Mutagenetix > Incidental Mutation

Incidental Mutation 'R0390:Cbl'

31612

Institutional Source

Beutler Lab

Gene Symbol

Cbl

Ensembl Gene

ENSMUSG00000034342

Gene Name

Casitas B-lineage lymphoma

Synonyms

Cbl-2, 4732447J05Rik, c-Cbl

MMRRC Submission

038596-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.520) question?

Stock #

R0390 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

44054273-44145346 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 44112302 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Phenylalanine to Serine at position 131 (F131S)

Ref Sequence

ENSEMBL: ENSMUSP00000146244 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000037644] [ENSMUST00000205755] [ENSMUST00000205968] [ENSMUST00000206147] [ENSMUST00000206720]

AlphaFold

P22682

Predicted Effect

probably damaging
Transcript: ENSMUST00000037644
AA Change: F131S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000041902
Gene: ENSMUSG00000034342
AA Change: F131S

Domain	Start	End	E-Value	Type
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 damaging
Transcript: ENSMUST00000205755
AA Change: F28S

PolyPhen 2 Score 0.988 (Sensitivity: 0.73; Specificity: 0.96)

Predicted Effect

probably damaging
Transcript: ENSMUST00000205968
AA Change: F131S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

Predicted Effect

probably damaging
Transcript: ENSMUST00000206147
AA Change: F131S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

Predicted Effect

probably damaging
Transcript: ENSMUST00000206720
AA Change: F131S

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

Meta Mutation Damage Score

0.9739

Coding Region Coverage

1x: 99.1%
3x: 98.1%
10x: 95.9%
20x: 92.0%

Validation Efficiency

98% (110/112)

