UniProtKB/Swiss-Prot P16473: Variant p.Glu727Asp

Thyrotropin receptor
Gene: TSHR
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Variant information Variant position:

727 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 Glutamate (E) to Aspartate (D) at position 727 (E727D, p.Glu727Asp). 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 acidic. 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:

Polymorphism at position 727 could be associated with Graves disease. Additional information on the polymorphism described.
Variant description:

No effect on thyroid-stimulating hormone receptor activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1991517 [ dbSNP | Ensembl ]

Sequence information Variant position:

727 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:

RGQRVPPKNSTDIQVQKVTH E MRQGLHNMEDVYELIENSHL 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                         RGQRVPPKNSTDIQVQKVTHEMRQGLHNMEDVYELIENSHL

                              RGQRVSPKNSAGIQIQKVTRDMRQSLPNMQDEYELLENSHL

Mouse                         QGQRVCPNNSTGIQIQKIPQDTRQSLPNMQDTYELLGNSQL

Rat                           QAQRVCPNNNTGIQIQKIPQDTRQSLPNVQDTYEPLGSSHL

Pig                           RGQRVSPKNSTGIQVQKVTQNMRQSLPNMQDDYELLENSHL

Bovine                        RGQRVSPKNSTGIRVQKVPPDVRQSLPNVQDDYELLENSHL

Sheep                         RGQRVSSKNSTGIRVQKVPPDVRQSLPNVQDDYELLGNSHL

Cat                           RGQRVSPKNSTGIQVQKVTRNMRQSLPNMQDDYELLENSHL

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
Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor.
Nagayama Y.; Kaufman K.D.; Seto P.; Rapoport B.;
Biochem. Biophys. Res. Commun. 165:1184-1190(1989)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG); VARIANT ASP-727; Isolation of TSH and LH/CG receptor cDNAs from human thyroid: regulation by tissue specific splicing.
Frazier A.L.; Robbins L.S.; Stork P.J.; Sprengel R.; Segaloff D.L.; Cone R.D.;
Mol. Endocrinol. 4:1264-1276(1990)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG); VARIANT ASP-727; cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org).
Kopatz S.A.; Aronstam R.S.; Sharma S.V.;
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG); VARIANT ASP-727; Further studies of genetic susceptibility to Graves' disease in a Russian population.
Chistiakov D.A.; Savost'anov K.V.; Turakulov R.I.; Petunina N.; Balabolkin M.I.; Nosikov V.V.;
Med. Sci. Monit. 8:CR180-CR184(2002)
Cited for: VARIANT ASP-727; POLYMORPHISM; A germline single nucleotide polymorphism at the intracellular domain of the human thyrotropin receptor does not have a major effect on the development of Graves' disease.
Ban Y.; Greenberg D.A.; Concepcion E.S.; Tomer Y.;
Thyroid 12:1079-1083(2002)
Cited for: VARIANT ASP-727; 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: VARIANTS HIS-36; THR-52 AND ASP-727; 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 ASP-727; Lack of association of nonautoimmune hyperfunctioning thyroid disorders and a germline polymorphism of codon 727 of the human thyrotropin receptor in a European Caucasian population.
Muehlberg T.; Herrmann K.; Joba W.; Kirchberger M.; Heberling H.-J.; Heufelder A.E.;
J. Clin. Endocrinol. Metab. 85:2640-2643(2000)
Cited for: VARIANT ASP-727; Functional significance of the thyrotropin receptor germline polymorphism D727E.
Sykiotis G.P.; Neumann S.; Georgopoulos N.A.; Sgourou A.; Papachatzopoulou A.; Markou K.B.; Kyriazopoulou V.; Paschke R.; Vagenakis A.G.; Papavassiliou A.G.;
Biochem. Biophys. Res. Commun. 301:1051-1056(2003)
Cited for: VARIANT TOXIC THYROID ADENOMA ASN-593; VARIANT ASP-727; CHARACTERIZATION OF VARIANT TOXIC THYROID ADENOMA ASN-593; CHARACTERIZATION OF VARIANT ASP-727; 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 ASP-727; ASSOCIATION WITH PLASMA TSH LEVEL;

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.