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UniProtKB/Swiss-Prot P10828: Variant p.Arg316His

Thyroid hormone receptor beta
Gene: THRB
Variant information

Variant position:  316
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 Arginine (R) to Histidine (H) at position 316 (R316H, p.Arg316His).
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 large size and basic (R) to medium size and polar (H)
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:  Selective pituitary thyroid hormone resistance (PRTH) [MIM:145650]: Variant form of thyroid hormone resistance and is characterized by clinical hyperthyroidism, with elevated free thyroid hormones, but inappropriately normal serum TSH. Unlike GRTH, where the syndrome usually segregates with a dominant allele, the mode of inheritance in PRTH has not been established. {ECO:0000269|PubMed:7528740, ECO:0000269|PubMed:8381821}. 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 PRTH; impairs hormone binding.
Any additional useful information about the variant.

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



Sequence information

Variant position:  316
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  461
The length of the canonical sequence.

Location on the sequence:   LPCEDQIILLKGCCMEIMSL  R AAVRYDPESETLTLNGEMAV
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                         LPCEDQIILLKGCCMEIMSLRAAVRYDPESETLTLNGEMAV

Mouse                         LPCEDQIILLKGCCMEIMSLRAAVRYDPDSETLTLNGEMAV

Rat                           LPCEDQIILLKGCCMEIMSLRAAVRYDPDSETLTLNGEMAV

Chicken                       LPCEDQIILLKGCCMEIMSLRAAVRYDPESETLTLNGEMAV

Zebrafish                     LPCEDQIILLKGCCMEIMSLRAAVRYDPESDTLTLNGEMAV

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 – 461 Thyroid hormone receptor beta
Domain 217 – 461 NR LBD
Region 244 – 461 Interaction with NR2F6
Binding site 320 – 320 Thyroid hormone
Binding site 331 – 331 Thyroid hormone; via amide nitrogen
Mutagenesis 331 – 331 N -> S. No effect on thyroid hormone binding.
Helix 298 – 319


Literature citations

Two resistance to thyroid hormone mutants with impaired hormone binding.
Huber B.R.; Sandler B.; West B.L.; Cunha Lima S.T.; Nguyen H.T.; Apriletti J.W.; Baxter J.D.; Fletterick R.J.;
Mol. Endocrinol. 17:643-652(2003)
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 202-461 OF VARIANT PTHR HIS-316 AND VARIANT GTHR THR-317; CHARACTERIZATION OF VARIANT PTHR HIS-316; CHARACTERIZATION OF VARIANT GTHR THR-317;

An arginine to histidine mutation in codon 311 of the C-erbA beta gene results in a mutant thyroid hormone receptor that does not mediate a dominant negative phenotype.
Geffner M.E.; Su F.; Ross N.S.; Hershman J.M.; van Dop C.; Menke J.B.; Hao E.; Stanzak R.K.; Eaton T.; Samuels H.H.; Usala S.J.;
J. Clin. Invest. 91:538-546(1993)
Cited for: VARIANT PRTH HIS-316;

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.