Mutagenetix > Incidental Mutation

Incidental Mutation 'R4995:Cbl'

385182

Institutional Source

Beutler Lab

Gene Symbol

Cbl

Ensembl Gene

ENSMUSG00000034342

Gene Name

Casitas B-lineage lymphoma

Synonyms

Cbl-2, 4732447J05Rik, c-Cbl

MMRRC Submission

042589-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.520) question?

Stock #

R4995 (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 44065108 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Threonine at position 740 (M740T)

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: M696T

PolyPhen 2 Score 0.342 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000041902
Gene: ENSMUSG00000034342
AA Change: M696T

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

noncoding transcript
Transcript: ENSMUST00000205313

Predicted Effect

probably benign
Transcript: ENSMUST00000205968
AA Change: M723T

PolyPhen 2 Score 0.336 (Sensitivity: 0.90; Specificity: 0.89)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000206125

Predicted Effect

possibly damaging
Transcript: ENSMUST00000206147
AA Change: M740T

PolyPhen 2 Score 0.485 (Sensitivity: 0.88; Specificity: 0.90)

Predicted Effect

unknown
Transcript: ENSMUST00000206258
AA Change: M39T

Predicted Effect

possibly damaging
Transcript: ENSMUST00000206720
AA Change: M740T

PolyPhen 2 Score 0.622 (Sensitivity: 0.87; Specificity: 0.91)

Meta Mutation Damage Score

0.1636

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 96.7%
20x: 93.6%

Validation Efficiency

99% (86/87)

