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UniProtKB/Swiss-Prot P02766: Variant p.Ala129Thr

Transthyretin
Gene: TTR
Chromosomal location: 18q12.1
Variant information

Variant position:  129
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 Alanine (A) to Threonine (T) at position 129 (A129T, p.Ala129Thr).
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 polar (T)
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

Involvement in disease:  Hyperthyroxinemia, dystransthyretinemic (DTTRH) [MIM:145680]: A condition characterized by elevation of total and free thyroxine in healthy, euthyroid persons without detectable binding protein abnormalities. {ECO:0000269|PubMed:1979335}. 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 DTTRH; increased affinity for thyroxine.
Any additional useful information about the variant.

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



Sequence information

Variant position:  129
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  147
The length of the canonical sequence.

Location on the sequence:   EHAEVVFTANDSGPRRYTIA  A LLSPYSYSTTAVVTNPKE
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                         EHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE---

Chimpanzee                    EHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTIPKE

Mouse                         EFADVVFTANDSGHRHYTIAALLSPYSYSTTAVVSNPQN

Rat                           EYAEVVFTANDSGHRHYTIAALLSPYSYSTTAVVSNPQN

Pig                           EYAEVVFTANDSGRRHYTIAALLSPYSYSTTALVSSPKE

Bovine                        EFAEVVFTANDSGPRHYTIAALLSPYSYSTTALVSSPKA

Rabbit                        EYAEVVFTANDSGHRSYTIAALLSPFSYSTTAVVSNPQE

Sheep                         EYAEVVFTANDSGLRHYTIAALLSPYSYSTTALVSSPKE

Chicken                       EYADVVFTANDSGHRHYTIAALLSPFSYSTTAVVSDPQE

Xenopus laevis                EYVDVVFTANDAGHRHYTIAVLLTPYSFSSTAIVSEPHD

Xenopus tropicalis            EYVDVVFSANDAGHRHYTIAVLLTPYSISSTAVVSEPHD

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 21 – 147 Transthyretin
Glycosylation 118 – 118 N-linked (GlcNAc...) asparagine
Mutagenesis 130 – 130 L -> M. Loss of tetramerization; when associated with M-107.
Beta strand 124 – 132


Literature citations

A point mutation in transthyretin increases affinity for thyroxine and produces euthyroid hyperthyroxinemia.
Moses A.C.; Rosen H.N.; Moller D.E.; Tsuzaki S.; Haddow J.E.; Lawlor J.; Liepnieks J.J.; Nichols W.C.; Benson M.D.;
J. Clin. Invest. 86:2025-2033(1990)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 113-129; VARIANT DTTRH THR-129;

Genetic microheterogeneity of human transthyretin detected by IEF.
Altland K.; Benson M.D.; Costello C.E.; Ferlini A.; Hazenberg B.P.C.; Hund E.; Kristen A.V.; Linke R.P.; Merlini G.; Salvi F.; Saraiva M.J.; Singer R.; Skinner M.; Winter P.;
Electrophoresis 28:2053-2064(2007)
Cited for: VARIANTS AMYL-TTR PRO-32; ILE-40; SER-44; ALA-50; MET-50; LEU-53; VAL-53; PRO-56; THR-65; ALA-67; ALA-69; ILE-69; ALA-80; LEU-84; LEU-88; ALA-91; TYR-97; PHE-98; SER-104; ASN-104; THR-104; ALA-114; GLY-117; ASN-126; MET-127; VAL-127; MET-131 AND ILE-142; VARIANTS ILE-33; SER-121 AND THR-129; VARIANT CHICAGO MET-139;

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.