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UniProtKB/Swiss-Prot P36897: Variant p.Lys232Glu

TGF-beta receptor type-1
Gene: TGFBR1
Chromosomal location: 9q22
Variant information

Variant position:  232
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 Lysine (K) to Glutamate (E) at position 232 (K232E, p.Lys232Glu).
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 large size and basic (K) to medium size and acidic (E)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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:  Loeys-Dietz syndrome 1 (LDS1) [MIM:609192]: An aortic aneurysm syndrome with widespread systemic involvement, characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. Physical findings include prominent joint laxity, easy bruising, wide and atrophic scars, velvety and translucent skin with easily visible veins, spontaneous rupture of the spleen or bowel, and catastrophic complications of pregnancy, including rupture of the gravid uterus and the arteries, either during pregnancy or in the immediate postpartum period. Some patients have craniosynostosis, exotropy, micrognathia and retrognathia, structural brain abnormalities, and intellectual deficit. {ECO:0000269|PubMed:15731757, ECO:0000269|PubMed:16596670, ECO:0000269|PubMed:16791849, ECO:0000269|PubMed:16928994, ECO:0000269|PubMed:19883511, ECO:0000269|PubMed:22113417}. Note=The disease is caused by mutations affecting the gene represented in this entry. TGFBR1 mutation Gln-487 has been reported to be associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:16791849). This phenotype, also known as thoracic aortic aneurysms type 5 (AAT5), is distinguised from LDS1 by having aneurysms restricted to thoracic aorta. It is unclear, however, if this condition is fulfilled in individuals bearing Gln-487 mutation, that is why they are considered as LDS1 by the OMIM resource. {ECO:0000269|PubMed:16791849}.
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 LDS1.
Any additional useful information about the variant.

Sequence information

Variant position:  232
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  503
The length of the canonical sequence.

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.






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.

Chain 34 – 503 TGF-beta receptor type-1
Topological domain 148 – 503 Cytoplasmic
Domain 205 – 495 Protein kinase
Binding site 232 – 232 ATP
Beta strand 227 – 234

Literature citations

Aneurysm syndromes caused by mutations in the TGF-beta receptor.
Loeys B.L.; Schwarze U.; Holm T.; Callewaert B.L.; Thomas G.H.; Pannu H.; De Backer J.F.; Oswald G.L.; Symoens S.; Manouvrier S.; Roberts A.E.; Faravelli F.; Greco M.A.; Pyeritz R.E.; Milewicz D.M.; Coucke P.J.; Cameron D.E.; Braverman A.C.; Byers P.H.; De Paepe A.M.; Dietz H.C.;
N. Engl. J. Med. 355:788-798(2006)
Cited for: VARIANTS LDS1 GLU-232; TRP-487; PRO-487 AND GLN-487;

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.