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, c-Cbl

MMRRC Submission

038596-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.668) question?

Stock #

R0390 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

44142976-44234049 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 44201005 bp (GRCm38)

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
A730017C20Rik	T	A	18: 59,075,688	V136E	probably damaging	Het
Adam18	C	T	8: 24,674,054	G38R	probably benign	Het
Ap2m1	T	C	16: 20,541,099	M183T	probably damaging	Het
Apob	A	T	12: 7,988,678	I364F	probably damaging	Het
Arl6	A	T	16: 59,622,421		probably benign	Het
Cand2	A	G	6: 115,774,653	M15V	possibly damaging	Het
Ccdc151	T	A	9: 21,991,708	H442L	probably benign	Het
Ccdc74a	A	G	16: 17,650,476	S321G	probably benign	Het
Cdc14b	T	C	13: 64,210,192		probably benign	Het
Cep152	T	C	2: 125,576,869		probably benign	Het
Cep290	A	G	10: 100,508,758	E479G	probably benign	Het
Chrm2	T	G	6: 36,524,111	I301R	probably benign	Het
Clec2e	A	G	6: 129,093,468	W197R	probably damaging	Het
Cnot10	G	T	9: 114,629,150	S96*	probably null	Het
Col19a1	A	G	1: 24,289,655		probably benign	Het
Csmd2	T	C	4: 128,133,673		probably benign	Het
Cthrc1	A	T	15: 39,086,764	*172L	probably null	Het
Cul9	A	T	17: 46,528,589	I821N	probably benign	Het
Daam1	G	C	12: 71,975,304		probably benign	Het
Dhx58	A	T	11: 100,699,264	I398N	probably damaging	Het
Dip2b	T	A	15: 100,193,913	H844Q	probably damaging	Het
Dmac2	A	G	7: 25,621,029	D50G	probably damaging	Het
Dmxl1	C	A	18: 49,879,362	Q1529K	probably benign	Het
Dtna	C	T	18: 23,597,501	P315L	probably damaging	Het
Ep300	T	C	15: 81,640,116	S1382P	unknown	Het
Fat2	A	T	11: 55,310,777	N490K	probably damaging	Het
Flg2	T	A	3: 93,200,355		probably benign	Het
Gm13084	T	A	4: 143,811,699	D234V	probably benign	Het
Gpatch1	T	C	7: 35,281,381		probably benign	Het
Grin2a	C	A	16: 9,579,585	K879N	possibly damaging	Het
Hacd3	A	C	9: 65,001,022	I164S	possibly damaging	Het
Hinfp	A	C	9: 44,298,948	C197G	probably damaging	Het
Hsd17b12	T	C	2: 94,114,990		probably benign	Het
Hsd3b1	A	T	3: 98,853,039	L212Q	probably damaging	Het
Ifrd1	C	T	12: 40,214,094		probably null	Het
Igf2bp2	A	G	16: 22,081,801	F129L	possibly damaging	Het
Kirrel3	T	A	9: 35,020,163	I409N	probably damaging	Het
Klhdc10	T	C	6: 30,447,412	I204T	probably damaging	Het
Kpna6	A	T	4: 129,657,804	S65R	possibly damaging	Het
Lama3	A	T	18: 12,407,563	D308V	probably benign	Het
Larp4b	T	A	13: 9,158,107		probably null	Het
Lgr6	C	T	1: 134,994,010	A199T	probably damaging	Het
Lyzl1	A	T	18: 4,169,175	T11S	probably benign	Het
Man1c1	A	G	4: 134,578,315	L366P	probably damaging	Het
Mef2a	A	G	7: 67,251,724	M100T	probably damaging	Het
Mettl13	G	A	1: 162,538,889	H474Y	possibly damaging	Het
Mmp3	A	G	9: 7,451,320	D352G	probably benign	Het
Mns1	T	C	9: 72,452,804	I412T	probably damaging	Het
Mon2	T	C	10: 123,007,021	D1501G	probably null	Het
Mylk	G	T	16: 34,875,620	G242W	probably damaging	Het
Nav1	T	C	1: 135,449,966	D1715G	possibly damaging	Het
