PRNP prion protein (Kanno blood group) [Homo sapiens (human)] - Gene

Summary

Official Symbol: PRNPprovided by HGNC
Official Full Name: prion protein (Kanno blood group)provided by HGNC
Primary source: HGNC:HGNC:9449
See related: Ensembl:ENSG00000171867 MIM:176640; AllianceGenome:HGNC:9449
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CJD; GSS; PrP; ASCR; KURU; PRIP; PrPc; CD230; AltPrP; p27-30; PrP27-30; PrP33-35C
Summary: 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. [provided by RefSeq, Nov 2014]
Expression: Ubiquitous expression in brain (RPKM 148.7), ovary (RPKM 52.6) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 20p13

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	20	NC_000020.11 (4686456..4701588)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	20	NC_060944.1 (4725692..4740800)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (4667102..4682234)

Chromosome 20 - NC_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Copper binding alters the core structure of amyloid fibrils formed by Y145Stop human prion protein.
Title: Copper binding alters the core structure of amyloid fibrils formed by Y145Stop human prion protein.
Cellular prion protein acts as mediator of amyloid beta uptake by caveolin-1 causing cellular dysfunctions in vitro and in vivo.
Title: Cellular prion protein acts as mediator of amyloid beta uptake by caveolin-1 causing cellular dysfunctions in vitro and in vivo.
Creatine Promotes Endometriosis by Inducing Ferroptosis Resistance via Suppression of PrP.
Title: Creatine Promotes Endometriosis by Inducing Ferroptosis Resistance via Suppression of PrP.
PrP[C] controls epithelial-to-mesenchymal transition in EGFR-mutated NSCLC: implications for TKI resistance and patient follow-up.
Title: PrP(C) controls epithelial-to-mesenchymal transition in EGFR-mutated NSCLC: implications for TKI resistance and patient follow-up.
Prion protein gene (PRNP) variation in German and Danish cervids.
Title: Prion protein gene (PRNP) variation in German and Danish cervids.
Neuropathologically directed profiling of PRNP somatic and germline variants in sporadic human prion disease.
Title: Neuropathologically directed profiling of PRNP somatic and germline variants in sporadic human prion disease.
Cellular Prion protein moonlights vascular smooth muscle cell fate: Surveilled by trophoblast cells.
Title: Cellular Prion protein moonlights vascular smooth muscle cell fate: Surveilled by trophoblast cells.
New Light on Prions: Putative Role of PrP[c] in Pathophysiology of Mood Disorders.
Title: New Light on Prions: Putative Role of PrP(c) in Pathophysiology of Mood Disorders.
Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas.
Title: Integrated transcriptomics uncovers an enhanced association between the prion protein gene expression and vesicle dynamics signatures in glioblastomas.
Excess PrP[C] inhibits muscle cell differentiation via miRNA-enhanced liquid-liquid phase separation implicated in myopathy.
Title: Excess PrP(C) inhibits muscle cell differentiation via miRNA-enhanced liquid-liquid phase separation implicated in myopathy.

Submit: New GeneRIF Correction See all GeneRIFs (676)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Fatal familial insomnia MedGen: C0206042 OMIM: 600072 GeneReviews: Genetic Prion Disease	not available
Gerstmann-Straussler-Scheinker syndrome MedGen: C0017495 OMIM: 137440 GeneReviews: Genetic Prion Disease	not available
Huntington disease-like 1 MedGen: C1864112 OMIM: 603218 GeneReviews: Genetic Prion Disease	not available
Inherited Creutzfeldt-Jakob disease MedGen: C0751254 OMIM: 123400 GeneReviews: Genetic Prion Disease	not available
Kuru, susceptibility to MedGen: C1855588 OMIM: 245300 GeneReviews: Genetic Prion Disease	not available
Spongiform encephalopathy with neuropsychiatric features MedGen: C1847650 OMIM: 606688 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analyses identifies seven loci associated with platelet aggregation in response to agonists. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide study links MTMR7 gene to variant Creutzfeldt-Jakob risk. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Pr55(Gag)	gag	Human cellular prion protein (CD230) colocalizes with HIV-1 Gag at the plasma membrane and at the virological synapse in infected T cells	PubMed
Tat	tat	HIV-1 Tat binds to a stem-loop structure in the mRNA of prion protein (PrP) that is similar to HIV-1 TAR RNA and infection of astrocytes with HIV-1 results in an increased level of PrP mRNA, suggesting Tat upregulates PrP expression	PubMed
nucleocapsid	gag	HIV-1 NC downregulates prion protein in HEK 293T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SGC44304 (e-PCR)
- UniSTS:2335

