UniProtKB/Swiss-Prot P01137: Variant p.Tyr81His

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

Variant position:  81
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Tyrosine (Y) to Histidine (H) at position 81 (Y81H, p.Tyr81His).
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 aromatic (Y) to medium size and polar (H)
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:  Camurati-Engelmann disease (CE) [MIM:131300]: 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. 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 CE; leads to TGF-beta-1 intracellular accumulation.
Any additional useful information about the variant.



Sequence information

Variant position:  81
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  390
The length of the canonical sequence.

Location on the sequence:   SPPSQGEVPPGPLPEAVLAL  Y NSTRDRVAGESAEPEPEPEA
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                         SPPSQGEVPPGPLPEAVLALYNST----RDRVAGESAEPEPEPE-A

Mouse                         SPPSQGEVPPGPLPEAVLALYNST----RDRVAGESADPEP

Rat                           SPPSQGEVPPGPLPEAVLALYNST----RDRVAGESADPEP

Pig                           SPPSQGDVPPGPLPEAVLALYNST----RDRVAGESVEPEP

Bovine                        SPPSQGDVPPGPLPEAILALYNST----RDRVAGESAETEP

Sheep                         SPPSQGDVPPGPLPEAILALYNST----RDRVAGESAETEP

Dog                           SPPSQGEVPPVPLPEAVLALYNST----RDRVAGESAEPEP

Horse                         SPPSQGEVPPGPLPEAVLALYNST----RAQVAGESAETEP

Xenopus laevis                KTPDV-DSEKMTVPSEAIFLYNSTLEVIREKATREEEHVGH

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 30 – 278 Latency-associated peptide
Region 75 – 271 Arm domain
Glycosylation 82 – 82 N-linked (GlcNAc...)


Literature citations

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 CE 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)
Cited for: CHARACTERIZATION OF VARIANTS CE HIS-81; CYS-218; ASP-222 AND ARG-225;

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.