UniProtKB/Swiss-Prot Q9NQC7: Variant p.Glu747Gly

Ubiquitin carboxyl-terminal hydrolase CYLD
Gene: CYLD
Chromosomal location: 16q12.1
Variant information

Variant position:  747
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 Glutamate (E) to Glycine (G) at position 747 (E747G, p.Glu747Gly).
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 acidic (E) to glycine (G)
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:  Brooke-Spiegler syndrome (BRSS) [MIM:605041]: An autosomal dominant disorder characterized by the appearance of multiple skin appendage tumors such as cylindroma, trichoepithelioma, and spiradenoma. These tumors are typically located in the head and neck region, appear in early adulthood, and gradually increase in size and number throughout life. 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.

Involvement in disease:  Multiple familial trichoepithelioma 1 (MFT1) [MIM:601606]: Autosomal dominant dermatosis characterized by the presence of many skin tumors predominantly on the face. Since histologic examination shows dermal aggregates of basaloid cells with connection to or differentiation toward hair follicles, this disorder has been thought to represent a benign hamartoma of the pilosebaceous apparatus. Trichoepitheliomas can degenerate into basal cell carcinoma. 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 MFT1 and BRSS.
Any additional useful information about the variant.



Sequence information

Variant position:  747
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  956
The length of the canonical sequence.

Location on the sequence:   VPTIQQLLEWSFINSNLKFA  E APSCLIIQMPRFGKDFKLFK
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                         VPTIQQLLEWSFINSNLKFAEAPSCLIIQMPRFGKDFKLFK

Mouse                         VPTIQQLLEWSFINSNLKFAEAPSCLIIQMPRFGKDFKLFK

Rat                           VPTIQQLLEWSFINSNLKFAEAPSCLIIQMPRFGKDFKLFK

Bovine                        VPTIQQLLECSFINSNLKFAEAPSCLIIQMPRFGKDFKLFK

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 1 – 956 Ubiquitin carboxyl-terminal hydrolase CYLD
Domain 592 – 950 USP
Beta strand 743 – 747


Literature citations

A novel missense mutation in CYLD in a family with Brooke-Spiegler syndrome.
Hu G.; Oender M.; Gill M.; Aksakal B.; Oeztas M.; Guerer M.A.; Celebi J.T.;
J. Invest. Dermatol. 121:732-734(2003)
Cited for: VARIANT MFT1 GLY-747; VARIANT BRSS GLY-747;

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.