Incidental Mutation 'R4900:Cbl'
ID 376099
Institutional Source Beutler Lab
Gene Symbol Cbl
Ensembl Gene ENSMUSG00000034342
Gene Name Casitas B-lineage lymphoma
Synonyms Cbl-2, 4732447J05Rik, c-Cbl
MMRRC Submission 042504-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.503) question?
Stock # R4900 (G1)
Quality Score 225
Status Validated
Chromosome 9
Chromosomal Location 44054273-44145346 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 44064166 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Alanine at position 790 (V790A)
Ref Sequence ENSEMBL: ENSMUSP00000146244 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000037644] [ENSMUST00000205968] [ENSMUST00000206147] [ENSMUST00000206720]
AlphaFold P22682
Predicted Effect probably benign
Transcript: ENSMUST00000037644
AA Change: V746A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000041902
Gene: ENSMUSG00000034342
AA Change: V746A

DomainStartEndE-ValueType
low complexity region 8 23 N/A INTRINSIC
low complexity region 34 46 N/A INTRINSIC
Pfam:Cbl_N 49 173 9.4e-59 PFAM
Pfam:Cbl_N2 177 260 4.7e-44 PFAM
Pfam:Cbl_N3 262 347 7.2e-48 PFAM
RING 379 417 1.04e-7 SMART
low complexity region 454 463 N/A INTRINSIC
low complexity region 530 549 N/A INTRINSIC
UBA 864 901 3.17e-8 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000205313
Predicted Effect probably benign
Transcript: ENSMUST00000205968
AA Change: V773A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000206125
Predicted Effect probably benign
Transcript: ENSMUST00000206147
AA Change: V790A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
Predicted Effect probably benign
Transcript: ENSMUST00000206258
Predicted Effect probably benign
Transcript: ENSMUST00000206720
AA Change: V790A

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
Meta Mutation Damage Score 0.0660 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.4%
  • 10x: 96.5%
  • 20x: 93.1%
Validation Efficiency 100% (84/84)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a proto-oncogene that encodes a RING finger E3 ubiquitin ligase. The encoded protein is one of the enzymes required for targeting substrates for degradation by the proteasome. This protein mediates the transfer of ubiquitin from ubiquitin conjugating enzymes (E2) to specific substrates. This protein also contains an N-terminal phosphotyrosine binding domain that allows it to interact with numerous tyrosine-phosphorylated substrates and target them for proteasome degradation. As such it functions as a negative regulator of many signal transduction pathways. This gene has been found to be mutated or translocated in many cancers including acute myeloid leukaemia, and expansion of CGG repeats in the 5' UTR has been associated with Jacobsen syndrome. Mutations in this gene are also the cause of Noonan syndrome-like disorder. [provided by RefSeq, Jul 2016]
PHENOTYPE: Homozygotes for targeted null mutations exhibit increased thymic CD3 and CD4 expression and tyrosine-phosphorylation, lymphoid hyperplasia, and altered splenic hemopoiesis. Females show increased ductal density and branching in mammary fat pads. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 77 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4930590J08Rik T C 6: 91,895,091 (GRCm39) V262A probably benign Het
Abtb2 A G 2: 103,397,349 (GRCm39) E93G possibly damaging Het
Adam5 A C 8: 25,232,172 (GRCm39) probably null Het
Adam5 G A 8: 25,271,619 (GRCm39) T596I probably damaging Het
Adgrb2 T A 4: 129,907,668 (GRCm39) Y1001N probably damaging Het
Aox1 T G 1: 58,344,544 (GRCm39) S546A probably benign Het
Asic2 T C 11: 81,464,280 (GRCm39) probably benign Het
Bcl11b T A 12: 107,955,957 (GRCm39) N64I probably damaging Het
