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UniProtKB/Swiss-Prot P07949: Variant p.Glu762Gln

Proto-oncogene tyrosine-protein kinase receptor Ret
Gene: RET
Variant information

Variant position:  762
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  LP/P [Disclaimer]
The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance

Residue change:  From Glutamate (E) to Glutamine (Q) at position 762 (E762Q, p.Glu762Gln).
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 medium size and polar (Q)
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

Variant description:  In HSCR1; sporadic form.
Any additional useful information about the variant.

Sequence information

Variant position:  762
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1114
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 29 – 1114 Proto-oncogene tyrosine-protein kinase receptor Ret
Chain 708 – 1017 Soluble RET kinase fragment
Topological domain 658 – 1114 Cytoplasmic
Domain 724 – 1016 Protein kinase
Binding site 758 – 758 ATP
Mutagenesis 708 – 1114 Missing. Loss of induced cell death, but increased cell aggregation.
Mutagenesis 758 – 758 K -> R. Loss of kinase activity. No effect on interaction with and dissociation from CBLC and CD2AP.

Literature citations

Heterogeneity and low detection rate of RET mutations in Hirschsprung disease.
Yin L.; Barone V.; Seri M.; Bolino A.; Bocciardi R.; Ceccherini I.; Pasini B.; Tocco T.; Lerone M.; Cywes S.; Moore S.; Vanderwinden J.-M.; Abramowicz M.J.; Kristoffersson U.; Larsson L.T.; Hamel B.C.J.; Silengo M.; Martucciello G.; Romeo G.;
Eur. J. Hum. Genet. 2:272-280(1994)
Cited for: VARIANTS HSCR1 PRO-40; LEU-399; GLN-762; PRO-765; GLN-897; GLY-972 AND LEU-973;

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.