Incidental Mutation 'R4668:Cbl'
ID 352169
Institutional Source Beutler Lab
Gene Symbol Cbl
Ensembl Gene ENSMUSG00000034342
Gene Name Casitas B-lineage lymphoma
Synonyms Cbl-2, 4732447J05Rik, c-Cbl
Accession Numbers
Essential gene? Possibly essential (E-score: 0.503) question?
Stock # R4668 (G1)
Quality Score 225
Status Not validated
Chromosome 9
Chromosomal Location 44054273-44145346 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 44065145 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Cysteine to Serine at position 728 (C728S)
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: C684S

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000041902
Gene: ENSMUSG00000034342
AA Change: C684S

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: C711S

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: C728S

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
Predicted Effect unknown
Transcript: ENSMUST00000206258
AA Change: C27S
Predicted Effect probably benign
Transcript: ENSMUST00000206720
AA Change: C728S

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.3%
  • 20x: 95.4%
Validation Efficiency
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: 105 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4921528I07Rik A T 9: 114,133,779 (GRCm39) noncoding transcript Het
6430548M08Rik T C 8: 120,887,153 (GRCm39) probably null Het
Abca4 G A 3: 121,948,948 (GRCm39) G531E possibly damaging Het
Acad8 A G 9: 26,901,923 (GRCm39) L147P probably damaging Het
Acot10 T C 15: 20,666,028 (GRCm39) S238G probably benign Het
Adamtsl2 A T 2: 26,985,487 (GRCm39) H457L probably benign Het
Ankrd35 A T 3: 96,586,524 (GRCm39) T67S probably damaging Het
Aox1 T G 1: 58,373,853 (GRCm39) I838S possibly damaging Het
Arnt2 T C 7: 83,924,594 (GRCm39) N411S probably damaging Het
Bmpr2 T C 1: 59,906,875 (GRCm39) L656S probably damaging Het
Carns1 A T 19: 4,215,475 (GRCm39) Y902* probably null Het
Cavin1 T C 11: 100,849,622 (GRCm39) E336G probably damaging Het
Ccdc136 C A 6: 29,411,280 (GRCm39) Q218K probably damaging Het
Cdk19 C A 10: 40,342,706 (GRCm39) T196K probably damaging Het
Ceacam20 T C 7: 19,719,952 (GRCm39) Y495H probably damaging Het
Celf2 T C 2: 6,726,339 (GRCm39) I47V probably benign Het
Ces3a A C 8: 105,780,055 (GRCm39) K299T probably damaging Het
Cfap61 A T 2: 145,985,056 (GRCm39) I967F probably damaging Het
Cnksr1 C T 4: 133,960,282 (GRCm39) probably benign Het
Cped1 T C 6: 22,237,652 (GRCm39) Y923H probably benign Het
Crip3 T C 17: 46,740,290 (GRCm39) L30P probably damaging Het
Csmd1 A G 8: 16,073,905 (GRCm39) I2030T possibly damaging Het
Ctse C A 1: 131,590,487 (GRCm39) P70T probably damaging Het
Cyp2b23 A G 7: 26,372,159 (GRCm39) F429L probably damaging Het
Cyp2c66 T A 19: 39,165,100 (GRCm39) D360E probably damaging Het
D8Ertd738e A T 8: 84,976,110 (GRCm39) L46* probably null Het
Dcp2 T A 18: 44,548,429 (GRCm39) probably null Het
Ddx10 C A 9: 53,010,513 (GRCm39) D834Y possibly damaging Het
Ddx19a A T 8: 111,705,716 (GRCm39) V245E probably damaging Het
Dpf2 A C 19: 5,954,515 (GRCm39) D130E probably benign Het
Emc8 A T 8: 121,394,518 (GRCm39) M67K probably damaging Het
Ephb6 T C 6: 41,591,536 (GRCm39) L231P possibly damaging Het
Erp27 T C 6: 136,885,150 (GRCm39) E216G possibly damaging Het
Esco1 A T 18: 10,594,734 (GRCm39) I184N possibly damaging Het
Fdxacb1 T A 9: 50,681,560 (GRCm39) D11E possibly damaging Het
Fhod3 C T 18: 25,199,395 (GRCm39) P689S probably benign Het
Fnip1 T A 11: 54,394,385 (GRCm39) S940R probably damaging Het
Ganc G T 2: 120,261,548 (GRCm39) V343F probably benign Het
Gldn T A 9: 54,239,302 (GRCm39) L228* probably null Het
Gm1123 C T 9: 98,891,426 (GRCm39) R341H probably damaging Het
Gtf2f2 T C 14: 76,155,078 (GRCm39) Y161C probably benign Het
Gtf3c1 T C 7: 125,266,510 (GRCm39) T979A probably damaging Het
H4c1 A G 13: 23,944,959 (GRCm39) V61A probably benign Het
Hmcn2 G T 2: 31,325,804 (GRCm39) R4277L probably benign Het
Hsd17b6 T A 10: 127,830,295 (GRCm39) probably null Het
