UniProtKB/Swiss-Prot P04156: Variant p.Glu196Lys

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

Variant position:  196
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 Glutamate (E) to Lysine (K) at position 196 (E196K, p.Glu196Lys).
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:  Change from medium size and acidic (E) to large size and basic (K)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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.



Sequence information

Variant position:  196
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:   VHDCVNITIKQHTVTTTTKG  E NFTETDVKMMERVVEQMCIT
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                         VHDCVNITIKQHTVTTTTK--------GENFTETDV--KMMERVVEQMCIT

Gorilla                       VHDCVNITIKQHTVTTTTK--------GENFTETDV--KMM

                              VHDCVNITVKQHTVTTT-K--------GENFTETDI--KMM

Rhesus macaque                VHDCVNITIKQHTVTTTTK--------GENFTETDV--KMM

Chimpanzee                    VHDCVNITIKQHTVTTTTK--------GENFTETDV--KMM

Mouse                         VHDCVNITIKQHTVTTTTK--------GENFTETDV--KMM

Rat                           VHDCVNITIKQHTVTTTTK--------GENFTETDV--KMM

Pig                           VHDCVNITVKQHTVTTTTK--------GENFTETDV--KMI

Bovine                        VHDCVNITVKEHTVTTTTK--------GENFTETDI--KMM

Rabbit                        VHDCVNITVKQHTVTTTTK--------GENFTETDI--KIM

Goat                          VHDCVNITVKQHTVTTTTK--------GENFTETDI--KIM

Sheep                         VHDCVNITVKQHTVTTTTK--------GENFTETDI--KIM

Cat                           VHDCVNITVKQHTVTTTTK--------GENFTETDM--KIM

Chicken                       VADCFNITVTEYSIGPAAKKNTSEAVAAANQTEVEMENKVV

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


Literature citations

Identification of three novel mutations (E196K, V203I, E211Q) in the prion protein gene (PRNP) in inherited prion diseases with Creutzfeldt-Jakob disease phenotype.
Peoc'h K.; Manivet P.; Beaudry P.; Attane F.; Besson G.; Didier H.; Delasnerie-Laupretre N.; Laplanche J.-L.;
Hum. Mutat. 15:482-482(2000)
Cited for: VARIANTS CJD LYS-196; ILE-203 AND GLN-211;

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.