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: 110 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam18	C	T	8: 25,164,070 (GRCm39)	G38R	probably benign	Het
Ap2m1	T	C	16: 20,359,849 (GRCm39)	M183T	probably damaging	Het
Apob	A	T	12: 8,038,678 (GRCm39)	I364F	probably damaging	Het
Arl6	A	T	16: 59,442,784 (GRCm39)		probably benign	Het
Cand2	A	G	6: 115,751,614 (GRCm39)	M15V	possibly damaging	Het
Ccdc74a	A	G	16: 17,468,340 (GRCm39)	S321G	probably benign	Het
Cdc14b	T	C	13: 64,358,006 (GRCm39)		probably benign	Het
Cep152	T	C	2: 125,418,789 (GRCm39)		probably benign	Het
Cep290	A	G	10: 100,344,620 (GRCm39)	E479G	probably benign	Het
Chrm2	T	G	6: 36,501,046 (GRCm39)	I301R	probably benign	Het
Clec2e	A	G	6: 129,070,431 (GRCm39)	W197R	probably damaging	Het
Cnot10	G	T	9: 114,458,218 (GRCm39)	S96*	probably null	Het
Col19a1	A	G	1: 24,328,736 (GRCm39)		probably benign	Het
Csmd2	T	C	4: 128,027,466 (GRCm39)		probably benign	Het
Cthrc1	A	T	15: 38,950,159 (GRCm39)	*172L	probably null	Het
Cul9	A	T	17: 46,839,515 (GRCm39)	I821N	probably benign	Het
Daam1	G	C	12: 72,022,078 (GRCm39)		probably benign	Het
Dhx58	A	T	11: 100,590,090 (GRCm39)	I398N	probably damaging	Het
Dip2b	T	A	15: 100,091,794 (GRCm39)	H844Q	probably damaging	Het
Dmac2	A	G	7: 25,320,454 (GRCm39)	D50G	probably damaging	Het
Dmxl1	C	A	18: 50,012,429 (GRCm39)	Q1529K	probably benign	Het
Dtna	C	T	18: 23,730,558 (GRCm39)	P315L	probably damaging	Het
Ep300	T	C	15: 81,524,317 (GRCm39)	S1382P	unknown	Het
Fat2	A	T	11: 55,201,603 (GRCm39)	N490K	probably damaging	Het
Flg2	T	A	3: 93,107,662 (GRCm39)		probably benign	Het
Gpatch1	T	C	7: 34,980,806 (GRCm39)		probably benign	Het
Grin2a	C	A	16: 9,397,449 (GRCm39)	K879N	possibly damaging	Het
Hacd3	A	C	9: 64,908,304 (GRCm39)	I164S	possibly damaging	Het
Hinfp	A	C	9: 44,210,245 (GRCm39)	C197G	probably damaging	Het
Hsd17b12	T	C	2: 93,945,335 (GRCm39)		probably benign	Het
Hsd3b1	A	T	3: 98,760,355 (GRCm39)	L212Q	probably damaging	Het
Ifrd1	C	T	12: 40,264,093 (GRCm39)		probably null	Het
Igf2bp2	A	G	16: 21,900,551 (GRCm39)	F129L	possibly damaging	Het
Kirrel3	T	A	9: 34,931,459 (GRCm39)	I409N	probably damaging	Het
Klhdc10	T	C	6: 30,447,411 (GRCm39)	I204T	probably damaging	Het
Kpna6	A	T	4: 129,551,597 (GRCm39)	S65R	possibly damaging	Het
Lama3	A	T	18: 12,540,620 (GRCm39)	D308V	probably benign	Het
Larp4b	T	A	13: 9,208,143 (GRCm39)		probably null	Het
Lgr6	C	T	1: 134,921,748 (GRCm39)	A199T	probably damaging	Het
Lyzl1	A	T	18: 4,169,175 (GRCm39)	T11S	probably benign	Het
Man1c1	A	G	4: 134,305,626 (GRCm39)	L366P	probably damaging	Het
Mef2a	A	G	7: 66,901,472 (GRCm39)	M100T	probably damaging	Het
Mettl13	G	A	1: 162,366,458 (GRCm39)	H474Y	possibly damaging	Het
Minar2	T	A	18: 59,208,760 (GRCm39)	V136E	probably damaging	Het
Mmp3	A	G	9: 7,451,320 (GRCm39)	D352G	probably benign	Het
Mns1	T	C	9: 72,360,086 (GRCm39)	I412T	probably damaging	Het
Mon2	T	C	10: 122,842,926 (GRCm39)	D1501G	probably null	Het
Mylk	G	T	16: 34,695,990 (GRCm39)	G242W	probably damaging	Het
Nav1	T	C	1: 135,377,704 (GRCm39)	D1715G	possibly damaging	Het
Nckap1l	T	C	15: 103,362,310 (GRCm39)	S2P	probably damaging	Het
Nek3	A	T	8: 22,618,745 (GRCm39)		probably benign	Het
Nfrkb	A	G	9: 31,300,193 (GRCm39)		probably benign	Het
Nlrp4d	T	C	7: 10,122,705 (GRCm39)	D53G	probably benign	Het
Nol8	T	C	13: 49,815,628 (GRCm39)	S561P	probably damaging	Het
Nuf2	A	C	1: 169,352,866 (GRCm39)		probably benign	Het
Odad3	T	A	9: 21,903,004 (GRCm39)	H442L	probably benign	Het
Ofcc1	T	A	13: 40,168,789 (GRCm39)	D866V	possibly damaging	Het
