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UniProtKB/Swiss-Prot P16473: Variant p.Val597Phe

Thyrotropin receptor
Gene: TSHR
Variant information

Variant position:  597
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 Valine (V) to Phenylalanine (F) at position 597 (V597F, p.Val597Phe).
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 hydrophobic (V) to large size and aromatic (F)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
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:  Hyperthyroidism, non-autoimmune (HTNA) [MIM:609152]: A condition characterized by abnormally high levels of serum thyroid hormones, thyroid hyperplasia, goiter and lack of anti-thyroid antibodies. Typical features of Graves disease such as exophthalmia, myxedema, antibodies anti-TSH receptor and lymphocytic infiltration of the thyroid gland are absent. {ECO:0000269|PubMed:10199795, ECO:0000269|PubMed:10852462, ECO:0000269|PubMed:11081252, ECO:0000269|PubMed:11127522, ECO:0000269|PubMed:11201847, ECO:0000269|PubMed:11517004, ECO:0000269|PubMed:11549687, ECO:0000269|PubMed:15163335, ECO:0000269|PubMed:7800007, ECO:0000269|PubMed:7920658, ECO:0000269|PubMed:8636266, ECO:0000269|PubMed:8964822, ECO:0000269|PubMed:9349581, ECO:0000269|PubMed:9360555, ECO:0000269|PubMed:9398746, ECO:0000269|PubMed:9589634}. 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 HTNA; 11-fold increase in specific constitutive activity associated with reduction in receptor protein expression.
Any additional useful information about the variant.



Sequence information

Variant position:  597
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  764
The length of the canonical sequence.

Location on the sequence:   PLALAYIVFVLTLNIVAFVI  V CCCYVKIYITVRNPQYNPGD
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                         PLALAYIVFVLTLNIVAFVIVCCCYVKIYITVRNPQYNPGD

                              PLALAYIILVLLLNIVAFIIVCSCYVKIYITVRNPQYNPGD

Mouse                         PLALAYIVLVLLLNVVAFVVVCSCYVKIYITVRNPQYNPRD

Rat                           PLALAYIALVLLLNVVAFVIVCSCYVKIYITVRNPQYNPRD

Pig                           PLALAYIILVLLLNIVAFTIVCSCYVKIYITVRNPQYNPGD

Bovine                        PLALAYIILVLLLNIIAFIIVCACYVKIYITVRNPHYNPGD

Sheep                         PLALAYIILVLLLNIIAFIIVCACYVKIYITVRNPHYNPGD

Cat                           PLALAYIILVLLLNIVAFIIVCSCYVKIYITVRNPQYNTGD

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 – 764 Thyrotropin receptor
Transmembrane 581 – 602 Helical; Name=5
Alternative sequence 254 – 764 Missing. In isoform Short.
Alternative sequence 275 – 764 Missing. In isoform 3.


Literature citations

A novel germline mutation in the TSH receptor gene causes non-autoimmune autosomal dominant hyperthyroidism.
Alberti L.; Proverbio M.C.; Costagliola S.; Weber G.; Beck-Peccoz P.; Chiumello G.; Persani L.;
Eur. J. Endocrinol. 145:249-254(2001)
Cited for: VARIANT HTNA PHE-597; CHARACTERIZATION OF VARIANT HTNA PHE-597;

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.