Incidental Mutation 'R0068:Cbl'
ID 18024
Institutional Source Beutler Lab
Gene Symbol Cbl
Ensembl Gene ENSMUSG00000034342
Gene Name Casitas B-lineage lymphoma
Synonyms Cbl-2, 4732447J05Rik, c-Cbl
MMRRC Submission 038359-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.503) question?
Stock # R0068 (G1)
Quality Score
Status Validated
Chromosome 9
Chromosomal Location 44054273-44145346 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to T at 44065491 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Threonine at position 22 (S22T)
Gene Model predicted gene model for transcript(s): [ENSMUST00000037644] [ENSMUST00000205968] [ENSMUST00000206147] [ENSMUST00000206720]
AlphaFold P22682
Predicted Effect probably benign
Transcript: ENSMUST00000037644
AA Change: S679T

PolyPhen 2 Score 0.081 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000041902
Gene: ENSMUSG00000034342
AA Change: S679T

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: S706T

PolyPhen 2 Score 0.081 (Sensitivity: 0.93; Specificity: 0.85)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000206125
Predicted Effect probably benign
Transcript: ENSMUST00000206147
AA Change: S723T

PolyPhen 2 Score 0.010 (Sensitivity: 0.96; Specificity: 0.77)
Predicted Effect probably damaging
Transcript: ENSMUST00000206258
AA Change: S22T

PolyPhen 2 Score 0.980 (Sensitivity: 0.75; Specificity: 0.96)
Predicted Effect probably benign
Transcript: ENSMUST00000206720
AA Change: S723T

PolyPhen 2 Score 0.130 (Sensitivity: 0.93; Specificity: 0.86)
Meta Mutation Damage Score 0.0630 question?
Coding Region Coverage
  • 1x: 89.9%
  • 3x: 97.6%
  • 10x: 82.1%
  • 20x: 74.0%
Validation Efficiency 94% (83/88)
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: 57 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abca9 T C 11: 110,036,405 (GRCm39) N568S probably damaging Het
Aldoart2 G T 12: 55,612,233 (GRCm39) E53* probably null Het
Ankra2 C T 13: 98,409,891 (GRCm39) Q137* probably null Het
Arpc1a C T 5: 145,028,054 (GRCm39) T21I possibly damaging Het
Arvcf T C 16: 18,214,819 (GRCm39) probably benign Het
Ash1l C A 3: 88,914,624 (GRCm39) S1751R probably benign Het
Bltp1 A G 3: 37,006,370 (GRCm39) T1675A probably benign Het
Bsn C A 9: 107,989,336 (GRCm39) G2139C probably damaging Het
Ccdc148 T C 2: 58,717,629 (GRCm39) E530G probably benign Het
Cct3 A G 3: 88,225,772 (GRCm39) D365G probably benign Het
Cep85 A T 4: 133,881,606 (GRCm39) H332Q probably benign Het
Cwf19l1 A T 19: 44,119,938 (GRCm39) Y68N probably damaging Het
Dlc1 T A 8: 37,404,875 (GRCm39) M305L probably benign Het
Dnm1l C A 16: 16,141,883 (GRCm39) G288C probably damaging Het
Exoc7 T C 11: 116,195,732 (GRCm39) Y83C probably damaging Het
Fignl2 A T 15: 100,952,129 (GRCm39) I51N probably damaging Het
Flnb A G 14: 7,915,290 (GRCm38) N1474D possibly damaging Het
Ghrhr C T 6: 55,357,849 (GRCm39) probably benign Het
Gucy1b1 T C 3: 81,942,185 (GRCm39) T525A probably benign Het
Hhip T G 8: 80,715,885 (GRCm39) D557A probably damaging Het
Hps5 A G 7: 46,426,466 (GRCm39) probably benign Het
Igsf10 A T 3: 59,238,045 (GRCm39) V712D probably damaging Het
Irf6 G T 1: 192,848,067 (GRCm39) probably benign Het
Itpr3 T C 17: 27,323,034 (GRCm39) probably benign Het
Jag2 A G 12: 112,878,813 (GRCm39) probably benign Het
Kansl1l A G 1: 66,760,047 (GRCm39) V911A probably benign Het
Kdm3b C T 18: 34,957,827 (GRCm39) T1064I probably benign Het
Lrriq1 T A 10: 102,899,279 (GRCm39) Q1654L probably benign Het
Ltbp1 A G 17: 75,666,404 (GRCm39) T1366A probably damaging Het
Mroh1 A G 15: 76,330,892 (GRCm39) probably benign Het
Napb G A 2: 148,540,843 (GRCm39) probably benign Het
Nebl T A 2: 17,439,782 (GRCm39) R164* probably null Het
Npc1 G C 18: 12,341,424 (GRCm39) P532A probably benign Het
Nrp2 G T 1: 62,784,536 (GRCm39) K228N possibly damaging Het
Or13f5 T A 4: 52,825,503 (GRCm39) Y35* probably null Het
Plekhg1 A T 10: 3,890,502 (GRCm39) Y386F probably damaging Het
Pmfbp1 G C 8: 110,269,011 (GRCm39) probably benign Het
Poln T C 5: 34,234,432 (GRCm39) probably benign Het
Polr1c A G 17: 46,555,829 (GRCm39) V200A probably benign Het
Ppil1 A T 17: 29,471,230 (GRCm39) F92I probably damaging Het
Ptchd3 T G 11: 121,733,798 (GRCm39) L896R probably damaging Het
Rev3l A G 10: 39,700,827 (GRCm39) N1775D possibly damaging Het
Robo4 G A 9: 37,315,773 (GRCm39) R342Q probably benign Het
Rusc2 T C 4: 43,424,100 (GRCm39) probably benign Het
S100pbp T C 4: 129,038,249 (GRCm39) probably benign Het
Slc25a48 T C 13: 56,599,024 (GRCm39) V118A probably damaging Het
Slc38a10 T C 11: 120,025,679 (GRCm39) D219G probably damaging Het
Slc38a2 C T 15: 96,589,173 (GRCm39) probably null Het
Slc39a12 A G 2: 14,440,489 (GRCm39) E480G probably benign Het
Tab2 C A 10: 7,795,441 (GRCm39) R347L probably damaging Het
Tas2r123 T C 6: 132,824,955 (GRCm39) I284T possibly damaging Het
Tex9 A G 9: 72,394,051 (GRCm39) probably benign Het
Tifab A G 13: 56,324,218 (GRCm39) L75P probably damaging Het
Tmc5 T A 7: 118,233,460 (GRCm39) D91E probably benign Het
Tnks1bp1 T A 2: 84,892,696 (GRCm39) D212E probably benign Het
Ugcg A G 4: 59,217,130 (GRCm39) D218G probably benign Het
Zfp451 A T 1: 33,816,706 (GRCm39) L198I 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
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
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
Posted On 2013-03-25