dysmetria
HP:0001315	Diminished deep tendon reflex
HP:0001317	Abnormal cerebellum morphology
HP:0001324	Muscle weakness
HP:0001328	Specific learning disability
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001350	Slurred speech
HP:0001649	Tachycardia
HP:0001824	Weight loss
HP:0001945	Fever
HP:0002015	Dysphagia
HP:0002019	Constipation
HP:0002062	Abnormal pyramidal tract morphology
HP:0002063	Rigidity

GWAS associations

10 associations:

Study	Trait	p-value
GCST000294_2	Creutzfeldt-Jakob disease	2e-21
GCST001334_1	Creutzfeldt-Jakob disease (variant)	3e-18
GCST90001389_1	Creutzfeldt-Jakob disease (sporadic)	1e-16
GCST002878_1	Creutzfeldt-Jakob disease (sporadic)	8e-9
GCST007948_1	KANNO antigen negativity	3e-8
GCST001334_2	Creutzfeldt-Jakob disease (variant)	5e-7
GCST001366_1	Prion diseases	7e-7
GCST000693_6	Platelet aggregation	2e-6
GCST004502_2	Waist circumference adjusted for BMI (smoking interaction)	2e-6
GCST004501_103	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	3e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:1000656	sporadic Creutzfeld Jacob disease
EFO:0004318	smoking behavior
EFO:0007789	BMI-adjusted waist circumference
EFO:0009949	KANNO antigen measurement

MeSH disease descriptors

4 disease descriptors:

Descriptor	Name	Tree numbers
D034062	Insomnia, Fatal Familial	C01.207.800.392; C10.228.228.800.392; C10.574.843.512; C10.886.425.800.800.400
C535800	Amyloidosis, Cerebral, with Spongiform Encephalopathy *(supp.)*
C566398	Huntington Disease-Like 1 *(supp.)*
C564678	Spongiform Encephalopathy with Neuropsychiatric Features *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

PubChem BioAssay actives

7 with measured affinity, of 161 total; 7 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-N-(6-chloro-2-methoxyacridin-9-yl)-1-N,1-N-diethylpentane-1,4-diamine	161627: Half maximal inhibition of Prion protein PrPsc formation was assayed in ScN2a cells	ec50	0.3000	uM
Chlorpromazine	161627: Half maximal inhibition of Prion protein PrPsc formation was assayed in ScN2a cells	ec50	2.0000	uM
Chloroquine	161627: Half maximal inhibition of Prion protein PrPsc formation was assayed in ScN2a cells	ec50	4.0000	uM
N,N-dimethyl-3-phenothiazin-10-ylpropan-1-amine	161627: Half maximal inhibition of Prion protein PrPsc formation was assayed in ScN2a cells	ec50	5.0000	uM
Acepromazine	161627: Half maximal inhibition of Prion protein PrPsc formation was assayed in ScN2a cells	ec50	5.0000	uM
Promethazine	161627: Half maximal inhibition of Prion protein PrPsc formation was assayed in ScN2a cells	ec50	8.0000	uM
Imipramine	161627: Half maximal inhibition of Prion protein PrPsc formation was assayed in ScN2a cells	ec50	10.0000	uM

CTD chemical–gene interactions

112 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Copper	affects cotreatment, increases reaction, increases response to substance, affects binding, increases activity (+6 more)	15
Valproic Acid	affects cotreatment, increases expression	8
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance, increases expression	7
bisphenol A	affects expression, decreases expression, increases expression	4
Tretinoin	decreases expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Acetaminophen	increases expression	3
Air Pollutants	affects expression, increases abundance, increases expression	3
Estradiol	affects expression, affects cotreatment, increases expression	3
Tobacco Smoke Pollution	increases expression, affects expression	3
Copper Sulfate	increases expression, affects localization, increases uptake, decreases reaction, affects binding	3
methylmercuric chloride	increases expression	2
perfluorooctanoic acid	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Aerosols	increases expression	2
Oxygen	increases expression, decreases expression, decreases reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
Particulate Matter	increases expression, affects expression, increases abundance	2
graphene oxide	decreases expression	1
ethylbenzene	increases expression	1
methylselenic acid	increases expression	1
3,4-dichloroaniline	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1

