Cancer Protein Description
This report provides a detailed description of a selected cancer protein with information collected from various sources, including UniProt, the Wellcome Trust Sanger Institute’s Catalogue of Somatic Mutations in Cancer (COSMIC), and the Atlas of Genetics and Cytogenetics in Oncology and Haematology.
| Protein Name: | IDH1 |
| Gene Name: | IDH1 |
| Protein Full Name: | Isocitrate dehydrogenase [NADP] cytoplasmic |
| Alias: | Cytosolic NADP-isocitrate dehydrogenase; IDH; IDHC; IDP; Isocitrate dehydrogenase 1 (NADP+) soluble; NADP+-specific ICDH; Oxalosuccinate decarboxylase; PICD |
| Mass (Da): | 46659 |
| Number AA: | 414 |
| UniProt ID: | O75874 |
| Locus ID: | 3417 |
| COSMIC ID: | IDH1 |
| Gene location on chromosome: | 2q33.3; 2q34 |
| Cancer protein type: | OP |
| Effect of cancer mutation on protein: | GAIN |
| Effect of active protein on cancer: | PROMOTES |
| Number of cancer specimens: | 70485 |
| Percent of cancer specimens with mutations: | 11.85 |
| General distribution of mutations: | Narrow |
| Location of most mutations: | One single residue (R132) shows as the major position of point mutations, without any insertions or deletions. |
| Commonly recorded point mutations: | R132H (6414); R132C (897); R132G (275); R132S (214); R132? (191); |
| Normal role description: | IDH1 is a enzyme involved in the citric acid cycle which couples the oxidative decarboxylation of isocitrate to alpha-ketoglutarate to convert NADP+/NAD+ to NADPH/NADH. IDH1 functions in a homodimeric configuration and is localized to the cytoplasm or peroxisome in cells. Mutations identified in IDH1 have been implicated in the development of colorectal cancers and gliomas. A high percentage of human glioblastomas have mutations at R132 which abolishes binding of a magnesium cofactor and alters enzyme activity to cause conversion of alpha-ketoglutarate to 2-hydroxyglutarate. 2-hydroxyglutarate has been suggested to act as a competitive to alpha-ketogluterate dioxygenases required for histone methylation which may lead to global gene expression alternations. |
| Commentary on involvement of protein in cancer: | R132 is located in the isocitrate dehydrogenase [NADP] cytoplasmic region at the substrate binding site. 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. Less than 3% mutation in autonomic ganglia, large intestine, prostate, skin, soft tissue, lymphoma. Unspecified categories: Bone; Chondrosarcoma; TRUE (29%); (74/259); Mis-sense. Brain; Not specified; TRUE (85%); (230/270); Mis-sense. Brain; primitive neuroectodermal tumour-medulloblastoma; TRUE (3%); (5/146);Mis-sense. Blood; Not specified; TRUE (100%); (2/2); Mis-sense |