Mutagenetix > Incidental Mutation

Incidental Mutation 'R7789:Cbl'

599749

Institutional Source

Beutler Lab

Gene Symbol

Cbl

Ensembl Gene

ENSMUSG00000034342

Gene Name

Casitas B-lineage lymphoma

Synonyms

Cbl-2, 4732447J05Rik, c-Cbl

MMRRC Submission

045845-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.520) question?

Stock #

R7789 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

44054273-44145346 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 44074764 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Asparagine at position 433 (D433N)

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: D433N

PolyPhen 2 Score 0.041 (Sensitivity: 0.94; Specificity: 0.83)

SMART Domains

Protein: ENSMUSP00000041902
Gene: ENSMUSG00000034342
AA Change: D433N

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 benign
Transcript: ENSMUST00000205968
AA Change: D416N

PolyPhen 2 Score 0.337 (Sensitivity: 0.90; Specificity: 0.89)

Predicted Effect

probably benign
Transcript: ENSMUST00000206147
AA Change: D433N

PolyPhen 2 Score 0.020 (Sensitivity: 0.95; Specificity: 0.80)

Predicted Effect

probably damaging
Transcript: ENSMUST00000206720
AA Change: D433N

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.5%

Validation Efficiency

99% (77/78)

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: 76 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930562C15Rik	G	A	16: 4,682,175 (GRCm39)	E163K	probably benign	Het
Adam34	T	A	8: 44,105,488 (GRCm39)	R52S	probably benign	Het
Adcy8	A	T	15: 64,743,623 (GRCm39)	C328*	probably null	Het
Ankrd26	G	T	6: 118,504,760 (GRCm39)	S716R	possibly damaging	Het
Ankrd26	G	T	6: 118,504,759 (GRCm39)	H717N	probably damaging	Het
Ankrd40	C	A	11: 94,225,535 (GRCm39)	P189T	probably damaging	Het
Anln	A	G	9: 22,263,333 (GRCm39)	S113P		Het
Arid5b	C	T	10: 67,934,417 (GRCm39)	G495E	probably benign	Het
Asxl1	C	T	2: 153,241,943 (GRCm39)	T832I	probably benign	Het
Bicd2	C	T	13: 49,533,135 (GRCm39)	R574C	probably damaging	Het
Boll	T	C	1: 55,399,826 (GRCm39)		probably null	Het
Casr	A	G	16: 36,315,653 (GRCm39)	F806L	probably damaging	Het
Casz1	C	A	4: 149,013,863 (GRCm39)	N142K	probably benign	Het
Ceacam14	T	A	7: 17,548,096 (GRCm39)	V62D	probably damaging	Het
Chst10	T	C	1: 38,923,532 (GRCm39)	N18S	probably benign	Het
Cyp2j6	C	T	4: 96,433,953 (GRCm39)	R119H	probably benign	Het
Cyp4a14	C	G	4: 115,352,107 (GRCm39)	V102L	probably benign	Het
Dnajb3	A	T	1: 88,133,399 (GRCm39)	M1K	probably null	Het
Dnajc6	A	T	4: 101,475,729 (GRCm39)	K534M	possibly damaging	Het
Dnase2a	T	C	8: 85,635,505 (GRCm39)		probably null	Het
Dock10	A	G	1: 80,536,930 (GRCm39)	I985T	possibly damaging	Het
Emsy	G	T	7: 98,270,696 (GRCm39)	P436Q	probably damaging	Het
Enpp1	A	T	10: 24,529,981 (GRCm39)		probably null	Het
Erc1	T	A	6: 119,750,670 (GRCm39)	R353*	probably null	Het
Fbn2	T	A	18: 58,172,385 (GRCm39)	D2140V	probably benign	Het
Fgfr1	T	A	8: 26,052,329 (GRCm39)	Y218*	probably null	Het
Fhod1	C	T	8: 106,056,740 (GRCm39)	R1045H	probably damaging	Het
Focad	G	T	4: 88,147,643 (GRCm39)	L427F	unknown	Het
Gbf1	T	A	19: 46,242,441 (GRCm39)	L144M	probably damaging	Het
