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UniProtKB/Swiss-Prot P16473: Variant p.Ala553Thr

Thyrotropin receptor
Gene: TSHR
Variant information

Variant position:  553
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 Alanine (A) to Threonine (T) at position 553 (A553T, p.Ala553Thr).
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 hydrophobic (A) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Hypothyroidism, congenital, non-goitrous, 1 (CHNG1) [MIM:275200]: A non-autoimmune condition characterized by resistance to thyroid-stimulating hormone (TSH) leading to increased levels of plasma TSH and low levels of thyroid hormone. It presents variable severity depending on the completeness of the defect. Most patients are euthyroid and asymptomatic, with a normal sized thyroid gland. Only a subset of patients develop hypothyroidism and present a hypoplastic thyroid gland. {ECO:0000269|PubMed:10720030, ECO:0000269|PubMed:11095460, ECO:0000269|PubMed:11442002, ECO:0000269|PubMed:12050212, ECO:0000269|PubMed:14725684, ECO:0000269|PubMed:15531543, ECO:0000269|PubMed:25978107, ECO:0000269|PubMed:7528344, ECO:0000269|PubMed:8954020, ECO:0000269|PubMed:9100579, ECO:0000269|PubMed:9185526, ECO:0000269|PubMed:9329388}. 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 CHNG1; severe hypothyroidism.
Any additional useful information about the variant.



Sequence information

Variant position:  553
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:   IRLRHACAIMVGGWVCCFLL  A LLPLVGISSYAKVSICLPMD
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                         IRLRHACAIMVGGWVCCFLLALLPLVGISSYAKVSICLPMD

                              IRLRHAYAIMVGGWVCCFLLALLPLVGISSYAKVSICLPMD

Mouse                         IRLRHAYTIMAGGWVSCFLLALLPMVGISSYAKVSICLPMD

Rat                           IRLRHAYTIMAGGWVSCFLLALLPMVGISSYAKVSICLPMD

Pig                           IRLRHAYAIMAGGWVCCFLLALLPLVGISSYAKVSICLPMD

Bovine                        IRLWHAYVIMLGGWVCCFLLALLPLVGISSYAKVSICLPMD

Sheep                         IRLWHAYVIMLGGWVCCFLLALLPLVGISSYAKVSICLPMD

Cat                           MRLRHAYAIMVGGWVCCFLLALLPLVGISSYAKVSICLPMD

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 538 – 560 Helical; Name=4
Disulfide bond 494 – 569
Alternative sequence 254 – 764 Missing. In isoform Short.
Alternative sequence 275 – 764 Missing. In isoform 3.


Literature citations

Familial congenital hypothyroidism due to inactivating mutation of the thyrotropin receptor causing profound hypoplasia of the thyroid gland.
Abramowicz M.J.; Duprez L.; Parma J.; Vassart G.; Heinrichs C.;
J. Clin. Invest. 99:3018-3024(1997)
Cited for: VARIANT CHNG1 THR-553;

Congenital hypothyroidism and apparent athyreosis with compound heterozygosity or compensated hypothyroidism with probable hemizygosity for inactivating mutations of the TSH receptor.
Park S.-M.; Clifton-Bligh R.J.; Betts P.; Chatterjee V.K.K.;
Clin. Endocrinol. (Oxf.) 60:220-227(2004)
Cited for: VARIANT CHNG1 THR-553;

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.