Incidental Mutation 'R8104:Cbl'
ID 630648
Institutional Source Beutler Lab
Gene Symbol Cbl
Ensembl Gene ENSMUSG00000034342
Gene Name Casitas B-lineage lymphoma
Synonyms Cbl-2, 4732447J05Rik, c-Cbl
MMRRC Submission 067535-MU
Accession Numbers
Essential gene? Possibly essential (E-score: 0.503) question?
Stock # R8104 (G1)
Quality Score 225.009
Status Validated
Chromosome 9
Chromosomal Location 44054273-44145346 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to A at 44069836 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Isoleucine at position 637 (S637I)
Ref Sequence ENSEMBL: ENSMUSP00000146244 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000037644] [ENSMUST00000205968] [ENSMUST00000206147] [ENSMUST00000206720]
AlphaFold P22682
Predicted Effect possibly damaging
Transcript: ENSMUST00000037644
AA Change: S593I

PolyPhen 2 Score 0.875 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000041902
Gene: ENSMUSG00000034342
AA Change: S593I

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 probably benign
Transcript: ENSMUST00000205968
AA Change: S620I

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)
Predicted Effect probably benign
Transcript: ENSMUST00000206147
AA Change: S637I

PolyPhen 2 Score 0.040 (Sensitivity: 0.94; Specificity: 0.83)
Predicted Effect probably benign
Transcript: ENSMUST00000206258
Predicted Effect probably benign
Transcript: ENSMUST00000206540
Predicted Effect possibly damaging
Transcript: ENSMUST00000206720
AA Change: S637I

PolyPhen 2 Score 0.925 (Sensitivity: 0.81; Specificity: 0.94)
Coding Region Coverage
  • 1x: 99.8%
  • 3x: 99.5%
  • 10x: 98.6%
  • 20x: 94.6%
Validation Efficiency 98% (54/55)
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: 54 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Acsbg2 C A 17: 57,152,443 (GRCm39) L666F probably benign Het
Adgrv1 A T 13: 81,588,344 (GRCm39) V4414E possibly damaging Het
Apoc3 T G 9: 46,144,585 (GRCm39) D79A probably damaging Het
Arfgap1 T A 2: 180,621,022 (GRCm39) probably null Het
Ascc1 T C 10: 59,843,551 (GRCm39) S38P probably benign Het
Asl C T 5: 130,040,791 (GRCm39) E389K probably benign Het
Atat1 A T 17: 36,215,008 (GRCm39) I215K probably benign Het
Bod1l A T 5: 41,991,075 (GRCm39) L160* probably null Het
Ccdc112 A C 18: 46,420,720 (GRCm39) S343R probably benign Het
Cr1l A G 1: 194,799,925 (GRCm39) S250P possibly damaging Het
Cspg4b T A 13: 113,456,263 (GRCm39) F770I Het
Dlgap3 A G 4: 127,129,947 (GRCm39) E907G probably damaging Het
Dsp A T 13: 38,352,600 (GRCm39) E159D probably benign Het
Ech1 G A 7: 28,524,728 (GRCm39) probably benign Het
Erbin G T 13: 103,971,485 (GRCm39) N710K possibly damaging Het
Fbxw28 A T 9: 109,155,357 (GRCm39) probably null Het
Gm4871 G C 5: 144,969,012 (GRCm39) D100E probably damaging Het
Got1l1 A G 8: 27,687,619 (GRCm39) I388T probably damaging Het
Ing5 T A 1: 93,744,166 (GRCm39) N184K probably damaging Het
Izumo3 A T 4: 92,035,145 (GRCm39) L24* probably null Het
Lig1 T C 7: 13,020,491 (GRCm39) V99A possibly damaging Het
Mbtps1 A G 8: 120,255,794 (GRCm39) Y488H possibly damaging Het
Muc5ac A G 7: 141,358,520 (GRCm39) Y1240C possibly damaging Het
Nav3 T C 10: 109,594,828 (GRCm39) T1458A probably damaging Het
Nedd1 T C 10: 92,527,778 (GRCm39) E472G probably damaging Het
Nod2 A T 8: 89,391,685 (GRCm39) H664L possibly damaging Het
Ntrk3 A G 7: 78,227,450 (GRCm39) S28P probably damaging Het
Or14a257 A G 7: 86,138,231 (GRCm39) F176S probably damaging Het
Or1i2 C T 10: 78,448,242 (GRCm39) V78I probably benign Het
Or2ag17 T A 7: 106,390,338 (GRCm39) probably benign Het
Or2ag17 C A 7: 106,390,337 (GRCm39) probably benign Het
Or6c66b T A 10: 129,376,826 (GRCm39) M140K probably benign Het
Pcdha4 G T 18: 37,087,106 (GRCm39) G430W probably damaging Het
Pcnx1 T A 12: 82,030,385 (GRCm39) Y1114* probably null Het
Pde6a T A 18: 61,364,566 (GRCm39) D207E probably damaging Het
Plekhg1 T A 10: 3,902,326 (GRCm39) I540N Het
Pnp2 A T 14: 51,197,099 (GRCm39) I62F probably benign Het
Rarg C A 15: 102,148,334 (GRCm39) D258Y probably damaging Het
Rnps1 T A 17: 24,643,484 (GRCm39) M262K unknown Het
Scaf11 T C 15: 96,316,483 (GRCm39) D1027G probably benign Het
Serpina3a A T 12: 104,079,110 (GRCm39) probably benign Het
Slc25a1 A G 16: 17,744,297 (GRCm39) probably null Het
Slc44a3 A C 3: 121,291,521 (GRCm39) V365G probably benign Het
Slc45a3 T C 1: 131,904,754 (GRCm39) F26L probably benign Het
Slc9a2 T A 1: 40,757,809 (GRCm39) I116K probably damaging Het
Stk36 T A 1: 74,665,756 (GRCm39) S700T probably benign Het
Tekt3 A G 11: 62,968,945 (GRCm39) D224G probably benign Het
Tgtp1 A T 11: 48,877,841 (GRCm39) I288N probably damaging Het
Ttn C T 2: 76,710,567 (GRCm39) V8485M unknown Het
Tubg1 G T 11: 101,014,854 (GRCm39) A199S probably benign Het
Uso1 T A 5: 92,306,280 (GRCm39) I79K probably damaging Het
Utp20 C T 10: 88,593,766 (GRCm39) D2215N probably damaging Het
Wdr43 C T 17: 71,923,350 (GRCm39) A32V probably benign Het
Zfp704 T C 3: 9,630,301 (GRCm39) D170G probably benign 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
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
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'- GAGCCTTCTCATCAGCCCTTAG -3'
(R):5'- AGGCGATTGTCCATCTAGAGAC -3'

Sequencing Primer
(F):5'- GGACTCACTTTGTAGACCAAGTTGC -3'
(R):5'- GCGATTGTCCATCTAGAGACAAACTG -3'
Posted On 2020-06-30