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UniProtKB/Swiss-Prot Q16394: Variant p.Pro496Leu

Exostosin-1
Gene: EXT1
Variant information

Variant position:  496
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 Proline (P) to Leucine (L) at position 496 (P496L, p.Pro496Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
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:  Hereditary multiple exostoses 1 (EXT1) [MIM:133700]: EXT is a genetically heterogeneous bone disorder caused by genes segregating on human chromosomes 8, 11, and 19 and designated EXT1, EXT2 and EXT3 respectively. EXT is a dominantly inherited skeletal disorder primarily affecting endochondral bone during growth. The disease is characterized by formation of numerous cartilage-capped, benign bone tumors (osteocartilaginous exostoses or osteochondromas) that are often accompanied by skeletal deformities and short stature. In a small percentage of cases exostoses have exhibited malignant transformation resulting in an osteosarcoma or chondrosarcoma. Osteochondromas development can also occur as a sporadic event. {ECO:0000269|PubMed:10441575, ECO:0000269|PubMed:10480354, ECO:0000269|PubMed:11169766, ECO:0000269|PubMed:8981950, ECO:0000269|PubMed:9326317, ECO:0000269|PubMed:9463333, ECO:0000269|PubMed:9521425, ECO:0000269|Ref.10}. 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 EXT1; no loss of activity.
Any additional useful information about the variant.



Sequence information

Variant position:  496
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  746
The length of the canonical sequence.

Location on the sequence:   PPSKFTAVIHAVTPLVSQSQ  P VLKLLVAAAKSQYCAQIIVL
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                         PPSKFTAVIHA-VTPLVSQSQPVLKLLVAAAKSQYCAQIIVL

Mouse                         PPSKFTAVIHA-VTPLVSQSQPVLKLLVAAAKSQYCAQIIV

Bovine                        PPSKFTAVIHA-VTPLVSQSQPVLKLLVAAAKSQYCAQIIV

Caenorhabditis elegans        -----------------------------------------

Drosophila                    PRHNYTAVIYVQIGAALGPNAALYKLVRTITKSQFVERILV

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 – 746 Exostosin-1
Topological domain 29 – 746 Lumenal
Mutagenesis 486 – 486 A -> H. No effect on heparan-sulfate biosynthesis.
Mutagenesis 486 – 486 Missing. No effect on heparan-sulfate biosynthesis.
Mutagenesis 496 – 496 P -> H. No effect on heparan-sulfate biosynthesis.
Mutagenesis 496 – 496 Missing. No effect on heparan-sulfate biosynthesis.


Literature citations

Mutation analysis of hereditary multiple exostoses in the Chinese.
Xu L.; Xia J.; Jiang H.; Zhou J.; Li H.; Wang D.; Pan Q.; Long Z.; Fan C.; Deng H.-X.;
Hum. Genet. 105:45-50(1999)
Cited for: VARIANTS EXT1 VAL-486 AND LEU-496;

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.