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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P35557: Variant p.Glu248Lys

Hexokinase-4
Gene: GCK
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Variant information Variant position: help 248 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Glutamate (E) to Lysine (K) at position 248 (E248K, p.Glu248Lys). 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: help Change from medium size and acidic (E) to large size and basic (K) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 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: help In MODY2; associated in cis with M-225; highly decreased glucokinase activity; loss of glucokinase activity when associated with M-225. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 248 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 465 The length of the canonical sequence.
Location on the sequence: help TGCNACYMEEMQNVELVEGD E GRMCVNTEWGAFGDSGELDE 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         TGCNACYMEEMQNVELVEGDEGRMCVNTEWGAFGDSGELDE

Mouse                         TGCNACYMEEMQNVELVEGDEGRMCVNTEWGAFGNSGELDE

Rat                           TGCNACYMEEMQNVELVEGDEGRMCVNTEWGAFGDSGELDE
Sequence annotation in neighborhood: help 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 – 465 Hexokinase-4
Domain 10 – 454 Hexokinase
Region 204 – 443 Hexokinase large subdomain
Binding site 228 – 228
Binding site 231 – 231
Binding site 256 – 256
Mutagenesis 256 – 256 E -> A. Inactive enzyme with no glucokinase activity.
Beta strand 248 – 254



Literature citations
Insights into the pathogenicity of rare missense GCK variants from the identification and functional characterization of compound heterozygous and double mutations inherited in cis.
Beer N.L.; Osbak K.K.; van de Bunt M.; Tribble N.D.; Steele A.M.; Wensley K.J.; Edghill E.L.; Colcough K.; Barrett A.; Valentinova L.; Rundle J.K.; Raimondo A.; Grimsby J.; Ellard S.; Gloyn A.L.;
Diabetes Care 35:1482-1484(2012)
Cited for: VARIANTS MODY2 HIS-43; ASP-68; ASN-217; MET-225; LYS-248; ARG-261 AND ARG-261; CHARACTERIZATION OF VARIANTS MODY2 HIS-43; ASP-68; ASN-217; MET-225; LYS-248; ARG-261 AND ARG-261;
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.