Nckap1l	T	C	15: 103,453,883	S2P	probably damaging	Het
Nek3	A	T	8: 22,128,729		probably benign	Het
Nfrkb	A	G	9: 31,388,897		probably benign	Het
Nlrp4d	T	C	7: 10,388,778	D53G	probably benign	Het
Nol8	T	C	13: 49,662,152	S561P	probably damaging	Het
Nuf2	A	C	1: 169,525,297		probably benign	Het
Ofcc1	T	A	13: 40,015,313	D866V	possibly damaging	Het
Olfr195	A	G	16: 59,149,299	I150V	probably benign	Het
Optn	A	G	2: 5,046,195	L125P	probably benign	Het
Otoa	T	A	7: 121,131,341	F588Y	probably benign	Het
Pappa	T	A	4: 65,351,613		probably null	Het
Pde5a	T	G	3: 122,835,583	C635W	probably damaging	Het
Pdgfb	A	T	15: 80,003,419		probably null	Het
Pih1d2	T	A	9: 50,621,046	C135S	probably damaging	Het
Plcg1	G	T	2: 160,752,366	C361F	probably damaging	Het
Ppp4r4	T	C	12: 103,601,360		probably benign	Het
Prdm10	G	A	9: 31,349,268		probably null	Het
Prex2	T	A	1: 11,089,706		probably null	Het
Prss56	T	G	1: 87,184,730		probably null	Het
Prtg	A	G	9: 72,844,958	K209E	probably benign	Het
Ptprc	G	A	1: 138,122,575	T36I	possibly damaging	Het
Rasgrp4	A	G	7: 29,145,860	Y302C	probably damaging	Het
Rb1cc1	T	A	1: 6,248,634	M759K	probably damaging	Het
Rbm15b	T	A	9: 106,885,998	M324L	probably benign	Het
Rcbtb2	T	C	14: 73,178,547	V500A	probably damaging	Het
Rgs6	A	G	12: 83,133,677	K434R	probably damaging	Het
Rims1	C	T	1: 22,596,526	A125T	possibly damaging	Het
Robo3	A	G	9: 37,422,177	V746A	probably benign	Het
Rtl1	C	T	12: 109,591,386	E1340K	unknown	Het
Sacs	G	A	14: 61,205,640	D1712N	possibly damaging	Het
Samd4b	G	A	7: 28,403,977	P19S	probably benign	Het
Samhd1	T	C	2: 157,114,231	Y347C	probably damaging	Het
Sema6d	T	A	2: 124,658,490	I393N	probably damaging	Het
Sigmar1	C	T	4: 41,741,243	A4T	probably benign	Het
Skint9	C	A	4: 112,389,179	L245F	probably benign	Het
Slc35f5	T	C	1: 125,585,095	L372P	probably damaging	Het
Smc1b	A	T	15: 85,066,277	I1182N	probably damaging	Het
Smyd3	A	G	1: 178,957,573		probably benign	Het
Sptlc1	T	C	13: 53,337,612	D417G	probably benign	Het
Sv2c	T	C	13: 96,088,708	N31S	probably benign	Het
Tjp1	T	C	7: 65,314,990	D811G	probably damaging	Het
Top2b	A	G	14: 16,418,442	T1221A	probably benign	Het
Tph2	T	C	10: 115,174,109	D182G	probably damaging	Het
Traf6	C	T	2: 101,688,588	Q141*	probably null	Het
Ttn	T	C	2: 76,756,931	D21574G	probably damaging	Het
Uba2	T	A	7: 34,151,021	N367I	probably benign	Het
Ube2b	T	C	11: 51,988,602		probably benign	Het
Ubr5	G	T	15: 38,030,672	L426I	probably benign	Het
Ugt2a2	T	A	5: 87,464,148	H301L	probably benign	Het
Upf2	T	A	2: 6,018,894		probably benign	Het
Utrn	T	C	10: 12,710,060	D991G	probably benign	Het
Vmn2r25	T	C	6: 123,823,181	D734G	probably damaging	Het
Vmn2r68	T	A	7: 85,233,249		probably benign	Het
Vmn2r68	C	G	7: 85,233,258		probably null	Het
Vwf	T	A	6: 125,626,361	Y891*	probably null	Het
Wwox	C	T	8: 114,706,278	T228I	probably benign	Het
Zer1	C	T	2: 30,108,213		probably benign	Het
Zfp180	C	T	7: 24,104,707	H184Y	possibly damaging	Het
Zfp68	A	T	5: 138,607,225	Y279N	probably benign	Het

