UniProtKB/Swiss-Prot P04156: Variant p.Val180Ile

Major prion protein
Gene: PRNP
Chromosomal location: 20p13
Variant information

Variant position:  180
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Valine (V) to Isoleucine (I) at position 180 (V180I, p.Val180Ile).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  3
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Creutzfeldt-Jakob disease (CJD) [MIM:123400]: Occurs primarily as a sporadic disorder (1 per million), while 10-15% are familial. Accidental transmission of CJD to humans appears to be iatrogenic (contaminated human growth hormone (HGH), corneal transplantation, electroencephalographic electrode implantation, etc.). Epidemiologic studies have failed to implicate the ingestion of infected animal meat in the pathogenesis of CJD in human. The triad of microscopic features that characterize the prion diseases consists of (1) spongiform degeneration of neurons, (2) severe astrocytic gliosis that often appears to be out of proportion to the degree of nerve cell loss, and (3) amyloid plaque formation. CJD is characterized by progressive dementia and myoclonic seizures, affecting adults in mid-life. Some patients present sleep disorders, abnormalities of high cortical function, cerebellar and corticospinal disturbances. The disease ends in death after a 3-12 months illness. {ECO:0000269|PubMed:10790216, ECO:0000269|PubMed:1439789, ECO:0000269|PubMed:1671440, ECO:0000269|PubMed:1975028, ECO:0000269|PubMed:19927125, ECO:0000269|PubMed:7902693, ECO:0000269|PubMed:7906019, ECO:0000269|PubMed:7913755, ECO:0000269|PubMed:8461023, ECO:0000269|PubMed:8909447}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In CJD.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  180
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  253
The length of the canonical sequence.

Location on the sequence:   QVYYRPMDEYSNQNNFVHDC  V NITIKQHTVTTTTKGENFTE
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         QVYYRPMDEYSNQNNFVHDCVNITIKQHTVTTTTK--------GENFTE

Gorilla                       QVYYRPMDQYSNQNNFVHDCVNITIKQHTVTTTTK------

                              QVYYRSVDQYNNQSTFVHDCVNITVKQHTVTTT-K------

Rhesus macaque                QVYYRPVDQYSNQNNFVHDCVNITIKQHTVTTTTK------

Chimpanzee                    QVYYRPMDQYSSQNNFVHDCVNITIKQHTVTTTTK------

Mouse                         QVYYRPVDQYSNQNNFVHDCVNITIKQHTVTTTTK------

Rat                           QVYYRPVDQYSNQNNFVHDCVNITIKQHTVTTTTK------

Pig                           QVYYRPVDQYSNQNSFVHDCVNITVKQHTVTTTTK------

Bovine                        QVYYRPVDQYSNQNNFVHDCVNITVKEHTVTTTTK------

Rabbit                        QVYYRPVDQYSNQNSFVHDCVNITVKQHTVTTTTK------

Goat                          QVYYRPVDQYSNQNNFVHDCVNITVKQHTVTTTTK------

Sheep                         QVYYRPVDRYSNQNNFVHDCVNITVKQHTVTTTTK------

Cat                           QVYYRPVDQYSNQNNFVHDCVNITVKQHTVTTTTK------

Chicken                       RVYYRDYSSPVPQDVFVADCFNITVTEYSIGPAAKKNTSEA

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 23 – 230 Major prion protein
Region 23 – 230 Interaction with GRB2, ERI3 and SYN1
Glycosylation 181 – 181 N-linked (GlcNAc...)
Glycosylation 197 – 197 N-linked (GlcNAc...)
Disulfide bond 179 – 214
Beta strand 178 – 181


Literature citations

Novel missense variants of prion protein in Creutzfeldt-Jakob disease or Gerstmann-Straussler syndrome.
Kitamoto T.; Ohta M.; Doh-Ura K.; Hitoshi S.; Terao Y.; Tateishi J.;
Biochem. Biophys. Res. Commun. 191:709-714(1993)
Cited for: VARIANTS CJD ILE-180 AND ARG-232;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.