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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P16473: Variant p.Cys390Trp

Thyrotropin receptor
Gene: TSHR
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Variant information Variant position: help 390 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] 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 Cysteine (C) to Tryptophan (W) at position 390 (C390W, p.Cys390Trp). 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 polar (C) to large size and aromatic (W) 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 CHNG1; persistent hypothyroidism and defective thyroid development; abolishes high affinity hormone binding. Any additional useful information about the variant.


Sequence information Variant position: help 390 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 LKNPQEETLQAFDSHYDYTI C GDSEDMVCTPKSDEFNPCED 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                         LKNPQEETLQAFDSHYDYTICGDSEDMVCTPKSDEFNPCED

                              LKNPQEETLQAFDSHYDYTVCGGNEDMVCTPKSDEFNPCED

Mouse                         LKNPQEETLQAFESHYDYTVCGDNEDMVCTPKSDEFNPCED

Rat                           LKNPQEETLQAFDSHYDYTVCGDNEDMVCTPKSDEFNPCED

Pig                           LKNPQEETLQAFDSHYDYTVCGGSEDMVCTPKSDEFNPCED

Bovine                        LKNPQEETLQAFDSHYDYTVCGGSEDMVCTPKSDEFNPCED

Sheep                         LKNPQEETLQAFDNHYDYTVCGGSEEMVCTPKSDEFNPCED

Cat                           LKNPQEETLQAFDSHYDYTVCGGNEDMVCTPKSDEFNPCED
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
Topological domain 21 – 413 Extracellular
Modified residue 385 – 385 Sulfotyrosine
Alternative sequence 254 – 764 Missing. In isoform Short.
Alternative sequence 275 – 764 Missing. In isoform 3.
Mutagenesis 385 – 385 Y -> E. Reduces binding with thyrotropin. Inhibits intracellular cAMP accumulation.
Mutagenesis 385 – 385 Y -> F. Reduces sulfation. Reduces binding with thyrotropin. Inhibits intracellular cAMP accumulation.
Mutagenesis 387 – 387 Y -> E. No change in intracellular cAMP accumulation.
Mutagenesis 387 – 387 Y -> F. Reduces sulfation. No change in intracellular cAMP accumulation.



Literature citations
Four families with loss of function mutations of the thyrotropin receptor.
de Roux N.; Misrahi M.; Brauner R.; Houang M.; Carel J.-C.; Granier M.; Le Bouc Y.; Ghinea N.; Boumedienne A.; Toublanc J.E.; Milgrom E.;
J. Clin. Endocrinol. Metab. 81:4229-4235(1996)
Cited for: VARIANTS CHNG1 SER-41; ALA-162; TRP-390; ASN-410 AND LEU-525; Mutations of the human thyrotropin receptor gene causing thyroid hypoplasia and persistent congenital hypothyroidism.
Biebermann H.; Schoeneberg T.; Krude H.; Schultz G.; Gudermann T.; Grueters A.;
J. Clin. Endocrinol. Metab. 82:3471-3480(1997)
Cited for: VARIANT CHNG1 TRP-390;
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.