Incidental Mutation 'B5639:Idh1'
ID 558
Institutional Source Beutler Lab
Gene Symbol Idh1
Ensembl Gene ENSMUSG00000025950
Gene Name isocitrate dehydrogenase 1 (NADP+), soluble
Synonyms IDPc, Idh-1, Id-1, E030024J03Rik
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # B5639 of strain 3d
Quality Score
Status Validated
Chromosome 1
Chromosomal Location 65197775-65225638 bp(-) (GRCm39)
Type of Mutation critical splice donor site (2 bp from exon)
DNA Base Change (assembly) A to G at 65204257 bp (GRCm39)
Zygosity Homozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000127307 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000097709] [ENSMUST00000149310] [ENSMUST00000169032] [ENSMUST00000188109] [ENSMUST00000188876]
AlphaFold O88844
Predicted Effect probably null
Transcript: ENSMUST00000097709
SMART Domains Protein: ENSMUSP00000095316
Gene: ENSMUSG00000025950

DomainStartEndE-ValueType
Iso_dh 9 401 1.05e-133 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000149310
SMART Domains Protein: ENSMUSP00000117853
Gene: ENSMUSG00000025950

DomainStartEndE-ValueType
Iso_dh 9 143 1.74e-1 SMART
Predicted Effect probably null
Transcript: ENSMUST00000169032
SMART Domains Protein: ENSMUSP00000127307
Gene: ENSMUSG00000025950

DomainStartEndE-ValueType
Iso_dh 9 401 1.05e-133 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000188109
SMART Domains Protein: ENSMUSP00000140757
Gene: ENSMUSG00000025950

DomainStartEndE-ValueType
Iso_dh 9 202 1.1e-10 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000188876
SMART Domains Protein: ENSMUSP00000139906
Gene: ENSMUSG00000025950

DomainStartEndE-ValueType
Iso_dh 9 187 2.2e-9 SMART
Meta Mutation Damage Score 0.9493 question?
Coding Region Coverage
  • 1x: 89.7%
  • 3x: 78.3%
Het Detection Efficiency 55.9%
Validation Efficiency 83% (206/248)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Isocitrate dehydrogenases catalyze the oxidative decarboxylation of isocitrate to 2-oxoglutarate. These enzymes belong to two distinct subclasses, one of which utilizes NAD(+) as the electron acceptor and the other NADP(+). Five isocitrate dehydrogenases have been reported: three NAD(+)-dependent isocitrate dehydrogenases, which localize to the mitochondrial matrix, and two NADP(+)-dependent isocitrate dehydrogenases, one of which is mitochondrial and the other predominantly cytosolic. Each NADP(+)-dependent isozyme is a homodimer. The protein encoded by this gene is the NADP(+)-dependent isocitrate dehydrogenase found in the cytoplasm and peroxisomes. It contains the PTS-1 peroxisomal targeting signal sequence. The presence of this enzyme in peroxisomes suggests roles in the regeneration of NADPH for intraperoxisomal reductions, such as the conversion of 2, 4-dienoyl-CoAs to 3-enoyl-CoAs, as well as in peroxisomal reactions that consume 2-oxoglutarate, namely the alpha-hydroxylation of phytanic acid. The cytoplasmic enzyme serves a significant role in cytoplasmic NADPH production. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2013]
PHENOTYPE: Electrophoretic variation has been shown in tissues of liver, kidney, spleen and muscle. Strains C57BL/6, C3H/He carry the a allele; DBA/2 carries the b allele; M.m. castaneus and M.m. molossinus carry the c allele; the d allele is found at low frequencyin M. m. molossinus in Japan. [provided by MGI curators]
Allele List at MGI

