PRNP
protein-codingprion protein, the group of CD molecules
Gene 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]
- PRIP
- GSS
- CJD
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0007656
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0011299
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0007403
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0017233
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0007403
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0018339
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0007403
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0010808
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0007656
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0011299
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0007656
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PRNP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_000311.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 38 | 4 | 44 | ||
| missense | 11 | 12 | 67 | 7 | 2 | 99 |
| nonsense | 4 | 1 | 2 | 7 | ||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 15 | 13 | 72 | 45 | 6 | 151 |
Highest pathogenic variant AF is 0.0000867408
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_000302.1 | 1 | MANE Select | |
| Ensembl | ENSP00000368752.4 | 1 | MANE Select | |
| RefSeq | NP_001073590.1 | 1 | Standard | |
| RefSeq | NP_001073591.1 | 1 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Prion diseases - Homo sapiens (human)
- Ferroptosis - Homo sapiens (human)
- Human Complement System
- Copper homeostasis
- Prion disease pathway
Biological Process
- negative regulation of protein phosphorylation
- cellular copper ion homeostasis
- response to oxidative stress
- cell cycle arrest
- learning or memory
Molecular Function
- amyloid-beta binding
- protease binding
- copper ion binding
- protein binding
- lamin binding
Cellular Component
- cytoplasm
- endoplasmic reticulum
- Golgi apparatus
- cytosol
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000379440
- Coding exons
- 1
- Length
- 15355
- Individuals with no LoFs
- 125738
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125746
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.18 | 111 | 152 | 0.731 | 0.00000905 | 1663 |
| Missense (PolyPhen) | 39 | 60.86 | 0.64081 | 655 | ||
| Synonymous | -0.476 | 63 | 58.4 | 1.08 | 0.00000399 | 491 |
| Loss of Function | 0.950 | 6 | 9.09 | 0.660 | 4.86e-7 | 84 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00011 | 0.000054 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.000027 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.664
Intolerance Scores
- LoFtool
- 0.0143
- RVIS EVS
- 0.37
- RVIS percentile EVS
- 75.12
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.982
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |