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UniProtKB/Swiss-Prot P10827: Variant p.Ala263Val

Thyroid hormone receptor alpha
Gene: THRA
Variant information

Variant position:  263
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 Valine (V) at position 263 (A263V, p.Ala263Val).
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

Involvement in disease:  Hypothyroidism, congenital, non-goitrous, 6 (CHNG6) [MIM:614450]: A disease characterized by growth retardation, developmental retardation, skeletal dysplasia, borderline low thyroxine levels and high triiodothyronine levels. There is differential sensitivity to thyroid hormone action, with retention of hormone responsiveness in the hypothalamic pituitary axis and liver but skeletal, gastrointestinal, and myocardial resistance. {ECO:0000269|PubMed:22168587, ECO:0000269|PubMed:24969835, ECO:0000269|PubMed:25670821, ECO:0000269|PubMed:26037512}. 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 CHNG6; no effect on T3 binding; no effect on thyroid hormone-dependent transcriptional activation.
Any additional useful information about the variant.

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



Sequence information

Variant position:  263
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  490
The length of the canonical sequence.

Location on the sequence:   PCEDQIILLKGCCMEIMSLR  A AVRYDPESDTLTLSGEMAVK
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.

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 1 – 490 Thyroid hormone receptor alpha
Domain 163 – 407 NR LBD
Binding site 277 – 277 Thyroid hormone; via amide nitrogen
Mutagenesis 277 – 277 S -> N. No effect on thyroid hormone binding.
Helix 244 – 264


Literature citations

Resistance to thyroid hormone caused by a mutation in thyroid hormone receptor (TR)alpha1 and TRalpha2: clinical, biochemical, and genetic analyses of three related patients.
Moran C.; Agostini M.; Visser W.E.; Schoenmakers E.; Schoenmakers N.; Offiah A.C.; Poole K.; Rajanayagam O.; Lyons G.; Halsall D.; Gurnell M.; Chrysis D.; Efthymiadou A.; Buchanan C.; Aylwin S.; Chatterjee K.K.;
Lancet Diabetes Endocrinol. 2:619-626(2014)
Cited for: VARIANT CHNG6 VAL-263; CHARACTERIZATION OF VARIANT VAL-263 (ISOFORM ALPHA-1); CHARACTERIZATION OF VARIANT VAL-263 (ISOFORM ALPHA-2);

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.