Mutagenetix > Incidental Mutation

Incidental Mutation 'R4866:Cbl'

374920

Institutional Source

Beutler Lab

Gene Symbol

Cbl

Ensembl Gene

ENSMUSG00000034342

Gene Name

Casitas B-lineage lymphoma

Synonyms

Cbl-2, 4732447J05Rik, c-Cbl

MMRRC Submission

042476-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.520) question?

Stock #

R4866 (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 44064166 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 790 (V790A)

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: V746A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000041902
Gene: ENSMUSG00000034342
AA Change: V746A

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: V773A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000206125

Predicted Effect

probably benign
Transcript: ENSMUST00000206147
AA Change: V790A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

Predicted Effect

probably benign
Transcript: ENSMUST00000206258

Predicted Effect

probably benign
Transcript: ENSMUST00000206720
AA Change: V790A

PolyPhen 2 Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)

Meta Mutation Damage Score

0.0660

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 96.9%
20x: 94.0%

Validation Efficiency

99% (79/80)

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: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca3	C	T	17: 24,593,274 (GRCm39)	R224C	probably damaging	Het
Abcc5	A	T	16: 20,241,182 (GRCm39)	M1K	probably null	Het
Ablim2	C	T	5: 35,959,766 (GRCm39)	R73C	possibly damaging	Het
Adam5	A	C	8: 25,232,172 (GRCm39)		probably null	Het
Adam5	G	A	8: 25,271,619 (GRCm39)	T596I	probably damaging	Het
Apoa2	T	C	1: 171,053,369 (GRCm39)		probably null	Het
Atad1	A	T	19: 32,679,964 (GRCm39)	H79Q	probably benign	Het
Atp8a2	T	C	14: 59,928,916 (GRCm39)	D1046G	probably damaging	Het
Bcam	A	G	7: 19,499,397 (GRCm39)	Y209H	probably benign	Het
Brpf1	G	A	6: 113,299,431 (GRCm39)	V1120I	probably damaging	Het
Catsperb	G	A	12: 101,474,208 (GRCm39)	C302Y	probably damaging	Het
Ccdc60	T	C	5: 116,310,549 (GRCm39)	D171G	probably damaging	Het
Cd300c2	A	T	11: 114,891,807 (GRCm39)	C22*	probably null	Het
Cdan1	C	A	2: 120,561,928 (GRCm39)		probably benign	Het
Cdk5rap1	C	T	2: 154,212,876 (GRCm39)		probably null	Het
Cfap410	T	A	10: 77,817,413 (GRCm39)		probably null	Het
Cfap65	T	C	1: 74,964,716 (GRCm39)	D479G	probably damaging	Het
Cmbl	A	G	15: 31,585,490 (GRCm39)	K113E	probably benign	Het
Cog6	G	A	3: 52,918,019 (GRCm39)	T173I	probably benign	Het
Cts6	T	A	13: 61,350,090 (GRCm39)		probably null	Het
Cyp11a1	G	A	9: 57,933,380 (GRCm39)	V413M	probably damaging	Het
Cyp2c39	G	A	19: 39,502,020 (GRCm39)	M136I	probably benign	Het
Dclre1b	A	T	3: 103,715,412 (GRCm39)	Y29N	probably damaging	Het
Depdc1a	T	A	3: 159,221,764 (GRCm39)	I236K	probably damaging	Het
Dhx36	A	T	3: 62,380,198 (GRCm39)	Y833N	probably damaging	Het
Dop1b	G	T	16: 93,560,318 (GRCm39)		probably null	Het
Elovl3	A	G	19: 46,120,603 (GRCm39)	E32G	possibly damaging	Het
Entrep1	A	G	19: 23,952,790 (GRCm39)	S507P	possibly damaging	Het