Cellosaurus cell lines

22 cell lines: 18 induced pluripotent stem cell, 3 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0N79	AG09950	Transformed cell line	Male
CVCL_D2WC	CJD2	Induced pluripotent stem cell	Female
CVCL_D3BK	CJD2CR	Induced pluripotent stem cell	Female
CVCL_D3BL	CJD13	Induced pluripotent stem cell	Female
CVCL_D3BM	CJD13CR	Induced pluripotent stem cell	Female
CVCL_D3BP	CJD29	Induced pluripotent stem cell	Female
CVCL_D3BQ	CJD3	Induced pluripotent stem cell	Female
CVCL_D3BR	CJD4	Induced pluripotent stem cell	Male
CVCL_D3BS	CJD40	Induced pluripotent stem cell	Female
CVCL_D3BT	CJD5	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00165763	Phase 4	COMPLETED	Efficacy and Safety of Donepezil Hydrochloride (Aricept) in Vascular Dementia
NCT00847860	Phase 4	COMPLETED	Cilostazol Verse Asprin for Vascular Dementia in Poststroke Patients With White Matter Lesions
NCT00947531	Phase 4	COMPLETED	A Clinical Trial to Evaluate the Safety and Efficacy of 20 ml Cerebrolysin in Patients With Vascular Dementia
NCT00950430	Phase 4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT00391261	Phase 4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	Phase 4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	Phase 4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	Phase 4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	Phase 4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	Phase 4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	Phase 4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	Phase 4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	Phase 4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	Phase 4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	Phase 4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	Phase 4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	Phase 4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	Phase 4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	Phase 4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	Phase 4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	Phase 4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	Phase 4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	Phase 4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	Phase 4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	Phase 4	RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT07770152	Phase 4	NOT_YET_RECRUITING	Semaglutide in Youth With Autism Spectrum Disorder
NCT07482085	Phase 3	RECRUITING	Efavirenz for the Treatment of Creutzfeldt-Jakob Disease
NCT00099216	Phase 3	COMPLETED	Efficacy and Safety of Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00130338	Phase 3	COMPLETED	Rivastigmine Capsules in Patients With Probable Vascular Dementia
NCT00209456	Phase 3	COMPLETED	Dopamine Transporter Scintigraphy Imaging (DAT-Imaging) in Patients With Lewy Body Dementia
NCT00249158	Phase 3	COMPLETED	A Study of the Effectiveness and Safety of Risperidone in the Treatment of Behavioral Disturbances in Patients With Dementia
NCT00261573	Phase 3	COMPLETED	A Study of the Safety and Effectiveness of Galantamine Versus Placebo in the Treatment of Patients With Vascular Dementia or Mixed Dementia
NCT00621647	Phase 3	COMPLETED	Seroquel- Agitation Associated With Dementia
NCT02453932	Phase 3	COMPLETED	Efficacy and Safety of Tianzhi Granule in Mild to Moderate Vascular Dementia
NCT03682185	Phase 3	COMPLETED	The Healthy Patterns Sleep Study
NCT03789760	Phase 3	COMPLETED	The Clinical Trial of Chinese Herbal Medicine (SaiLuoTong) Capsule
NCT03804229	Phase 3	ACTIVE_NOT_RECRUITING	Efficacy and Safety of Butylphthalide Soft Capsule for the Treatment of Vascular Dementia
NCT03986424	Phase 3	COMPLETED	Local Study of Akatinol Memantine in VaD in Russia
NCT04552041	Phase 3	COMPLETED	Prospekta in the Treatment of Cognitive, Behavioral and Psychiatric Disorders in Patients With Vascular Dementia.
NCT01302964	Phase 3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	Phase 3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	Phase 3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	Phase 3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	Phase 3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	Phase 3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	Phase 3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	Phase 3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	Phase 3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	Phase 3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	Phase 3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	Phase 3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	Phase 3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	Phase 3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	Phase 3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	Phase 3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	Phase 3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	Phase 3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	Phase 3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder
NCT06333964	Phase 3	COMPLETED	A Study to Evaluate the Efficacy and Safety of AST-001 in ASD Children
NCT07257939	Phase 3	NOT_YET_RECRUITING	NTI164 in Autism Spectrum Disorder

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PRNP across ~30M SureChEMBL compounds — explore on Sugi Predict.