Other mutations in Cbl

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00590:Cbl	APN	9	44201198	missense	probably damaging	1.00
IGL01369:Cbl	APN	9	44201061	nonsense	probably null
IGL01434:Cbl	APN	9	44164206	missense	probably damaging	0.99
IGL01866:Cbl	APN	9	44153825	nonsense	probably null
IGL02326:Cbl	APN	9	44151473	missense	possibly damaging	0.94
IGL02956:Cbl	APN	9	44169034	missense	probably damaging	1.00
Bungalow	UTSW	9	44201119	missense	probably damaging	1.00
Casita	UTSW	9	44164165	missense	probably damaging	1.00
tiny_house	UTSW	9	44164152	missense	probably damaging	1.00
R0068:Cbl	UTSW	9	44154194	missense	probably damaging	0.98
R0655:Cbl	UTSW	9	44158752	missense	probably damaging	1.00
R0764:Cbl	UTSW	9	44164152	missense	probably damaging	1.00
R1466:Cbl	UTSW	9	44154244	missense	probably benign	0.10
R1466:Cbl	UTSW	9	44154244	missense	probably benign	0.10
R1616:Cbl	UTSW	9	44152900	missense	probably damaging	0.99
R1736:Cbl	UTSW	9	44152895	missense	possibly damaging	0.80
R1808:Cbl	UTSW	9	44164229	missense	probably damaging	1.00
R1865:Cbl	UTSW	9	44164165	missense	probably damaging	1.00
R3156:Cbl	UTSW	9	44158850	missense	possibly damaging	0.74
R3431:Cbl	UTSW	9	44151446	makesense	probably null
R4668:Cbl	UTSW	9	44153848	missense	probably benign	0.00
R4700:Cbl	UTSW	9	44173380	missense	probably damaging	1.00
R4866:Cbl	UTSW	9	44152869	missense	probably benign	0.00
R4900:Cbl	UTSW	9	44152869	missense	probably benign	0.00
R4995:Cbl	UTSW	9	44153811	missense	possibly damaging	0.62
R5014:Cbl	UTSW	9	44154399	splice site	probably null
R5324:Cbl	UTSW	9	44154254	missense	probably damaging	0.97
R5353:Cbl	UTSW	9	44173323	missense	probably damaging	1.00
R5382:Cbl	UTSW	9	44159021	missense	probably benign
R5747:Cbl	UTSW	9	44201119	missense	probably damaging	1.00
R5834:Cbl	UTSW	9	44233779	missense	probably damaging	1.00
R6307:Cbl	UTSW	9	44158512	critical splice donor site	probably null
R6755:Cbl	UTSW	9	44173374	missense	probably damaging	0.98
R7393:Cbl	UTSW	9	44154188	critical splice donor site	probably null
R7779:Cbl	UTSW	9	44159096	missense	probably benign
R7789:Cbl	UTSW	9	44163467	missense	probably damaging	1.00
R8094:Cbl	UTSW	9	44163399	missense	probably benign	0.03
R8104:Cbl	UTSW	9	44158539	missense	possibly damaging	0.93
R8146:Cbl	UTSW	9	44164874	missense	probably damaging	1.00
R8340:Cbl	UTSW	9	44159000	missense	possibly damaging	0.77
R8424:Cbl	UTSW	9	44152854	missense	possibly damaging	0.51
R8920:Cbl	UTSW	9	44167273	missense	probably damaging	0.99
R9185:Cbl	UTSW	9	44152840	missense	probably damaging	1.00
X0057:Cbl	UTSW	9	44233767	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