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UniProtKB/Swiss-Prot P04156: Variant p.Thr183Ala

Major prion protein
Gene: PRNP
Variant information

Variant position:  183
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
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 Threonine (T) to Alanine (A) at position 183 (T183A, p.Thr183Ala).
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 polar (T) to small size and hydrophobic (A)
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

Variant description:  In SENF and early-onset dementia; induces loss of glycosylation at N-181.
Any additional useful information about the variant.

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



Sequence information

Variant position:  183
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:   YRPMDEYSNQNNFVHDCVNI  T IKQHTVTTTTKGENFTETDV
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                         YRPMDEYSNQNNFVHDCVNITIKQHTVTTTTK--------GENFTETDV--

Gorilla                       YRPMDQYSNQNNFVHDCVNITIKQHTVTTTTK--------G

                              YRSVDQYNNQSTFVHDCVNITVKQHTVTTT-K--------G

Rhesus macaque                YRPVDQYSNQNNFVHDCVNITIKQHTVTTTTK--------G

Chimpanzee                    YRPMDQYSSQNNFVHDCVNITIKQHTVTTTTK--------G

Mouse                         YRPVDQYSNQNNFVHDCVNITIKQHTVTTTTK--------G

Rat                           YRPVDQYSNQNNFVHDCVNITIKQHTVTTTTK--------G

Pig                           YRPVDQYSNQNSFVHDCVNITVKQHTVTTTTK--------G

Bovine                        YRPVDQYSNQNNFVHDCVNITVKEHTVTTTTK--------G

Rabbit                        YRPVDQYSNQNSFVHDCVNITVKQHTVTTTTK--------G

Goat                          YRPVDQYSNQNNFVHDCVNITVKQHTVTTTTK--------G

Sheep                         YRPVDRYSNQNNFVHDCVNITVKQHTVTTTTK--------G

Cat                           YRPVDQYSNQNNFVHDCVNITVKQHTVTTTTK--------G

Chicken                       YRDYSSPVPQDVFVADCFNITVTEYSIGPAAKKNTSEAVAA

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...) asparagine
Glycosylation 197 – 197 N-linked (GlcNAc...) asparagine
Disulfide bond 179 – 214
Beta strand 182 – 185


Literature citations

The Thr183Ala mutation, not the loss of the first glycosylation site, alters the physical properties of the prion protein.
Capellari S.; Zaidi S.I.; Long A.C.; Kwon E.E.; Petersen R.B.;
J. Alzheimers Dis. 2:27-35(2000)
Cited for: GLYCOSYLATION AT ASN-181; VARIANT SENF ALA-183; CHARACTERIZATION OF VARIANT SENF ALA-183;

Familial spongiform encephalopathy associated with a novel prion protein gene mutation.
Nitrini R.; Rosemberg S.; Passos-Bueno M.R.; da Silva L.S.; Iughetti P.; Papadopoulos M.; Carrilho P.M.; Caramelli P.; Albrecht S.; Zatz M.; Leblanc A.;
Ann. Neurol. 42:138-146(1997)
Cited for: VARIANT SENF ALA-183;

High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes.
Finckh U.; Mueller-Thomsen T.; Mann U.; Eggers C.; Marksteiner J.; Meins W.; Binetti G.; Alberici A.; Hock C.; Nitsch R.M.; Gal A.;
Am. J. Hum. Genet. 66:110-117(2000)
Cited for: VARIANTS EARLY-ONSET DEMENTIA LEU-102; ALA-183 AND LYS-188;

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.