UniProtKB/Swiss-Prot P01137: Variant p.Cys225Arg

Transforming growth factor beta-1
Gene: TGFB1
Chromosomal location: 19q13.1
Variant information

Variant position:  225
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 Cysteine (C) to Arginine (R) at position 225 (C225R, p.Cys225Arg).
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 (C) to large size and basic (R)
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:  Camurati-Engelmann disease (CAEND) [MIM:131300]: An autosomal dominant disorder characterized by hyperostosis and sclerosis of the diaphyses of long bones. The disease typically presents in early childhood with pain, muscular weakness and waddling gait, and in some cases other features such as exophthalmos, facial paralysis, hearing difficulties and loss of vision. {ECO:0000269|PubMed:10973241, ECO:0000269|PubMed:11062463, ECO:0000269|PubMed:12493741, ECO:0000269|PubMed:12843182, ECO:0000269|PubMed:15103729}. 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 CAEND; higher levels of active TGF-beta-1 in the culture medium.
Any additional useful information about the variant.

Sequence information

Variant position:  225
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  390
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 30 – 278 Latency-associated peptide
Region 75 – 271 Arm domain
Disulfide bond 223 – 223 Interchain (with C-225)
Disulfide bond 225 – 225 Interchain (with C-223)
Beta strand 213 – 228

Literature citations

Domain-specific mutations in TGFB1 result in Camurati-Engelmann disease.
Kinoshita A.; Saito T.; Tomita H.; Makita Y.; Yoshida K.; Ghadami M.; Yamada K.; Kondo S.; Ikegawa S.; Nishimura G.; Fukushima Y.; Nakagomi T.; Saito H.; Sugimoto T.; Kamegaya M.; Hisa K.; Murray J.C.; Taniguchi N.; Niikawa N.; Yoshiura K.;
Nat. Genet. 26:19-20(2000)
Cited for: VARIANTS CAEND CYS-218; HIS-218 AND ARG-225;

Mutations in the gene encoding the latency-associated peptide of TGF-beta 1 cause Camurati-Engelmann disease.
Janssens K.; Gershoni-Baruch R.; Guanabens N.; Migone N.; Ralston S.; Bonduelle M.; Lissens W.; Van Maldergem L.; Vanhoenacker F.; Verbruggen L.; Van Hul W.;
Nat. Genet. 26:273-275(2000)
Cited for: VARIANTS CAEND HIS-81; CYS-218 AND ARG-225;

Transforming growth factor-beta-1 mutations in Camurati-Engelmann disease lead to increased signaling by altering either activation or secretion of the mutant protein.
Janssens K.; ten Dijke P.; Ralston S.H.; Bergmann C.; Van Hul W.;
J. Biol. Chem. 278:7718-7724(2003)

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.