Incidental Mutation 'N/A - 293:Kras'
ID 25
Institutional Source Beutler Lab
Gene Symbol Kras
Ensembl Gene ENSMUSG00000030265
Gene Name Kirsten rat sarcoma viral oncogene homolog
Synonyms Kras2, Kras-2, K-ras, Ki-ras
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # N/A - 293 of strain aoba
Quality Score
Status Validated
Chromosome 6
Chromosomal Location 145162425-145195965 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 145177940 bp (GRCm39)
Zygosity Homozygous
Amino Acid Change Methionine to Leucine at position 111 (M111L)
Ref Sequence ENSEMBL: ENSMUSP00000107339 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000032399] [ENSMUST00000111710] [ENSMUST00000156486] [ENSMUST00000203147]
AlphaFold P32883
Predicted Effect probably benign
Transcript: ENSMUST00000032399
AA Change: M111L

PolyPhen 2 Score 0.006 (Sensitivity: 0.97; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000032399
Gene: ENSMUSG00000030265
AA Change: M111L

DomainStartEndE-ValueType
RAS 1 166 1.14e-123 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000111710
AA Change: M111L

PolyPhen 2 Score 0.006 (Sensitivity: 0.97; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000107339
Gene: ENSMUSG00000030265
AA Change: M111L

DomainStartEndE-ValueType
RAS 1 166 3.7e-123 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000123972
Predicted Effect probably benign
Transcript: ENSMUST00000156486
Predicted Effect probably benign
Transcript: ENSMUST00000203147
SMART Domains Protein: ENSMUSP00000145294
Gene: ENSMUSG00000030265

DomainStartEndE-ValueType
small_GTPase 1 53 3.1e-8 SMART
Meta Mutation Damage Score 0.1339 question?
Coding Region Coverage
  • 1x: 88.4%
  • 3x: 74.0%
Validation Efficiency 85% (165/193)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene, a Kirsten ras oncogene homolog from the mammalian ras gene family, encodes a protein that is a member of the small GTPase superfamily. A single amino acid substitution is responsible for an activating mutation. The transforming protein that results is implicated in various malignancies, including lung adenocarcinoma, mucinous adenoma, ductal carcinoma of the pancreas and colorectal carcinoma. Alternative splicing leads to variants encoding two isoforms that differ in the C-terminal region. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a null allele exhibit embryonic lethality, decreased fetal growth, pericardial edema, anemia, and liver hypoplasia. Mice heterozygous for various knock-in alleles exhibit increased tumorigenesis. [provided by MGI curators]
Allele List at MGI

All alleles(26) : Targeted, knock-out(3) Targeted, other(7) Gene trapped(14) Other(2)

Other mutations in this stock
Total: 8 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Exoc1l T C 5: 76,664,339 (GRCm39) S143P probably benign Homo
Gm7634 T A 1: 16,124,084 (GRCm39) noncoding transcript Homo
Lrig1 T C 6: 94,586,068 (GRCm39) T707A probably benign Homo
Mycbp2 A G 14: 103,461,898 (GRCm39) probably benign Homo
Or2a7 C T 6: 43,151,493 (GRCm39) T191I probably benign Homo
Smarcad1 T A 6: 65,051,898 (GRCm39) F344I probably benign Homo
Sprr4 G A 3: 92,407,650 (GRCm39) Q51* probably null Homo
Zeb1 A T 18: 5,767,076 (GRCm39) H529L possibly damaging Homo
Other mutations in Kras
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00808:Kras APN 6 145,192,474 (GRCm39) missense probably damaging 1.00
IGL02929:Kras APN 6 145,177,815 (GRCm39) intron probably benign
R1463:Kras UTSW 6 145,170,787 (GRCm39) intron probably benign
R1518:Kras UTSW 6 145,177,977 (GRCm39) missense probably benign 0.00
R1603:Kras UTSW 6 145,170,871 (GRCm39) nonsense probably null
R1885:Kras UTSW 6 145,177,843 (GRCm39) missense probably damaging 1.00
R5089:Kras UTSW 6 145,170,869 (GRCm39) missense probably benign 0.00
R5133:Kras UTSW 6 145,177,879 (GRCm39) missense probably benign 0.00
R7710:Kras UTSW 6 145,166,354 (GRCm39) missense probably benign
R7876:Kras UTSW 6 145,170,848 (GRCm39) missense probably benign
R8151:Kras UTSW 6 145,166,360 (GRCm39) small deletion probably benign
R8944:Kras UTSW 6 145,170,853 (GRCm39) missense probably benign
R8951:Kras UTSW 6 145,166,338 (GRCm39) missense probably benign
R9345:Kras UTSW 6 145,192,442 (GRCm39) missense probably benign 0.00
Z1177:Kras UTSW 6 145,192,498 (GRCm39) missense probably damaging 1.00
Nature of Mutation
DNA sequencing using the SOLiD technique identified an A to T transversion at position 522 of the Kras transcript, in exon 4 of 5 total exons. Multiple Kras transcripts are displayed on Ensembl. The mutated nucleotide causes a methionine to leucine substitution at amino acid 111 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
Protein Function and Prediction
Kras encodes the 189 amino acid GTPase KRas protein (also known as K-Ras 2). In the mature form of the protein, the last three amino acids are removed. Ras proteins bind GDP/GTP and possess intrinsic GTPase activity. Ras proteins alternate between a GTP-bound on state and a GDP-bound off state. In their on state, they activate effector molecules such as adenylate cyclase. In the GTPase KRas protein, nucleotide binding occurs at amino acids 10-17, 57-61, and 116-119. The effector domain, which activates the effector molecule, occurs at amino acids 32-40.  Two isoforms of GTPase KRas are displayed on Uniprot and differ in their C-terminal regions (Uniprot P32883). Homozygous knockout mice for the Kras gene display embryonic lethality and exhibit a wide range of developmental defects.
 
The E111G mutation is predicted to be benign by the PolyPhen program.
Posted On 2009-11-10