GDB:607655 (e-PCR)
- UniSTS:158256

PRNP-2 (e-PCR)
- UniSTS:254000

RH71030 (e-PCR)
- UniSTS:34672

D20S1014 (e-PCR)
- UniSTS:21619

PRNP (e-PCR)
- UniSTS:480133

GDB:181561 (e-PCR)
- UniSTS:155287

RH70248 (e-PCR)
- UniSTS:43453

RH71032 (e-PCR)
- UniSTS:58320

PMC136957P1 (e-PCR)
- UniSTS:270809

WI-18738 (e-PCR)
- UniSTS:1017

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP-dependent protein binding	IEA Inferred from Electronic Annotation more info
enables amyloid-beta binding	IDA Inferred from Direct Assay more info	PubMed
enables amyloid-beta binding	IPI Inferred from Physical Interaction more info	PubMed
enables amyloid-beta binding	ISS Inferred from Sequence or Structural Similarity more info
enables amyloid-beta binding	TAS Traceable Author Statement more info	PubMed
enables aspartic-type endopeptidase inhibitor activity	ISS Inferred from Sequence or Structural Similarity more info
enables copper ion binding	IDA Inferred from Direct Assay more info	PubMed
enables copper ion binding	TAS Traceable Author Statement more info	PubMed
enables cupric ion binding	IEA Inferred from Electronic Annotation more info
enables cuprous ion binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables glycosaminoglycan binding	ISS Inferred from Sequence or Structural Similarity more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables lamin binding	IEA Inferred from Electronic Annotation more info
enables microtubule binding	IDA Inferred from Direct Assay more info	PubMed
enables molecular adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables molecular condensate scaffold activity	IDA Inferred from Direct Assay more info	PubMed
enables molecular function activator activity	IEA Inferred from Electronic Annotation more info
enables protease binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein-folding chaperone binding	IEA Inferred from Electronic Annotation more info
enables signaling receptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables transmembrane transporter binding	IEA Inferred from Electronic Annotation more info
enables tubulin binding	IDA Inferred from Direct Assay more info	PubMed
enables type 5 metabotropic glutamate receptor binding	ISS Inferred from Sequence or Structural Similarity more info
NOT enables type 8 metabotropic glutamate receptor binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in activation of protein kinase activity	IEA Inferred from Electronic Annotation more info
involved_in cellular response to amyloid-beta	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within cellular response to copper ion	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in dendritic spine maintenance	TAS Traceable Author Statement more info	PubMed
involved_in intracellular copper ion homeostasis	NAS Non-traceable Author Statement more info	PubMed
involved_in learning or memory	ISS Inferred from Sequence or Structural Similarity more info
involved_in long-term memory	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of DNA-binding transcription factor activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of T cell receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of activated T cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of amyloid precursor protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of amyloid-beta formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of calcineurin-NFAT signaling cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of catalytic activity	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of dendritic spine maintenance	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of interleukin-17 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of interleukin-2 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of long-term synaptic potentiation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of protein processing	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of type II interferon production	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron projection maintenance	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of calcium-mediated signaling	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of glutamate receptor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein localization to plasma membrane	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein targeting to membrane	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein destabilization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein homooligomerization	IEA Inferred from Electronic Annotation more info
involved_in regulation of calcium ion import across plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of cell cycle	IEA Inferred from Electronic Annotation more info
involved_in regulation of glutamate receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of peptidyl-tyrosine phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of potassium ion transmembrane transport	IEA Inferred from Electronic Annotation more info
involved_in response to amyloid-beta	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to cadmium ion	IEA Inferred from Electronic Annotation more info
involved_in response to oxidative stress	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	ISS Inferred from Sequence or Structural Similarity more info
located_in cell surface	HDA more info	PubMed
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in dendrite	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
located_in external side of plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extrinsic component of membrane	TAS Traceable Author Statement more info	PubMed
located_in inclusion body	IMP Inferred from Mutant Phenotype more info	PubMed
located_in intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info
located_in membrane raft	IDA Inferred from Direct Assay more info	PubMed
located_in membrane raft	IMP Inferred from Mutant Phenotype more info	PubMed
located_in membrane raft	ISS Inferred from Sequence or Structural Similarity more info
located_in mitochondrial outer membrane	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear membrane	IDA Inferred from Direct Assay more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in postsynapse	TAS Traceable Author Statement more info	PubMed
located_in postsynaptic density	ISS Inferred from Sequence or Structural Similarity more info
located_in postsynaptic density	TAS Traceable Author Statement more info	PubMed
located_in terminal bouton	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: major prion protein; alternative prion protein

Names: CD230 antigen; prion-related protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009087.1 RefSeqGene

Range

5306..20438

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000311.5 → NP_000302.1 major prion protein preproprotein Prp precursor

See identical proteins and their annotated locations for NP_000302.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript. Variants 1-5 can all encode the same isoform (Prp).

Source sequence(s)

AI131269, DC325819, M13899

Consensus CDS

CCDS13080.1

UniProtKB/Swiss-Prot

O60489, P04156, P78446, Q15216, Q15221, Q27H91, Q5QPB4, Q8TBG0, Q96E70, Q9UP19

UniProtKB/TrEMBL

A0A6J4EE43, B2R5Q9, Q53YK7, Q6FGN5

Related

ENSP00000368752.4, ENST00000379440.9

Conserved Domains (3) summary

smart00157
Location:23 → 240

PRP; Major prion protein

pfam00377
Location:134 → 251

Prion; Prion/Doppel alpha-helical domain

pfam11587
Location:1 → 28

Prion_bPrPp; Major prion protein bPrPp - N terminal
NM_001080121.3 → NP_001073590.1 major prion protein preproprotein Prp precursor

See identical proteins and their annotated locations for NP_001073590.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1-5 can all encode the same protein (Prp).

