UniProtKB/Swiss-Prot P16473: Variant p.Pro52Thr

Thyrotropin receptor
Gene: TSHR
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Variant information Variant position:

52 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B 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:

From Proline (P) to Threonine (T) at position 52 (P52T, p.Pro52Thr). 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 (P) to medium size and polar (T) 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
Polymorphism:

The Asp727Glu polymorphism is associated with Graves disease in a Russian population. The Glu727 allele and the heterozygous Asp727Glu genotype are related to higher risk of the disease. The Asp727Glu polymorphism significantly ameliorates G(s)alpha protein activation in the presence of the gain-of-function mutation Ala593Asn although it is functionally inert in the context of the wild-type TSHR. Additional information on the polymorphism described.
Variant description:

Does not contribute to the genetic susceptibility to Graves disease. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs2234919 [ dbSNP | Ensembl ]

Sequence information Variant position:

52 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:

HQEEDFRVTCKDIQRIPSLP P STQTLKLIETHLRTIPSHAF 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                         HQEEDFRVTCKDIQRIPSLPPSTQTLKLIETHLRTIPSHAF

                              HQEDDFRVTCKDIHRIPTLPPSTQTLKFIETQLKTIPSRAF

Mouse                         HQEDDFRVTCKELHRIPSLPPSTQTLKLIETHLKTIPSLAF

Rat                           HQEDDFRVTCKELHQIPSLPPSTQTLKLIETHLKTIPSLAF

Pig                           HQEDDFRVTCKDIHSIPPLPPNTQTLKFIETHLKTIPSRAF

Bovine                        RQEDDFRVTCKDIQSIPSLPPSTQTLKFIETHLKTIPSRAF

Sheep                         RQEDDFRVTCKDIQRIPSLPPSTQTLKFIETHLKTIPSRAF

Cat                           HQEDDFRVTCKDIHRIPSLPPSTQTLKFIETHLKTIPSRAF

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.

Type	Positions	Description
Chain	21 – 764	Thyrotropin receptor
Topological domain	21 – 413	Extracellular

Literature citations
Association of Graves' disease with intragenic polymorphism of the thyrotropin receptor gene in a cohort of Singapore patients of multi-ethnic origins.
Ho S.-C.; Goh S.-S.; Khoo D.H.;
Thyroid 13:523-528(2003)
Cited for: ANALYSIS OF INVOLVEMENT OF VARIANTS HIS-36; THR-52 AND GLU-727 IN GRAVES DISEASE; A genomic point mutation in the extracellular domain of the thyrotropin receptor in patients with Graves' ophthalmopathy.
Bahn R.S.; Dutton C.M.; Heufelder A.E.; Sarkar G.;
J. Clin. Endocrinol. Metab. 78:256-260(1994)
Cited for: VARIANT THR-52; Resistance to thyrotropin caused by mutations in the thyrotropin-receptor gene.
Sunthornthepvarakul T.; Gottschalk M.E.; Hayashi Y.; Refetoff S.;
N. Engl. J. Med. 332:155-160(1995)
Cited for: VARIANTS CHNG1 ALA-162 AND ASN-167; VARIANT THR-52; Normal function in vivo of a homozygotic polymorphism in the human thyrotropin receptor.
Cuddihy R.M.; Bryant W.P.; Bahn R.S.;
Thyroid 5:255-257(1995)
Cited for: VARIANT THR-52; Analysis of the genetic variability of the 1st (CCC/ACC, P52T) and the 10th exons (bp 1012-1704) of the TSH receptor gene in Graves' disease.
Kaczur V.; Takacs M.; Szalai C.; Falus A.; Nagy Z.; Berencsi G.; Balazs C.;
Eur. J. Immunogenet. 27:17-23(2000)
Cited for: VARIANT THR-52; Polymorphisms in thyroid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects.
Peeters R.P.; van Toor H.; Klootwijk W.; de Rijke Y.B.; Kuiper G.G.J.M.; Uitterlinden A.G.; Visser T.J.;
J. Clin. Endocrinol. Metab. 88:2880-2888(2003)
Cited for: VARIANTS HIS-36; THR-52 AND GLU-727; ASSOCIATION WITH PLASMA TSH LEVEL; TSH receptor and Gs(alpha) genetic analysis in children with Down's syndrome and subclinical hypothyroidism.
Tonacchera M.; Perri A.; De Marco G.; Agretti P.; Montanelli L.; Banco M.E.; Corrias A.; Bellone J.; Tosi M.T.; Vitti P.; Martino E.; Pinchera A.; Chiovato L.;
J. Endocrinol. Invest. 26:997-1000(2003)
Cited for: VARIANTS HIS-36 AND THR-52; RECEPTOR GENETIC ANALYSIS IN CHILDREN WITH DOWN'S SYNDROME;

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.