UniProtKB/Swiss-Prot P01266: Variant p.Gly2375Arg

Thyroglobulin
Gene: TG
Chromosomal location: 8q24.3
Variant information

Variant position:  2375
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 Glycine (G) to Arginine (R) at position 2375 (G2375R, p.Gly2375Arg).
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 glycine (G) to large size and basic (R)
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

Involvement in disease:  Thyroid dyshormonogenesis 3 (TDH3) [MIM:274700]: A disorder due to thyroid dyshormonogenesis, causing large goiters of elastic and soft consistency in the majority of patients. Although the degree of thyroid dysfunction varies considerably among patients with defective thyroglobulin synthesis, patients usually have a relatively high serum free triiodothyronine (T3) concentration with disproportionately low free tetraiodothyronine (T4) level. The maintenance of relatively high free T3 levels prevents profound tissue hypothyroidism except in brain and pituitary, which are dependent on T4 supply, resulting in neurologic and intellectual defects in some cases. {ECO:0000269|PubMed:10199792, ECO:0000269|PubMed:16477365, ECO:0000269|PubMed:17244789, ECO:0000269|PubMed:17532758, ECO:0000269|PubMed:19509106, ECO:0000269|PubMed:27305979}. 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 TDH3.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  2375
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  2768
The length of the canonical sequence.

Location on the sequence:   GLLDQVAALTWVQTHIRGFG  G DPRRVSLAADRGGADVASIH
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                         GLLDQVAALTWVQTHIRGFGGDPRRVSLAADRGGADVASIH

Mouse                         GLLDQVAALTWVQSHIGAFGGDPQRVTLAADRSGADVASIH

Rat                           GLLDQVAALTWVQTHIGAFGGDPQRVTLAADRGGADVASIH

Bovine                        GLLDQVVALTWVQTHIQAFGGDPRRVTLAADRGGADIASIH

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 20 – 2768 Thyroglobulin


Literature citations

Thyroglobulin gene mutations producing defective intracellular transport of thyroglobulin are associated with increased thyroidal type 2 iodothyronine deiodinase activity.
Kanou Y.; Hishinuma A.; Tsunekawa K.; Seki K.; Mizuno Y.; Fujisawa H.; Imai T.; Miura Y.; Nagasaka T.; Yamada C.; Ieiri T.; Murakami M.; Murata Y.;
J. Clin. Endocrinol. Metab. 92:1451-1457(2007)
Cited for: VARIANT TDH3 ARG-2375;

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.