Source sequence(s)

AI131269, BP251427, M13899

Consensus CDS

CCDS13080.1

UniProtKB/Swiss-Prot

O60489, P04156, P78446, Q15216, Q15221, Q27H91, Q5QPB4, Q8TBG0, Q96E70, Q9UP19

UniProtKB/TrEMBL

A0A6J4EE43, B2R5Q9, Q53YK7, Q6FGN5

Related

ENSP00000411599.2, ENST00000424424.2

Conserved Domains (3) summary

smart00157
Location:23 → 240

PRP; Major prion protein

pfam00377
Location:134 → 251

Prion; Prion/Doppel alpha-helical domain

pfam11587
Location:1 → 28

Prion_bPrPp; Major prion protein bPrPp - N terminal
NM_001080122.3 → NP_001073591.1 major prion protein preproprotein Prp precursor

See identical proteins and their annotated locations for NP_001073591.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Variants 1-5 can all encode the same protein (Prp).

Source sequence(s)

AI131269, BI669189, M13899

Consensus CDS

CCDS13080.1

UniProtKB/Swiss-Prot

O60489, P04156, P78446, Q15216, Q15221, Q27H91, Q5QPB4, Q8TBG0, Q96E70, Q9UP19

UniProtKB/TrEMBL

A0A6J4EE43, B2R5Q9, Q53YK7, Q6FGN5

Conserved Domains (3) summary

smart00157
Location:23 → 240

PRP; Major prion protein

pfam00377
Location:134 → 251

Prion; Prion/Doppel alpha-helical domain

pfam11587
Location:1 → 28

Prion_bPrPp; Major prion protein bPrPp - N terminal
NM_001080123.3 → NP_001073592.1 major prion protein preproprotein Prp precursor

See identical proteins and their annotated locations for NP_001073592.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR compared to variant 1. Variants 1-5 can all encode the same protein (Prp).

Source sequence(s)

AI131269, AL133396, DB461478, DB485147, M13899

Consensus CDS

CCDS13080.1

UniProtKB/Swiss-Prot

O60489, P04156, P78446, Q15216, Q15221, Q27H91, Q5QPB4, Q8TBG0, Q96E70, Q9UP19

UniProtKB/TrEMBL

A0A6J4EE43, B2R5Q9, Q53YK7, Q6FGN5

Related

ENSP00000415284.2, ENST00000457586.2

Conserved Domains (3) summary

smart00157
Location:23 → 240

PRP; Major prion protein

pfam00377
Location:134 → 251

Prion; Prion/Doppel alpha-helical domain

pfam11587
Location:1 → 28

Prion_bPrPp; Major prion protein bPrPp - N terminal
NM_001271561.3 → NP_001258490.1 alternative prion protein isoform AltPrp

See identical proteins and their annotated locations for NP_001258490.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) encodes multiple distinct proteins due to the use of alternate translation initiation codons. The longer protein (Prp, PMID:21478263) represents the canonical protein, while a shorter protein (AltPrp, PMID:21478263) that uses a different, but overlapping reading frame has also been described. Alternative prion protein (AltPrp) has no sequence similarity to Prp and localizes to the outer mitochondrial membrane. This RefSeq represents the shorter protein, AltPrp.

Source sequence(s)

AI131269, AY008282, BC022532, DC325819

UniProtKB/Swiss-Prot

F7VJQ1

UniProtKB/TrEMBL

K0P2W7
NM_183079.4 → NP_898902.1 major prion protein preproprotein Prp precursor

See identical proteins and their annotated locations for NP_898902.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. This variant (2) encodes multiple distinct proteins due to the use of alternate translation initiation codons. The longer protein (Prp, PMID:21478263) represents the canonical protein, while a shorter protein (AltPrp, PMID:21478263) that uses a different, but overlapping reading frame has also been described. This RefSeq represents the longer protein, Prp. Variants 1-5 can all encode the same protein (Prp).

Source sequence(s)

AI131269, AY008282, BC022532, DC325819

Consensus CDS

CCDS13080.1

UniProtKB/Swiss-Prot

O60489, P04156, P78446, Q15216, Q15221, Q27H91, Q5QPB4, Q8TBG0, Q96E70, Q9UP19

UniProtKB/TrEMBL

A0A6J4EE43, B2R5Q9, Q53YK7, Q6FGN5

Related

ENSP00000399376.2, ENST00000430350.2

Conserved Domains (3) summary

smart00157
Location:23 → 240

PRP; Major prion protein

pfam00377
Location:134 → 251

Prion; Prion/Doppel alpha-helical domain

pfam11587
Location:1 → 28

Prion_bPrPp; Major prion protein bPrPp - N terminal