Igkv12-46 T C 6: 69,741,781 (GRCm39) T25A probably damaging Het
Inpp5e G A 2: 26,291,006 (GRCm39) R354C probably damaging Het
Jcad T A 18: 4,680,221 (GRCm39) probably null Het
Kcna10 G T 3: 107,102,010 (GRCm39) A214S possibly damaging Het
Kit T C 5: 75,801,880 (GRCm39) probably null Het
Kmt2a G A 9: 44,735,869 (GRCm39) probably benign Het
Lama1 T C 17: 68,059,429 (GRCm39) V604A probably benign Het
Mesd T C 7: 83,544,964 (GRCm39) V138A probably damaging Het
Mmp13 T C 9: 7,272,580 (GRCm39) F9S possibly damaging Het
Mocos T C 18: 24,799,491 (GRCm39) Y242H probably benign Het
Mrc1 A C 2: 14,298,297 (GRCm39) T718P probably damaging Het
Msh6 T C 17: 88,292,234 (GRCm39) S330P possibly damaging Het
Myh10 A G 11: 68,695,468 (GRCm39) K1532E probably damaging Het
Nat9 T C 11: 115,075,368 (GRCm39) N91S probably damaging Het
Neto2 A T 8: 86,367,691 (GRCm39) I351N probably damaging Het
Nfx1 A G 4: 40,976,367 (GRCm39) N14D possibly damaging Het
Nlrp4b A G 7: 10,448,660 (GRCm39) T288A possibly damaging Het
Nutm2 C A 13: 50,627,033 (GRCm39) T396K probably benign Het
Ogdhl A G 14: 32,054,493 (GRCm39) T196A probably benign Het
Omg T A 11: 79,393,249 (GRCm39) N203I probably damaging Het
Or52b4i A G 7: 102,191,811 (GRCm39) I223V possibly damaging Het
Or52r1b A T 7: 102,691,058 (GRCm39) D119V probably benign Het
Or5b101 A T 19: 13,005,445 (GRCm39) F83I probably benign Het
Pdgfrb A G 18: 61,197,185 (GRCm39) Y207C probably damaging Het
Pdzd7 T A 19: 45,034,126 (GRCm39) probably benign Het
Pgs1 C A 11: 117,894,333 (GRCm39) H157N probably damaging Het
Pik3c2a A G 7: 115,957,923 (GRCm39) V1121A probably benign Het
Pikfyve T A 1: 65,289,432 (GRCm39) C1235S probably damaging Het
Pms1 G A 1: 53,228,633 (GRCm39) Q872* probably null Het
Ptgs2 A G 1: 149,976,835 (GRCm39) T23A probably benign Het
Rgl1 T G 1: 152,397,122 (GRCm39) R716S probably damaging Het
Rif1 A G 2: 52,001,964 (GRCm39) E1806G probably benign Het
Ripor1 T C 8: 106,341,284 (GRCm39) V39A probably benign Het
Ryr2 G T 13: 11,608,003 (GRCm39) T868N probably benign Het
Sec22b A T 3: 97,828,438 (GRCm39) D167V probably damaging Het
Sec24d T C 3: 123,149,423 (GRCm39) V810A probably damaging Het
Shh T C 5: 28,662,853 (GRCm39) *438W probably null Het
Slc25a12 G A 2: 71,145,406 (GRCm39) S178L probably benign Het
Sorl1 A T 9: 41,895,804 (GRCm39) W1784R probably damaging Het
Sp3 A T 2: 72,801,325 (GRCm39) S229R probably damaging Het
Spata31f3 A G 4: 42,871,608 (GRCm39) F256L probably benign Het
Spdye4c G A 2: 128,434,273 (GRCm39) V5I possibly damaging Het
Spint2 A T 7: 28,959,804 (GRCm39) V53D probably damaging Het
Stard3nl T A 13: 19,560,689 (GRCm39) N29Y probably damaging Het
Stk25 A G 1: 93,553,205 (GRCm39) S299P probably damaging Het
Sult2a3 A G 7: 13,856,786 (GRCm39) S45P probably damaging Het
Thsd7a A T 6: 12,408,967 (GRCm39) V685E probably damaging Het
Tm9sf4 T A 2: 153,029,228 (GRCm39) V92D probably damaging Het
Top2b T G 14: 16,409,189 (GRCm38) I777M probably damaging Het
Topors G A 4: 40,262,669 (GRCm39) T205I probably damaging Het
Tpo T A 12: 30,153,289 (GRCm39) Y355F probably benign Het
Uba1y T A Y: 826,032 (GRCm39) M396K possibly damaging Het
Vmn1r50 A T 6: 90,084,513 (GRCm39) Q86L probably benign Het
Vmn1r77 A G 7: 11,775,358 (GRCm39) K45E probably damaging Het
Vmn2r114 A C 17: 23,529,447 (GRCm39) N218K possibly damaging Het
Vmn2r66 T A 7: 84,643,905 (GRCm39) N835I probably damaging Het
Vps54 T G 11: 21,249,989 (GRCm39) N458K probably benign Het
Zcchc7 G T 4: 44,895,964 (GRCm39) C304F probably damaging Het
Zfp335 A T 2: 164,742,206 (GRCm39) C593S probably damaging Het
Zmynd15 C G 11: 70,353,414 (GRCm39) P214R probably 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
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
R4900: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'- TCCTCGGTTTAAGCTATATCAACC -3'
(R):5'- CAGGCCTCTAGAACATGCAC -3'

Sequencing Primer
(F):5'- ATTTGCTATGCAGGCCAAGC -3'
(R):5'- GCACATCTGATCTTGTCATGAGTCAG -3'
Posted On 2015-10-08