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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P16473: Variant p.Leu512Arg

Thyrotropin receptor
Gene: TSHR
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Variant information Variant position: help 512 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help US 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: help From Leucine (L) to Arginine (R) at position 512 (L512R, p.Leu512Arg). 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: help Change from medium size and hydrophobic (L) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -2 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: help In hyperthyroidism; found in autonomously functioning thyroid nodules; 3.3-fold increase in basal cAMP level. Any additional useful information about the variant.


Sequence information Variant position: help 512 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 764 The length of the canonical sequence.
Location on the sequence: help PGCNTAGFFTVFASELSVYT L TVITLERWYAITFAMRLDRK 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         PGCNTAGFFTVFASELSVYTLTVITLERWYAITFAMRLDRK

                              PGCNTAGFFTVFASELSVYTLTVITLERWYAITFAMRLDRK

Mouse                         PGCNTAGFFTVFASELSVYTLTVITLERWYAITFAMRLDRK

Rat                           PGCNTAGFFTVFASELSVYTLTVITLERWYAITFAMRLDRK

Pig                           PGCNTAGFFTVFASELSVYTLTVITLERWYAITFAMRLDRK

Bovine                        PGCNTAGFFTVFASELSVYTLTVITLERWHAITFAMRLDRK

Sheep                         PGCNTAGFFTVFASELSVYTLTVITLERWYAITFAMHLDRK

Cat                           PGCNAAGFFTVFASELSVYTLTVITLERWYAITFAMRLDRK

Sequence annotation in neighborhood: help 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 495 – 517 Helical; Name=3
Disulfide bond 494 – 569
Alternative sequence 254 – 764 Missing. In isoform Short.
Alternative sequence 275 – 764 Missing. In isoform 3.
Helix 492 – 524



Literature citations
A novel activating mutation in the thyrotropin receptor gene in an autonomously functioning thyroid nodule developed by a Japanese patient.
Kosugi S.; Hai N.; Okamoto H.; Sugawa H.; Mori T.;
Eur. J. Endocrinol. 143:471-477(2000)
Cited for: VARIANT HYPERTHYROIDISM ARG-512; CHARACTERIZATION OF VARIANT HYPERTHYROIDISM ARG-512; Detection of thyroid-stimulating hormone receptor and G(s)alpha mutations: in 75 toxic thyroid nodules by denaturing gradient gel electrophoresis.
Truelzsch B.; Krohn K.; Wonerow P.; Chey S.; Holzapfel H.-P.; Ackermann F.; Fuehrer D.; Paschke R.;
J. Mol. Med. 78:684-691(2001)
Cited for: VARIANTS ASN-281; ILE-425; THR-453; PHE-486; ASN-505; ARG-512; GLN-512; THR-568; GLY-619; VAL-623; LEU-631; ALA-632; ILE-632; GLU-633; HIS-633; TYR-633; ALA-639 AND PHE-656; CHARACTERIZATION OF VARIANTS ILE-425 AND GLN-512; Oncogenic mutations in the thyrotropin receptor of autonomously functioning thyroid nodules in the Japanese population.
Vanvooren V.; Uchino S.; Duprez L.; Costa M.J.; Vandekerckhove J.; Parma J.; Vassart G.; Dumont J.E.; van Sande J.; Noguchi S.;
Eur. J. Endocrinol. 147:287-291(2002)
Cited for: VARIANTS HYPERTHYROIDISM THR-453; MET-486; ARG-512 AND ALA-632;
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.