UniProtKB/Swiss-Prot O75874: Variant p.Arg132Gly

Isocitrate dehydrogenase [NADP] cytoplasmic
Gene: IDH1
Chromosomal location: 2q33.3
Variant information

Variant position:  132
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Arginine (R) to Glycine (G) at position 132 (R132G, p.Arg132Gly).
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 large size and basic (R) to glycine (G)
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

Involvement in disease:  Glioma (GLM) [MIM:137800]: Gliomas are benign or malignant central nervous system neoplasms derived from glial cells. They comprise astrocytomas and glioblastoma multiforme that are derived from astrocytes, oligodendrogliomas derived from oligodendrocytes and ependymomas derived from ependymocytes. Note=The gene represented in this entry is involved in disease pathogenesis. Mutations affecting Arg-132 are tissue-specific, and suggest that this residue plays a unique role in the development of high-grade gliomas. Mutations of Arg-132 to Cys, His, Leu or Ser abolish magnesium binding and abolish the conversion of isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate. Elevated levels of R(-)-2-hydroxyglutarate are correlated with an elevated risk of malignant brain tumors.
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 a glioma sample; glioblastoma multiforme; somatic mutation.
Any additional useful information about the variant.



Sequence information

Variant position:  132
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  414
The length of the canonical sequence.

Location on the sequence:   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: 
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:  
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 Substrate
Site 139 – 139 Critical for catalysis
Modified residue 126 – 126 N6-succinyllysine
Beta strand 128 – 133


Literature citations

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; ROLE IN GLIOMAS;

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.