UniProtKB/Swiss-Prot P04156: Variant p.Gly127Val

Major prion protein
Gene: PRNP
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Variant information Variant position:

127 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 Glycine (G) to Valine (V) at position 127 (G127V, p.Gly127Val). 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 glycine (G) to medium size and hydrophobic (V) 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
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:

Protective factor against Kuru; protective factor against prion disease; 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; acts as a 'dominant negative' inhibitor of prion conversion; is not only itself resistant to conformational conversion, but also inhibits conversion of wild-type proteins. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs267606980 [ dbSNP | Ensembl ]

Sequence information Variant position:

127 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:

TNMKHMAGAAAAGAVVGGLG G YMLGSAMSRPIIHFGSDYED 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                         TNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPIIHFGSDYED

Gorilla                       TNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPIIHFGSDYED

                              TNMKHVAGAAAAGAVVGGLGGYLLGSAMSRPLIHFGNDCED

Rhesus macaque                TSMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYED

Chimpanzee                    TNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPIIHFGSDYED

Mouse                         TNLKHVAGAAAAGAVVGGLGGYMLGSAMSRPMIHFGNDWED

Rat                           TNLKHVAGAAAAGAVVGGLGGYMLGSAMSRPMLHFGNDWED

Pig                           TNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGSDYED

Bovine                        TNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGSDYED

Rabbit                        TSMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYED

Goat                          TNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYED

Sheep                         TNMKHVAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYED

Cat                           TNMKHMAGAAAAGAVVGGLGGYMLGSAMSRPLIHFGNDYED

Chicken                       TNFKHVAGAAAAGAVVGGLGGYAMGRVMSGMNYHFDSPDEY

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
Beta strand	125 – 127

Literature citations
A novel protective prion protein variant that colocalizes with kuru exposure.
Mead S.; Whitfield J.; Poulter M.; Shah P.; Uphill J.; Campbell T.; Al-Dujaily H.; Hummerich H.; Beck J.; Mein C.A.; Verzilli C.; Whittaker J.; Alpers M.P.; Collinge J.;
N. Engl. J. Med. 361:2056-2065(2009)
Cited for: VARIANT VAL-127; INVOLVEMENT IN KURU; A naturally occurring variant of the human prion protein completely prevents prion disease.
Asante E.A.; Smidak M.; Grimshaw A.; Houghton R.; Tomlinson A.; Jeelani A.; Jakubcova T.; Hamdan S.; Richard-Londt A.; Linehan J.M.; Brandner S.; Alpers M.; Whitfield J.; Mead S.; Wadsworth J.D.; Collinge J.;
Nature 522:478-481(2015)
Cited for: VARIANT VAL-127; CHARACTERIZATION OF VARIANT VAL-127; INVOLVEMENT IN KURU; POLYMORPHISM;

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.