Cacna1g A G 11: 94,350,177 (GRCm39) F556S possibly damaging Het
Cd300c2 A T 11: 114,891,807 (GRCm39) C22* probably null Het
Cdh11 C T 8: 103,374,090 (GRCm39) probably null Het
Ces2g C T 8: 105,693,989 (GRCm39) Q442* probably null Het
Cps1 A T 1: 67,200,063 (GRCm39) T404S probably damaging Het
Csf2rb2 A T 15: 78,170,174 (GRCm39) probably null Het
Csmd2 A G 4: 128,346,318 (GRCm39) Y1526C probably benign Het
Cyp2a12 C T 7: 26,730,640 (GRCm39) Q202* probably null Het
Cyp2c39 G A 19: 39,502,020 (GRCm39) M136I probably benign Het
Cyp2j13 G A 4: 95,947,280 (GRCm39) T257I probably damaging Het
Dnah8 T A 17: 30,965,949 (GRCm39) L2427Q probably damaging Het
Dop1b G T 16: 93,560,318 (GRCm39) probably null Het
Entrep1 A G 19: 23,952,790 (GRCm39) S507P possibly damaging Het
Epcam T C 17: 87,951,049 (GRCm39) V212A possibly damaging Het
Flt1 C A 5: 147,620,749 (GRCm39) A132S probably benign Het
Flvcr2 T A 12: 85,829,756 (GRCm39) V255D probably damaging Het
Galc G T 12: 98,197,731 (GRCm39) T326K probably damaging Het
Gas2l3 CACTCGTCATACT CACT 10: 89,266,820 (GRCm39) probably benign Het
Gen1 A T 12: 11,291,561 (GRCm39) Y808N probably benign Het
Glis1 C T 4: 107,476,761 (GRCm39) A306V probably damaging Het
Gm10638 A G 8: 87,473,028 (GRCm39) probably benign Het
Gm12789 G A 4: 101,846,182 (GRCm39) probably benign Het
Gm27048 C T 8: 81,661,228 (GRCm39) noncoding transcript Het
Gm4204 T C 1: 135,160,556 (GRCm39) noncoding transcript Het
Gm904 A T 13: 50,799,325 (GRCm39) I95F possibly damaging Het
Gvin3 T G 7: 106,197,793 (GRCm39) noncoding transcript Het
Hjurp GT GTT 1: 88,194,246 (GRCm39) probably null Het
Ints11 G A 4: 155,972,887 (GRCm39) D526N probably benign Het
Itfg2 A G 6: 128,393,279 (GRCm39) probably benign Het
Jund T C 8: 71,152,254 (GRCm39) V183A probably damaging Het
Kcnj8 A G 6: 142,512,221 (GRCm39) S129P probably damaging Het
Kcnq3 A G 15: 65,867,259 (GRCm39) S795P probably damaging Het
Lhx8 G T 3: 154,035,925 (GRCm39) A22E probably benign Het
Lrp8 A G 4: 107,664,006 (GRCm39) probably benign Het
Lvrn G T 18: 47,026,768 (GRCm39) A789S probably damaging Het
Lvrn T C 18: 47,014,479 (GRCm39) S526P probably damaging Het
Mga T A 2: 119,794,535 (GRCm39) C2622S possibly damaging Het
Mroh8 T C 2: 157,070,647 (GRCm39) E568G probably benign Het
Ms4a4b C A 19: 11,440,503 (GRCm39) probably benign Het
Muc2 T C 7: 141,303,280 (GRCm39) F99S probably benign Het
Myo5c T A 9: 75,180,825 (GRCm39) I738N probably damaging Het
Naip6 A C 13: 100,433,477 (GRCm39) V1120G probably damaging Het
Ncl T C 1: 86,283,901 (GRCm39) T307A probably benign Het
Npr1 A T 3: 90,363,272 (GRCm39) D869E possibly damaging Het
Nup93 A G 8: 95,013,231 (GRCm39) T36A probably benign Het
Olfml2b C A 1: 170,489,947 (GRCm39) T189N probably damaging Het
Or4c12b A G 2: 89,647,312 (GRCm39) N208S possibly damaging Het
Or8b9 T C 9: 37,766,608 (GRCm39) F165L probably benign Het
P4htm A C 9: 108,456,427 (GRCm39) W458G probably damaging Het
Pdzrn4 G T 15: 92,668,638 (GRCm39) R930L probably damaging Het
Pgam5 G A 5: 110,408,301 (GRCm39) A240V probably damaging Het
Prex2 T C 1: 11,220,129 (GRCm39) probably benign Het
Ptpru T G 4: 131,515,693 (GRCm39) E897A probably damaging Het
Rapgef2 A T 3: 78,981,670 (GRCm39) N1256K probably benign Het
Rhbdl3 A G 11: 80,210,439 (GRCm39) E64G probably benign Het
Sel1l3 A T 5: 53,289,184 (GRCm39) L879Q probably damaging Het
Siah1a G T 8: 87,451,703 (GRCm39) D260E probably benign Het
Skint6 T C 4: 112,924,667 (GRCm39) I522V probably benign Het
Slco4c1 G A 1: 96,768,953 (GRCm39) P303L probably damaging Het
Smok3c T C 5: 138,062,813 (GRCm39) I100T probably damaging Het
Snx24 C A 18: 53,518,295 (GRCm39) Y141* probably null Het
Tigit A G 16: 43,469,594 (GRCm39) S166P probably damaging Het
