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UniProtKB/Swiss-Prot P16473: Variant p.Leu252Pro

Thyrotropin receptor
Gene: TSHR
Variant information

Variant position:  252
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 Leucine (L) to Proline (P) at position 252 (L252P, p.Leu252Pro).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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; displays a low expression at the cell surface and a reduced response to bovine TSH in terms of cAMP production.
Any additional useful information about the variant.



Sequence information

Variant position:  252
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:   DVSQTSVTALPSKGLEHLKE  L IARNTWTLKKLPLSLSFLHL
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                         DVSQTSVTALPSKGLEHLKELIARNTWTLKKLPLSLSFLHL

                              DVSYTSVTALPSKGLEHLKELIARNTWTLKKLPLSLSFLHL

Mouse                         DVSSTSVTALPSKGLEHLKELIAKDTWTLKKLPLSLSFLHL

Rat                           DVSSTSVTALPSKGLEHLKELIAKNTWTLKKLPLSLSFLHL

Pig                           DVSYTSVTALPPKGLEHLKELIARNTWTLKKLPLSLSFLHL

Bovine                        DISYTSVTALPSKGLEHLKELIARNTWTLRKLPLSLSFLHL

Sheep                         DISYTSVTALPSKGLEHLKELIARNTWTLKKLPLSLSFLHL

Cat                           DVSYTSVTALPSKGLEHLKELIARNTWTLKKLPLTLSFLHL

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
Repeat 250 – 271 LRR 7
Alternative sequence 232 – 274 DVSQTSVTALPSKGLEHLKELIARNTWTLKKLPLSLSFLHLTR -> VENVAVSGKGFCKSLFSWLYRLPLGRKSLSFETQKAPRSSMPS. In isoform 3.
Alternative sequence 232 – 253 DVSQTSVTALPSKGLEHLKELI -> LPLGRKSLSFETQKAPRSSMPS. In isoform Short.
Beta strand 250 – 253


Literature citations

Low prevalence of thyrotropin receptor mutations in a large series of subjects with sporadic and familial nonautoimmune subclinical hypothyroidism.
Tonacchera M.; Perri A.; De Marco G.; Agretti P.; Banco M.E.; Di Cosmo C.; Grasso L.; Vitti P.; Chiovato L.; Pinchera A.;
J. Clin. Endocrinol. Metab. 89:5787-5793(2004)
Cited for: VARIANTS CHNG1 ALA-162 AND PRO-252; CHARACTERIZATION OF VARIANT CHNG1 PRO-252;

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.