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UniProtKB/Swiss-Prot P35557: Variant p.Met210Lys

Hexokinase-4
Gene: GCK
Variant information

Variant position:  210
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 Methionine (M) to Lysine (K) at position 210 (M210K, p.Met210Lys).
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 hydrophobic (M) to large size and basic (K)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -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:  In MODY2 and PNDM1.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  210
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  465
The length of the canonical sequence.

Location on the sequence:   KRRGDFEMDVVAMVNDTVAT  M ISCYYEDHQCEVGMIVGTGC
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                         KRRGDFEMDVVAMVNDTVATMISCYYEDHQCEVGMIVGTGC

Mouse                         KRRGDFEMDVVAMVNDTVATMISCYYEDRQCEVGMIVGTGC

Rat                           KRRGDFEMDVVAMVNDTVATMISCYYEDRQCEVGMIVGTGC

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 – 465 Hexokinase-4
Domain 10 – 454 Hexokinase
Region 204 – 443 Hexokinase large subdomain
Binding site 228 – 228 ATP
Mutagenesis 197 – 197 M -> V. Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose.
Mutagenesis 211 – 211 I -> F. Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose.
Mutagenesis 214 – 214 Y -> A. Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose. No effect on affinity for ATP.
Mutagenesis 215 – 215 Y -> A. Increased glucokinase activity based on measure of catalytic efficiency. Increased affinity for glucose. Loss of inhibition by GCKR. No effect on affinity for ATP.
Helix 205 – 214


Literature citations

Neonatal diabetes mellitus due to complete glucokinase deficiency.
Njoelstad P.R.; Soevik O.; Cuesta-Munoz A.; Bjoerkhaug L.; Massa O.; Barbetti F.; Undlien D.E.; Shiota C.; Magnuson M.A.; Molven A.; Matschinsky F.M.; Bell G.I.;
N. Engl. J. Med. 344:1588-1592(2001)
Cited for: INVOLVEMENT IN PNDM1; INVOLVEMENT IN MODY2; VARIANTS MODY2 LYS-210 AND MET-228; VARIANTS PNDM1 LYS-210 AND MET-228;

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.