Tmem183a C T 1: 134,275,904 (GRCm39) R324Q probably benign Het
Tmie T C 9: 110,696,001 (GRCm39) D130G possibly damaging Het
Uggt1 G A 1: 36,241,936 (GRCm39) R333* probably null Het
Vmn2r111 T C 17: 22,767,637 (GRCm39) N620S possibly damaging Het
Vmn2r12 T A 5: 109,240,852 (GRCm39) N87I probably damaging Het
Vmn2r92 A G 17: 18,404,605 (GRCm39) D583G probably benign Het
Zdhhc17 T C 10: 110,821,819 (GRCm39) D60G possibly damaging Het
Other mutations in Cbl
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00590:Cbl APN 9 44,112,495 (GRCm39) missense probably damaging 1.00
IGL01369:Cbl APN 9 44,112,358 (GRCm39) nonsense probably null
IGL01434:Cbl APN 9 44,075,503 (GRCm39) missense probably damaging 0.99
IGL01866:Cbl APN 9 44,065,122 (GRCm39) nonsense probably null
IGL02326:Cbl APN 9 44,062,770 (GRCm39) missense possibly damaging 0.94
IGL02956:Cbl APN 9 44,080,331 (GRCm39) missense probably damaging 1.00
Bungalow UTSW 9 44,112,416 (GRCm39) missense probably damaging 1.00
Casita UTSW 9 44,075,462 (GRCm39) missense probably damaging 1.00
tiny_house UTSW 9 44,075,449 (GRCm39) missense probably damaging 1.00
R0068:Cbl UTSW 9 44,065,491 (GRCm39) missense probably damaging 0.98
R0390:Cbl UTSW 9 44,112,302 (GRCm39) missense probably damaging 1.00
R0655:Cbl UTSW 9 44,070,049 (GRCm39) missense probably damaging 1.00
R0764:Cbl UTSW 9 44,075,449 (GRCm39) missense probably damaging 1.00
R1466:Cbl UTSW 9 44,065,541 (GRCm39) missense probably benign 0.10
R1466:Cbl UTSW 9 44,065,541 (GRCm39) missense probably benign 0.10
R1616:Cbl UTSW 9 44,064,197 (GRCm39) missense probably damaging 0.99
R1736:Cbl UTSW 9 44,064,192 (GRCm39) missense possibly damaging 0.80
R1808:Cbl UTSW 9 44,075,526 (GRCm39) missense probably damaging 1.00
R1865:Cbl UTSW 9 44,075,462 (GRCm39) missense probably damaging 1.00
R3156:Cbl UTSW 9 44,070,147 (GRCm39) missense possibly damaging 0.74
R3431:Cbl UTSW 9 44,062,743 (GRCm39) makesense probably null
R4668:Cbl UTSW 9 44,065,145 (GRCm39) missense probably benign 0.00
R4700:Cbl UTSW 9 44,084,677 (GRCm39) missense probably damaging 1.00
R4866:Cbl UTSW 9 44,064,166 (GRCm39) missense probably benign 0.00
R4995:Cbl UTSW 9 44,065,108 (GRCm39) missense possibly damaging 0.62
R5014:Cbl UTSW 9 44,065,696 (GRCm39) splice site probably null
R5324:Cbl UTSW 9 44,065,551 (GRCm39) missense probably damaging 0.97
R5353:Cbl UTSW 9 44,084,620 (GRCm39) missense probably damaging 1.00
R5382:Cbl UTSW 9 44,070,318 (GRCm39) missense probably benign
R5747:Cbl UTSW 9 44,112,416 (GRCm39) missense probably damaging 1.00
R5834:Cbl UTSW 9 44,145,076 (GRCm39) missense probably damaging 1.00
R6307:Cbl UTSW 9 44,069,809 (GRCm39) critical splice donor site probably null
R6755:Cbl UTSW 9 44,084,671 (GRCm39) missense probably damaging 0.98
R7393:Cbl UTSW 9 44,065,485 (GRCm39) critical splice donor site probably null
R7779:Cbl UTSW 9 44,070,393 (GRCm39) missense probably benign
R7789:Cbl UTSW 9 44,074,764 (GRCm39) missense probably damaging 1.00
R8094:Cbl UTSW 9 44,074,696 (GRCm39) missense probably benign 0.03
R8104:Cbl UTSW 9 44,069,836 (GRCm39) missense possibly damaging 0.93
R8146:Cbl UTSW 9 44,076,171 (GRCm39) missense probably damaging 1.00
R8340:Cbl UTSW 9 44,070,297 (GRCm39) missense possibly damaging 0.77
R8424:Cbl UTSW 9 44,064,151 (GRCm39) missense possibly damaging 0.51
R8920:Cbl UTSW 9 44,078,570 (GRCm39) missense probably damaging 0.99
R9185:Cbl UTSW 9 44,064,137 (GRCm39) missense probably damaging 1.00
X0057:Cbl UTSW 9 44,145,064 (GRCm39) small deletion probably benign
Predicted Primers PCR Primer
(F):5'- CAGCTTTCCAACATATAGATCCAGG -3'
(R):5'- GCTGCCTCTGGATTGAAGTG -3'

Sequencing Primer
(F):5'- CTACTCACTGACTTATTGACACGAG -3'
(R):5'- CCTCTGGATTGAAGTGTGTTGGAAAG -3'
Posted On 2016-03-17