All alleles(14) : Targeted, other(3) Gene trapped(11)
Other mutations in this stock
Total: 15 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Dnmt1 G A 9: 20,819,264 (GRCm39) probably benign Het
Eno1 A G 4: 150,329,569 (GRCm39) probably benign Het
Ercc8 G A 13: 108,297,257 (GRCm39) G56R probably damaging Homo
Fam237b C T 5: 5,624,060 (GRCm39) probably benign Homo
Incenp G A 19: 9,871,182 (GRCm39) T149I unknown Het
Or5d16 G A 2: 87,773,942 (GRCm39) S10F probably benign Het
Or5k17 A T 16: 58,746,889 (GRCm39) I15K probably benign Homo
Pdk2 T C 11: 94,923,324 (GRCm39) D100G possibly damaging Homo
Prss56 T C 1: 87,114,892 (GRCm39) L465P probably benign Homo
Slc10a3 G A X: 73,413,145 (GRCm39) P416L probably damaging Homo
Syne2 C A 12: 75,976,564 (GRCm39) T1243K probably benign Het
Vwf T C 6: 125,619,947 (GRCm39) Y1542H probably damaging Homo
Zc3h13 G A 14: 75,553,479 (GRCm39) R302Q probably damaging Het
Zfhx4 G T 3: 5,468,235 (GRCm39) G2798W probably damaging Homo
Zfp667 A G 7: 6,293,544 (GRCm39) T15A probably damaging Het
Other mutations in Idh1
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00786:Idh1 APN 1 65,205,402 (GRCm39) missense probably damaging 1.00
IGL00790:Idh1 APN 1 65,205,281 (GRCm39) missense possibly damaging 0.94
IGL00979:Idh1 APN 1 65,210,308 (GRCm39) missense probably damaging 1.00
IGL01397:Idh1 APN 1 65,207,754 (GRCm39) missense possibly damaging 0.62
IGL02226:Idh1 APN 1 65,201,081 (GRCm39) missense probably damaging 1.00
IGL02933:Idh1 APN 1 65,201,072 (GRCm39) missense probably damaging 1.00
R0310:Idh1 UTSW 1 65,201,079 (GRCm39) missense probably damaging 1.00
R0865:Idh1 UTSW 1 65,200,315 (GRCm39) missense probably benign
R1172:Idh1 UTSW 1 65,200,319 (GRCm39) missense probably benign 0.00
R1173:Idh1 UTSW 1 65,200,319 (GRCm39) missense probably benign 0.00
R1174:Idh1 UTSW 1 65,200,319 (GRCm39) missense probably benign 0.00
R1535:Idh1 UTSW 1 65,207,697 (GRCm39) missense probably damaging 1.00
R1833:Idh1 UTSW 1 65,200,273 (GRCm39) missense probably benign
R2135:Idh1 UTSW 1 65,201,078 (GRCm39) missense probably damaging 1.00
R5434:Idh1 UTSW 1 65,214,495 (GRCm39) missense probably benign 0.00
R5478:Idh1 UTSW 1 65,200,997 (GRCm39) missense probably benign 0.04
R5633:Idh1 UTSW 1 65,204,295 (GRCm39) missense probably damaging 1.00
R6152:Idh1 UTSW 1 65,198,689 (GRCm39) missense probably damaging 1.00
R6249:Idh1 UTSW 1 65,205,378 (GRCm39) missense probably damaging 1.00
R6252:Idh1 UTSW 1 65,207,690 (GRCm39) missense probably benign
R7238:Idh1 UTSW 1 65,205,284 (GRCm39) missense probably damaging 1.00
R7754:Idh1 UTSW 1 65,198,649 (GRCm39) missense probably benign 0.00
R7819:Idh1 UTSW 1 65,204,277 (GRCm39) missense probably damaging 1.00
R8064:Idh1 UTSW 1 65,205,338 (GRCm39) missense probably damaging 1.00
R8078:Idh1 UTSW 1 65,200,225 (GRCm39) missense probably damaging 0.97
R8187:Idh1 UTSW 1 65,198,700 (GRCm39) missense probably damaging 0.98
R8778:Idh1 UTSW 1 65,204,347 (GRCm39) frame shift probably null
R8779:Idh1 UTSW 1 65,204,347 (GRCm39) frame shift probably null
R8791:Idh1 UTSW 1 65,204,347 (GRCm39) frame shift probably null
R8794:Idh1 UTSW 1 65,204,347 (GRCm39) frame shift probably null
R8795:Idh1 UTSW 1 65,204,347 (GRCm39) frame shift probably null
R8799:Idh1 UTSW 1 65,204,347 (GRCm39) frame shift probably null
R8802:Idh1 UTSW 1 65,204,347 (GRCm39) frame shift probably null
R8805:Idh1 UTSW 1 65,204,347 (GRCm39) frame shift probably null
R8935:Idh1 UTSW 1 65,204,378 (GRCm39) missense probably damaging 1.00
R9243:Idh1 UTSW 1 65,207,656 (GRCm39) critical splice donor site probably null
R9326:Idh1 UTSW 1 65,205,416 (GRCm39) missense probably damaging 1.00
Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to C transition at base pair 65211672 in the Genbank genomic region NC_000067 (Build 37.1) for the Idh1 gene on Chromosome 1 (GTAAATATAA ->GCAAATATAA).  The mutation is located within intron 5 from the ATG exon, two nucleotides from the previous exon. The Idh1 gene contains 10 total exons using Genbank record NM_001111320. Multiple transcripts of the Idh1gene are displayed on Ensembl and Vega.  The mutation has been confirmed by DNA sequencing using the Sanger method (see trace files for B5639).


    

  
    

      Protein Function and Prediction
      

	The Idh1 gene encodes a 414 amino acid protein that belongs to the isocitrate and isopropylmalate dehydrogenases family.  The enzyme is NADP-dependent and catalyzes decarboxylation of isocitrate into alpha-ketoglutarate. NADP binding occurs at residues 75-77 and 310-315. Substrate binding occurs at amino acids 94-100 (Uniprot O88844). Electrophoretic variation has been shown in tissues of liver, kidney, spleen and muscle. Strains C57BL/6, C3H/He carry the a allele; DBA/2 carries the b allele; M.m. castaneus and M.m. molossinus carry the c allele; the d allele is found at low frequency in M. m. molossinus in Japan.  Somatic mutations in the human IDH gene frequently occur in patients with glioblastoma multiforme (GBM; OMIM 137800), and are associated with increased survival of these patients.


    

  
  
  

    Posted On
    2010-11-19