Home  |  Contact

UniProtKB/Swiss-Prot P16473: Variant p.Ser281Asn

Thyrotropin receptor
Gene: TSHR
Variant information

Variant position:  281
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 Serine (S) to Asparagine (N) at position 281 (S281N, p.Ser281Asn).
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 polar (S) to medium size and polar (N)
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; gain of function; found in toxic thyroid nodules and hyperfunctioning thyroid adenomas.
Any additional useful information about the variant.



Sequence information

Variant position:  281
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:   KKLPLSLSFLHLTRADLSYP  S HCCAFKNQKKIRGILESLMC
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                         KKLPLSLSFLHLTRADLSYPSHCCAFKNQKKIRGILESLMC

                              KKLPLSLSFLHLTRADLSYPSHCCAFKNQKKIRGILESLMC

Mouse                         KKLPLSLSFLHLTRADLSYPSHCCAFKNQKKIRGILESLMC

Rat                           KKLPLSLSFLHLTRADLSYPSHCCAFKNQKKIRGILESLMC

Pig                           KKLPLSLSFLHLTRADLSYPSHCCAFKNQKKIRGILESLMC

Bovine                        RKLPLSLSFLHLTRADLSYPSHCCAFKNQKKIRGILQSLMC

Sheep                         KKLPLSLSFLHLTRADLSYPSHCCAFKNQKNIRGILQSLMC

Cat                           KKLPLTLSFLHLTRADLSYPSHCCAFKNQKKIRGILESFMC

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
Topological domain 21 – 413 Extracellular
Alternative sequence 254 – 764 Missing. In isoform Short.
Alternative sequence 275 – 764 Missing. In isoform 3.
Mutagenesis 283 – 283 C -> S. Abolishes cell surface expression.


Literature citations

Diversity and prevalence of somatic mutations in the thyrotropin receptor and Gs alpha genes as a cause of toxic thyroid adenomas.
Parma J.; Duprez L.; van Sande J.; Hermans J.; Rocmans P.; van Vliet G.; Costagliola S.; Rodien P.; Dumont J.E.; Vassart G.;
J. Clin. Endocrinol. Metab. 82:2695-2701(1997)
Cited for: VARIANTS HYPERTHYROIDISM ASN-281; THR-281; THR-453; PHE-486; MET-486; THR-568; GLY-619; ILE-623; PHE-629; LEU-630; LEU-631; ILE-632; ALA-633; GLU-633; HIS-633; TYR-633 AND 658-ASN--ILE-661 DEL;

Severe congenital hyperthyroidism caused by a germ-line neo mutation in the extracellular portion of the thyrotropin receptor.
Grueters A.; Schoeneberg T.; Biebermann H.; Krude H.; Krohn H.P.; Dralle H.; Gudermann T.;
J. Clin. Endocrinol. Metab. 83:1431-1436(1998)
Cited for: VARIANT HTNA ASN-281; VARIANT HIS-528;

Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter.
Tonacchera M.; Agretti P.; Chiovato L.; Rosellini V.; Ceccarini G.; Perri A.; Viacava P.; Naccarato A.G.; Miccoli P.; Pinchera A.; Vitti P.;
J. Clin. Endocrinol. Metab. 85:2270-2274(2000)
Cited for: VARIANTS HTNA ASN-281; MET-486; PHE-486; PHE-629; ALA-632; ILE-632; GLU-633 AND VAL-647;

Constitutively activating TSH-receptor mutations as a molecular cause of non-autoimmune hyperthyroidism in childhood.
Biebermann H.; Schoeneberg T.; Krude H.; Gudermann T.; Grueters A.;
Langenbecks Arch. Surg. 385:390-392(2000)
Cited for: VARIANTS HTNA ASN-281; SER-431 AND ILE-632;

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;

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.