Epcam	T	C	17: 87,951,049 (GRCm39)	V212A	possibly damaging	Het
Fcrl2	A	T	3: 87,170,773 (GRCm39)	C4S	possibly damaging	Het
Galnt16	T	C	12: 80,630,851 (GRCm39)	Y310H	probably damaging	Het
Gm12789	G	A	4: 101,846,182 (GRCm39)		probably benign	Het
Gspt1	C	T	16: 11,040,529 (GRCm39)	R593H	possibly damaging	Het
Hmcn2	A	T	2: 31,279,403 (GRCm39)	T1802S	possibly damaging	Het
Igha	A	G	12: 113,223,129 (GRCm39)	V166A	probably benign	Het
Itfg2	A	G	6: 128,393,279 (GRCm39)		probably benign	Het
Jund	T	C	8: 71,152,254 (GRCm39)	V183A	probably damaging	Het
Katnb1	T	C	8: 95,824,132 (GRCm39)	S471P	possibly damaging	Het
Kazn	A	G	4: 141,832,216 (GRCm39)	F661S	unknown	Het
Kif19a	G	A	11: 114,658,053 (GRCm39)	M37I	probably benign	Het
Lgr5	C	T	10: 115,288,590 (GRCm39)	V661I	probably benign	Het
Lvrn	G	T	18: 47,026,768 (GRCm39)	A789S	probably damaging	Het
Mapk10	T	C	5: 103,111,391 (GRCm39)	D351G	probably damaging	Het
Mga	T	A	2: 119,794,535 (GRCm39)	C2622S	possibly damaging	Het
Mios	T	G	6: 8,214,857 (GRCm39)	F18V	probably damaging	Het
Mllt6	A	G	11: 97,565,285 (GRCm39)	D575G	probably damaging	Het
Mmp10	G	A	9: 7,508,190 (GRCm39)	V439M	probably damaging	Het
Myh4	A	G	11: 67,139,453 (GRCm39)	D590G	probably benign	Het
Ndufs2	C	T	1: 171,074,618 (GRCm39)	G14R	probably benign	Het
Or10ad1b	T	A	15: 98,125,371 (GRCm39)	I52F	probably damaging	Het
Or51a7	A	T	7: 102,614,927 (GRCm39)	M207L	probably benign	Het
Or56a4	T	C	7: 104,806,514 (GRCm39)	Y125C	possibly damaging	Het
Or8g26	A	G	9: 39,096,367 (GRCm39)	K298E	probably damaging	Het
Plau	G	T	14: 20,887,872 (GRCm39)	V39L	probably benign	Het
Ppp3cb	A	G	14: 20,573,911 (GRCm39)	C275R	probably damaging	Het
Ppp4r4	T	G	12: 103,566,706 (GRCm39)	M51R	possibly damaging	Het
Prr5	A	G	15: 84,626,105 (GRCm39)	Y60C	probably damaging	Het
Ptprt	T	C	2: 161,402,159 (GRCm39)	D1023G	probably damaging	Het
Raly	T	A	2: 154,703,816 (GRCm39)	V129E	probably damaging	Het
Rsph10b	A	G	5: 143,885,347 (GRCm39)	E249G	probably benign	Het
Sart1	A	C	19: 5,432,248 (GRCm39)	L577W	probably damaging	Het
Senp1	T	C	15: 97,964,729 (GRCm39)	E189G	possibly damaging	Het
Slc22a2	G	T	17: 12,803,316 (GRCm39)	C50F	probably damaging	Het
Spem1	A	T	11: 69,711,755 (GRCm39)	V303E	probably damaging	Het
Tgfb3	A	G	12: 86,124,588 (GRCm39)	V40A	possibly damaging	Het
Ttl	T	C	2: 128,923,147 (GRCm39)	S163P	probably damaging	Het
Ttll9	C	A	2: 152,844,920 (GRCm39)	N429K	probably benign	Het
Uggt1	G	A	1: 36,241,936 (GRCm39)	R333*	probably null	Het
Zfhx2	A	G	14: 55,302,993 (GRCm39)	S1664P	possibly damaging	Het
Zfp51	T	A	17: 21,682,012 (GRCm39)	D70E	possibly damaging	Het
Zfp592	T	A	7: 80,691,607 (GRCm39)	V1262E	probably damaging	Het
Zfp595	C	A	13: 67,465,760 (GRCm39)	G168C	probably damaging	Het
Zswim9	A	T	7: 12,995,095 (GRCm39)	S354T	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
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'- CCTAGGACCAGCTTTCCAAC -3'
(R):5'- TGGCTGCCTCTGGATTGAAG -3'

Sequencing Primer
(F):5'- CTACTCACTGACTTATTGACACGAG -3'
(R):5'- CCTCTGGATTGAAGTGTGTTGGAAAG -3'

Posted On

2016-03-17