Optn	A	G	2: 5,051,006 (GRCm39)	L125P	probably benign	Het
Or5k3	A	G	16: 58,969,662 (GRCm39)	I150V	probably benign	Het
Otoa	T	A	7: 120,730,564 (GRCm39)	F588Y	probably benign	Het
Pappa	T	A	4: 65,269,850 (GRCm39)		probably null	Het
Pde5a	T	G	3: 122,629,232 (GRCm39)	C635W	probably damaging	Het
Pdgfb	A	T	15: 79,887,620 (GRCm39)		probably null	Het
Pih1d2	T	A	9: 50,532,346 (GRCm39)	C135S	probably damaging	Het
Plcg1	G	T	2: 160,594,286 (GRCm39)	C361F	probably damaging	Het
Ppp4r4	T	C	12: 103,567,619 (GRCm39)		probably benign	Het
Pramel26	T	A	4: 143,538,269 (GRCm39)	D234V	probably benign	Het
Prdm10	G	A	9: 31,260,564 (GRCm39)		probably null	Het
Prex2	T	A	1: 11,159,930 (GRCm39)		probably null	Het
Prss56	T	G	1: 87,112,452 (GRCm39)		probably null	Het
Prtg	A	G	9: 72,752,240 (GRCm39)	K209E	probably benign	Het
Ptprc	G	A	1: 138,050,313 (GRCm39)	T36I	possibly damaging	Het
Rasgrp4	A	G	7: 28,845,285 (GRCm39)	Y302C	probably damaging	Het
Rb1cc1	T	A	1: 6,318,858 (GRCm39)	M759K	probably damaging	Het
Rbm15b	T	A	9: 106,763,197 (GRCm39)	M324L	probably benign	Het
Rcbtb2	T	C	14: 73,415,987 (GRCm39)	V500A	probably damaging	Het
Rgs6	A	G	12: 83,180,451 (GRCm39)	K434R	probably damaging	Het
Rims1	C	T	1: 22,635,607 (GRCm39)	A125T	possibly damaging	Het
Robo3	A	G	9: 37,333,473 (GRCm39)	V746A	probably benign	Het
Rtl1	C	T	12: 109,557,820 (GRCm39)	E1340K	unknown	Het
Sacs	G	A	14: 61,443,089 (GRCm39)	D1712N	possibly damaging	Het
Samd4b	G	A	7: 28,103,402 (GRCm39)	P19S	probably benign	Het
Samhd1	T	C	2: 156,956,151 (GRCm39)	Y347C	probably damaging	Het
Sema6d	T	A	2: 124,500,410 (GRCm39)	I393N	probably damaging	Het
Sigmar1	C	T	4: 41,741,243 (GRCm39)	A4T	probably benign	Het
Skint9	C	A	4: 112,246,376 (GRCm39)	L245F	probably benign	Het
Slc35f5	T	C	1: 125,512,832 (GRCm39)	L372P	probably damaging	Het
Smc1b	A	T	15: 84,950,478 (GRCm39)	I1182N	probably damaging	Het
Smyd3	A	G	1: 178,785,138 (GRCm39)		probably benign	Het
Sptlc1	T	C	13: 53,491,648 (GRCm39)	D417G	probably benign	Het
Sv2c	T	C	13: 96,225,216 (GRCm39)	N31S	probably benign	Het
Tjp1	T	C	7: 64,964,738 (GRCm39)	D811G	probably damaging	Het
Top2b	A	G	14: 16,418,442 (GRCm38)	T1221A	probably benign	Het
Tph2	T	C	10: 115,010,014 (GRCm39)	D182G	probably damaging	Het
Traf6	C	T	2: 101,518,933 (GRCm39)	Q141*	probably null	Het
Ttn	T	C	2: 76,587,275 (GRCm39)	D21574G	probably damaging	Het
Uba2	T	A	7: 33,850,446 (GRCm39)	N367I	probably benign	Het
Ube2b	T	C	11: 51,879,429 (GRCm39)		probably benign	Het
Ubr5	G	T	15: 38,030,916 (GRCm39)	L426I	probably benign	Het
Ugt2a2	T	A	5: 87,612,007 (GRCm39)	H301L	probably benign	Het
Upf2	T	A	2: 6,023,705 (GRCm39)		probably benign	Het
Utrn	T	C	10: 12,585,804 (GRCm39)	D991G	probably benign	Het
Vmn2r25	T	C	6: 123,800,140 (GRCm39)	D734G	probably damaging	Het
Vmn2r68	C	G	7: 84,882,466 (GRCm39)		probably null	Het
Vmn2r68	T	A	7: 84,882,457 (GRCm39)		probably benign	Het
Vwf	T	A	6: 125,603,324 (GRCm39)	Y891*	probably null	Het
Wwox	C	T	8: 115,433,018 (GRCm39)	T228I	probably benign	Het
Zer1	C	T	2: 29,998,225 (GRCm39)		probably benign	Het
Zfp180	C	T	7: 23,804,132 (GRCm39)	H184Y	possibly damaging	Het
Zfp68	A	T	5: 138,605,487 (GRCm39)	Y279N	probably benign	Het

Other mutations in Cbl

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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

Predicted Primers

PCR Primer
(F):5'- TGCCTGCAACCTTTCTCAGGAGTG -3'
(R):5'- GCTCAAGAACAGCCCGCCTTATATC -3'

Sequencing Primer
(F):5'- GATGGTCAACTGCTTACCAAG -3'
(R):5'- ACAGCCCGCCTTATATCTTAGAC -3'

Posted On

2013-04-24