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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O75874: Variant p.Arg132Leu

Isocitrate dehydrogenase [NADP] cytoplasmic
Gene: IDH1
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Variant information Variant position: help 132 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help US 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 Arginine (R) to Leucine (L) at position 132 (R132L, p.Arg132Leu). 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 large size and basic (R) to medium size and hydrophobic (L) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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: help In a glioma sample; glioblastoma multiforme; somatic mutation; abolishes magnesium binding and alters enzyme activity so that isocitrate is no longer converted to alpha-ketoglutarate but instead alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 132 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 414 The length of the canonical sequence.
Location on the sequence: help IICKNIPRLVSGWVKPIIIG R HAYGDQYRATDFVVPGPGKV 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                         IICKNIPRLVSGWVKPIIIGRHAYGDQYRATDFVVPGPGKV

Mouse                         IICKNIPRLVTGWVKPIIIGRHAYGDQYRATDFVVPGPGKV

Rat                           IICKNIPRLVTGWVKPIIIGRHAYGDQYRATDFVVPGPGKV

Bovine                        IICKNIPRLVSGWVKPIIIGRHAYGDQYRATDFVVPGPGKV

Sheep                         IICKNIPRLVSGWVKPIIIGRHAYGDQYRATDFVVPGPGKV

Slime mold                    IVCKNVPRLVTCWNKSIVIGRHAFGDQYRATDFVVKGAGKL

Baker's yeast                 IIIPRIPRLVPQWEKPIIIGRHAFGDQYKATDVIVPEEGEL

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 2 – 414 Isocitrate dehydrogenase [NADP] cytoplasmic
Binding site 132 – 132 in other chain
Site 139 – 139 Critical for catalysis
Modified residue 126 – 126 N6-succinyllysine
Beta strand 128 – 133



Literature citations
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate.
Dang L.; White D.W.; Gross S.; Bennett B.D.; Bittinger M.A.; Driggers E.M.; Fantin V.R.; Jang H.G.; Jin S.; Keenan M.C.; Marks K.M.; Prins R.M.; Ward P.S.; Yen K.E.; Liau L.M.; Rabinowitz J.D.; Cantley L.C.; Thompson C.B.; Vander Heiden M.G.; Su S.M.;
Nature 462:739-744(2009)
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF VARIANT HIS-132 IN COMPLEX WITH NADP AND ALPHA-KETOGLUTARATE; FUNCTION; CATALYTIC ACTIVITY; SUBUNIT; COFACTOR; BIOPHYSICOCHEMICAL PROPERTIES; CHARACTERIZATION OF VARIANTS CYS-132; HIS-132; LEU-132 AND SER-132; INVOLVEMENT IN DISEASE; INVOLVEMENT IN GLM; IDH1 mutations at residue p.R132 (IDH1(R132)) occur frequently in high-grade gliomas but not in other solid tumors.
Bleeker F.E.; Lamba S.; Leenstra S.; Troost D.; Hulsebos T.; Vandertop W.P.; Frattini M.; Molinari F.; Knowles M.; Cerrato A.; Rodolfo M.; Scarpa A.; Felicioni L.; Buttitta F.; Malatesta S.; Marchetti A.; Bardelli A.;
Hum. Mutat. 30:7-11(2009)
Cited for: VARIANTS CYS-132; GLY-132 AND LEU-132; INVOLVEMENT IN GLM;
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.