UniProtKB/Swiss-Prot P04156: Variant p.Ala117Val

Major prion protein
Gene: PRNP
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Variant information Variant position:

117 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Alanine (A) to Valine (V) at position 117 (A117V, p.Ala117Val). 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 small size and hydrophobic (A) to medium size and hydrophobic (V) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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
Polymorphism:

The five tandem octapeptide repeats region is highly unstable. Insertions or deletions of octapeptide repeat units are associated to prion disease.A number of polymorphisms confer resistance to prion diseases (PubMed:1439789, PubMed:9482303, PubMed:19923577, PubMed:26061765). Val-127 has been selected for in response to the Kuru epidemic and confers resistance to prion disease by acting as a 'dominant negative' inhibitor of prion conversion (PubMed:26061765). Val-127 is not only itself resistant to conformational conversion, but also inhibits conversion of wild-type proteins. Confers protection against classical Creutzfeldt-Jakob disease (CJD) and Kuru in the heterozygous state, but can be infected with variant CJD prions, resulting from exposure to bovine spongiform encephalopathy prions. Confers complete resistance to all prion strains when homozygous (PubMed:26061765). Always associated with M-129 variant (PubMed:26061765). Val-129 confers relative protection against acquired, sporadic and some inherited prion diseases in the heterozygous state, possibly by preventing homodimerization (PubMed:1439789). Lys-219 confers relative protection against sporadic Creutzfeldt-Jakob disease (CJD) in the heterozygous state (PubMed:9482303). - Additional information on the polymorphism described.
Variant description:

Linked to development of dementing Gerstmann-Straussler disease. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs74315402 [ dbSNP | Ensembl ]

Sequence information Variant position:

117 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:

SQWNKPSKPKTNMKHMAGAA A AGAVVGGLGGYMLGSAMSRP 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                         SQWNKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRP

Gorilla                       SQWNKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRP

                              SQWNKPSKPKTNMKHVAGAAAAGAVVGGLGGYLLGSAMSRP

Rhesus macaque                NQWHKPSKPKTSMKHMAGAAAAGAVVGGLGGYMLGSAMSRP

Chimpanzee                    SQWNKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRP

Mouse                         NQWNKPSKPKTNLKHVAGAAAAGAVVGGLGGYMLGSAMSRP

Rat                           NQWNKPSKPKTNLKHVAGAAAAGAVVGGLGGYMLGSAMSRP

Pig                           GQWNKPSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRP

Bovine                        GQWNKPSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRP

Rabbit                        NQWGKPSKPKTSMKHVAGAAAAGAVVGGLGGYMLGSAMSRP

Goat                          SQWNKPSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRP

Sheep                         SQWNKPSKPKTNMKHVAGAAAAGAVVGGLGGYMLGSAMSRP

Cat                           SQWNKPSKPKTNMKHMAGAAAAGAVVGGLGGYMLGSAMSRP

Chicken                       HNQKPWKPPKTNFKHVAGAAAAGAVVGGLGGYAMGRVMSGM

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.

Type	Positions	Description
Chain	23 – 230	Major prion protein
Region	23 – 230	Interaction with GRB2, ERI3 and SYN1
Turn	114 – 117

Literature citations
Pro-->Leu change at position 102 of prion protein is the most common but not the sole mutation related to Gerstmann-Straussler syndrome.
Doh-Ura K.; Tateishi J.; Sasaki H.; Kitamoto T.; Sakaki Y.;
Biochem. Biophys. Res. Commun. 163:974-979(1989)
Cited for: VARIANTS LEU-102; VAL-117 AND VAL-129;

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.