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UniProtKB/Swiss-Prot P16473: Variant p.Ser505Asn

Thyrotropin receptor
Gene: TSHR
Variant information

Variant position:  505
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 505 (S505N, p.Ser505Asn).
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; found in toxic thyroid nodules.
Any additional useful information about the variant.



Sequence information

Variant position:  505
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:   AIDWQTGPGCNTAGFFTVFA  S ELSVYTLTVITLERWYAITF
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                         AIDWQTGPGCNTAGFFTVFASELSVYTLTVITLERWYAITF

                              AIDWQTGPGCNTAGFFTVFASELSVYTLTVITLERWYAITF

Mouse                         AIDWQTGPGCNTAGFFTVFASELSVYTLTVITLERWYAITF

Rat                           AIDWQTGPGCNTAGFFTVFASELSVYTLTVITLERWYAITF

Pig                           AIDWQTGPGCNTAGFFTVFASELSVYTLTVITLERWYAITF

Bovine                        AIDWQTGPGCNTAGFFTVFASELSVYTLTVITLERWHAITF

Sheep                         AIDWQTGPGCNTAGFFTVFASELSVYTLTVITLERWYAITF

Cat                           AIDWQTGPGCNAAGFFTVFASELSVYTLTVITLERWYAITF

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 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.


Literature citations

Sporadic congenital hyperthyroidism due to a spontaneous germline mutation in the thyrotropin receptor gene.
Holzapfel H.P.; Wonerow P.; von Petrykowski W.; Henschen M.; Scherbaum W.A.; Paschke R.;
J. Clin. Endocrinol. Metab. 82:3879-3884(1997)
Cited for: VARIANT HTNA ASN-505;

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;

Premature birth and low birth weight associated with nonautoimmune hyperthyroidism due to an activating thyrotropin receptor gene mutation.
Vaidya B.; Campbell V.; Tripp J.H.; Spyer G.; Hattersley A.T.; Ellard S.;
Clin. Endocrinol. (Oxf.) 60:711-718(2004)
Cited for: VARIANT HTNA ASN-505;

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.