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: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4921504E06Rik	G	A	2: 19,498,995 (GRCm39)	Q333*	probably null	Het
4930505A04Rik	C	T	11: 30,376,349 (GRCm39)	V173M	probably damaging	Het
Acvrl1	G	A	15: 101,033,741 (GRCm39)	R141H	probably benign	Het
Adprm	A	G	11: 66,932,436 (GRCm39)	F158L	possibly damaging	Het
Aldoart2	C	T	12: 55,613,038 (GRCm39)	T321M	probably benign	Het
Ap3m2	A	G	8: 23,293,792 (GRCm39)	V86A	probably benign	Het
Arhgef19	T	A	4: 140,974,826 (GRCm39)		probably null	Het
Bcl2l12	T	G	7: 44,643,615 (GRCm39)		probably null	Het
Bptf	T	C	11: 106,945,391 (GRCm39)	Q2501R	probably damaging	Het
C230029F24Rik	A	T	1: 49,377,295 (GRCm39)		noncoding transcript	Het
C7	C	T	15: 5,079,074 (GRCm39)	G78D	probably damaging	Het
Caly	T	C	7: 139,650,538 (GRCm39)	T135A	probably benign	Het
Cbx4	A	G	11: 118,972,037 (GRCm39)	V446A	probably benign	Het
Celsr1	C	A	15: 85,822,112 (GRCm39)	R1735L	probably damaging	Het
Cep250	A	G	2: 155,830,236 (GRCm39)	D135G	probably damaging	Het
Cgn	T	C	3: 94,687,246 (GRCm39)	T19A	probably damaging	Het
Chic2	A	T	5: 75,204,865 (GRCm39)	V32D	probably damaging	Het
Cntln	A	G	4: 84,968,120 (GRCm39)	K780E	probably benign	Het
Col8a2	A	T	4: 126,204,581 (GRCm39)	D197V	probably damaging	Het
Crot	A	T	5: 9,024,000 (GRCm39)	V372E	probably damaging	Het
Cyb561d2	C	T	9: 107,418,747 (GRCm39)	V26M	probably damaging	Het
Ddx5	G	A	11: 106,676,062 (GRCm39)	T237I	probably damaging	Het
Dmxl2	G	T	9: 54,408,725 (GRCm39)		probably benign	Het
Dock8	T	A	19: 25,135,747 (GRCm39)	S1188R	probably benign	Het
Ehbp1	T	A	11: 22,051,073 (GRCm39)	H493L	probably damaging	Het
Eif5b	T	A	1: 38,090,792 (GRCm39)	*1217K	probably null	Het
Eprs1	A	G	1: 185,142,336 (GRCm39)		probably benign	Het
Etfdh	T	C	3: 79,513,095 (GRCm39)	D376G	probably benign	Het
Fam186a	T	C	15: 99,842,980 (GRCm39)	Q1088R	probably benign	Het
Fbxw16	G	T	9: 109,270,318 (GRCm39)	T141N	probably damaging	Het
Fgf11	G	A	11: 69,689,585 (GRCm39)	H138Y	probably damaging	Het
Htra3	T	C	5: 35,828,418 (GRCm39)	E154G	probably damaging	Het
Hydin	T	A	8: 111,296,274 (GRCm39)	V3601D	probably damaging	Het
Jup	G	T	11: 100,270,367 (GRCm39)	S380*	probably null	Het
Klrg1	T	A	6: 122,255,234 (GRCm39)	D66V	probably benign	Het
Llgl1	C	T	11: 60,600,550 (GRCm39)	A633V	probably benign	Het
Lmln	T	A	16: 32,894,467 (GRCm39)	Y203*	probably null	Het
Lrrc58	T	G	16: 37,697,418 (GRCm39)	C165G	probably benign	Het
Lss	T	C	10: 76,383,371 (GRCm39)	V557A	probably benign	Het
Mast4	T	C	13: 103,042,262 (GRCm39)		probably benign	Het
Med13l	C	A	5: 118,869,014 (GRCm39)	P754Q	possibly damaging	Het
Mga	C	T	2: 119,763,063 (GRCm39)	R1240*	probably null	Het
Mgat5b	T	A	11: 116,865,025 (GRCm39)		probably null	Het
Mtor	A	G	4: 148,610,209 (GRCm39)	D1572G	probably damaging	Het
Muc4	T	A	16: 32,754,214 (GRCm38)	S1363T	probably benign	Het
Muc4	T	A	16: 32,575,332 (GRCm39)	S1306T	probably benign	Het
Myo18b	A	G	5: 112,908,258 (GRCm39)	V2005A	probably damaging	Het
Myo1e	G	A	9: 70,260,554 (GRCm39)	D571N	probably benign	Het
Mypn	T	C	10: 62,955,747 (GRCm39)		probably null	Het
Ndufb10	T	C	17: 24,941,731 (GRCm39)		probably null	Het
Nelfb	G	T	2: 25,096,208 (GRCm39)	D300E	probably benign	Het
Nicol1	G	A	5: 34,142,270 (GRCm39)	R79H	probably damaging	Het
Odad2	G	A	18: 7,223,663 (GRCm39)	T460M	probably damaging	Het
Or2y1d	T	A	11: 49,321,482 (GRCm39)	Y60N	probably damaging	Het
Or4e5	A	T	14: 52,727,988 (GRCm39)	C61*	probably null	Het
Or52n2c	T	A	7: 104,574,942 (GRCm39)	T10S	probably benign	Het
Or52z15	T	A	7: 103,332,574 (GRCm39)	D206E	probably damaging	Het
Pcdha11	C	T	18: 37,144,080 (GRCm39)	T57M	probably benign	Het
Pkp1	A	T	1: 135,808,593 (GRCm39)	I458N	possibly damaging	Het
Prr12	T	A	7: 44,700,653 (GRCm39)		probably benign	Het
Prrc2c	A	T	1: 162,532,879 (GRCm39)		probably benign	Het
Psd4	T	C	2: 24,287,259 (GRCm39)	F397S	probably benign	Het
Pygm	T	C	19: 6,448,169 (GRCm39)	I737T	probably damaging	Het
Rfx1	T	A	8: 84,806,743 (GRCm39)		probably null	Het
Rsl1	A	G	13: 67,330,313 (GRCm39)	T254A	possibly damaging	Het
Sh3rf3	A	G	10: 58,922,646 (GRCm39)	Q574R	probably benign	Het
Spire1	T	C	18: 67,685,849 (GRCm39)		probably null	Het
St6galnac4	G	A	2: 32,484,075 (GRCm39)	G91D	probably damaging	Het
Sytl2	T	C	7: 90,031,465 (GRCm39)		probably benign	Het
Tbpl2	T	A	2: 23,983,872 (GRCm39)	K188N	possibly damaging	Het
Tenm3	A	T	8: 48,682,172 (GRCm39)	M2486K	possibly damaging	Het
Tgoln1	A	C	6: 72,593,123 (GRCm39)	V119G	possibly damaging	Het
Tpgs1	A	T	10: 79,505,325 (GRCm39)	N28Y	probably benign	Het
U2surp	A	C	9: 95,344,847 (GRCm39)		probably benign	Het
Vmn2r103	A	G	17: 19,993,773 (GRCm39)	H50R	probably benign	Het
Vmn2r19	A	G	6: 123,306,869 (GRCm39)	N459S	probably benign	Het
Vmn2r72	T	C	7: 85,387,693 (GRCm39)	S624G	probably damaging	Het
Vps13c	A	G	9: 67,826,603 (GRCm39)	T1415A	probably benign	Het
Vwa5b1	G	A	4: 138,336,154 (GRCm39)	P147S	probably damaging	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
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
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'- AAGTGGGTCCATCTTGTCCAC -3'
(R):5'- GGCCTCTAGAACATGCACATC -3'

Sequencing Primer
(F):5'- CCAGACAGGGTATTTGCTATGCAG -3'
(R):5'- GCACATCTGATCTTGTCATGAGTCAG -3'

Posted On

2016-05-10