Glmn	T	G	5: 107,696,941 (GRCm39)	N592T	probably benign	Het
Golgb1	C	G	16: 36,695,761 (GRCm39)	P87A	unknown	Het
H2bw2	G	A	X: 135,828,471 (GRCm39)	R120K	unknown	Het
Insyn2b	T	A	11: 34,352,537 (GRCm39)	M193K	probably benign	Het
Itga9	T	G	9: 118,487,564 (GRCm39)	F216V	possibly damaging	Het
Klhl18	T	C	9: 110,268,076 (GRCm39)	D149G	unknown	Het
Lcat	C	T	8: 106,668,857 (GRCm39)	V114M	probably benign	Het
Lrrc8c	C	A	5: 105,755,066 (GRCm39)	N280K	probably damaging	Het
Mettl8	T	C	2: 70,796,806 (GRCm39)	Y283C	probably damaging	Het
Mgat4a	A	T	1: 37,529,360 (GRCm39)	I173K	probably damaging	Het
Mmp1a	T	C	9: 7,475,266 (GRCm39)	V345A	possibly damaging	Het
Mok	T	A	12: 110,778,261 (GRCm39)	H215L	probably damaging	Het
Mphosph9	C	G	5: 124,453,650 (GRCm39)	E221Q	probably damaging	Het
Muc4	C	G	16: 32,575,221 (GRCm39)	Q1269E	probably benign	Het
Mug1	C	A	6: 121,838,179 (GRCm39)	H470N	possibly damaging	Het
Myom1	A	G	17: 71,424,431 (GRCm39)	T1525A	probably benign	Het
Nap1l1	C	T	10: 111,326,317 (GRCm39)	S143L	probably benign	Het
Or1af1	C	T	2: 37,109,672 (GRCm39)	T57I	probably benign	Het
Or2j6	A	T	7: 139,980,610 (GRCm39)	Y116*	probably null	Het
Or52d1	T	A	7: 103,756,195 (GRCm39)	S236R	probably damaging	Het
Or7g29	G	T	9: 19,286,361 (GRCm39)	T272K	probably benign	Het
Plbd2	T	C	5: 120,623,819 (GRCm39)	S568G	probably damaging	Het
Plxna4	T	A	6: 32,183,168 (GRCm39)		probably null	Het
Plxnc1	T	A	10: 94,630,339 (GRCm39)	E1520V	probably damaging	Het
Ppil3	G	A	1: 58,473,538 (GRCm39)	T104I	possibly damaging	Het
Ptprm	A	T	17: 67,402,534 (GRCm39)	V118E	probably damaging	Het
Rimbp2	T	C	5: 128,851,399 (GRCm39)	D849G	probably damaging	Het
Rnf213	T	C	11: 119,361,045 (GRCm39)		probably null	Het
Sema3f	T	A	9: 107,582,631 (GRCm39)	K37N	probably benign	Het
Sh3glb1	G	T	3: 144,397,892 (GRCm39)		probably null	Het
Sh3rf3	A	G	10: 58,922,637 (GRCm39)	D571G	probably benign	Het
Sipa1l3	T	C	7: 29,077,150 (GRCm39)	Y874C	probably damaging	Het
Smchd1	G	A	17: 71,782,296 (GRCm39)		probably benign	Het
Snrnp70	A	T	7: 45,026,045 (GRCm39)	Y441*	probably null	Het
Ssrp1	C	T	2: 84,871,525 (GRCm39)	R316W	probably damaging	Het
Syt10	A	T	15: 89,711,101 (GRCm39)	V144E	probably damaging	Het
Tdrd12	A	G	7: 35,188,117 (GRCm39)	L562P		Het
Trim68	T	C	7: 102,333,676 (GRCm39)	D2G	possibly damaging	Het
Trub2	T	A	2: 29,667,920 (GRCm39)	H240L	probably damaging	Het
Tssc4	A	G	7: 142,623,515 (GRCm39)		probably null	Het
Usp7	T	A	16: 8,516,675 (GRCm39)	Q539L	probably benign	Het
Vmn2r17	T	A	5: 109,600,831 (GRCm39)	C710S	possibly damaging	Het
Vmn2r99	G	T	17: 19,614,079 (GRCm39)	V600F	possibly damaging	Het
Vps13d	C	T	4: 144,826,635 (GRCm39)	V2879M		Het
Vrtn	T	A	12: 84,697,080 (GRCm39)	M610K	probably benign	Het
Xpo4	T	C	14: 57,850,806 (GRCm39)	E366G	probably benign	Het
Zyg11a	G	A	4: 108,040,845 (GRCm39)	P703S	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
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
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'- GCTTTCCGTCAATGTTTTATCACAG -3'
(R):5'- CTCTGAGCTATATCCTCATCAACTG -3'

Sequencing Primer
(F):5'- TAGAAATGCTGAACAAGACATCACTC -3'
(R):5'- CTGTACTTTAACCTCTGGAAACTG -3'

Posted On

2019-11-26