UniProtKB/Swiss-Prot P16473: Variant p.Gln720Glu

Thyrotropin receptor
Gene: TSHR
Feedback?

Variant information Variant position:

720 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 Glutamine (Q) to Glutamate (E) at position 720 (Q720E, p.Gln720Glu). 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 polar (Q) to medium size and acidic (E) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

2 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.

Sequence information Variant position:

720 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:

KRQAQAYRGQRVPPKNSTDI Q VQKVTHDMRQGLHNMEDVYE 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                         KRQAQAYRGQRVPPKNSTDIQVQKVTHDMRQGLHNMEDVYE

                              KRQAQAYRGQRVSPKNSAGIQIQKVTRDMRQSLPNMQDEYE

Mouse                         KRQAQAYQGQRVCPNNSTGIQIQKIPQDTRQSLPNMQDTYE

Rat                           KHQAQAYQAQRVCPNNNTGIQIQKIPQDTRQSLPNVQDTYE

Pig                           KRQAQAYRGQRVSPKNSTGIQVQKVTQNMRQSLPNMQDDYE

Bovine                        KRQAQAYRGQRVSPKNSTGIRVQKVPPDVRQSLPNVQDDYE

Sheep                         KRQAQAYRGQRVSSKNSTGIRVQKVPPDVRQSLPNVQDDYE

Cat                           KRQAQAYRGQRVSPKNSTGIQVQKVTRNMRQSLPNMQDDYE

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	683 – 764	Cytoplasmic
Alternative sequence	254 – 764	Missing. In isoform Short.
Alternative sequence	275 – 764	Missing. In isoform 3.

Literature citations
Germline polymorphism of codon 727 of human thyroid-stimulating hormone receptor is associated with toxic multinodular goiter.
Gabriel E.M.; Bergert E.R.; Grant C.S.; van Heerden J.A.; Thompson G.B.; Morris J.C.;
J. Clin. Endocrinol. Metab. 84:3328-3335(1999)
Cited for: VARIANTS MET-606; GLY-703; GLU-720 AND GLU-727;

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.