Mutagenetix > Incidental Mutation

Incidental Mutation 'R4776:Fbxw7'

367900

Institutional Source

Beutler Lab

Gene Symbol

Fbxw7

Ensembl Gene

ENSMUSG00000028086

Gene Name

F-box and WD-40 domain protein 7

Synonyms

Fbw7, 1110001A17Rik, AGO, Cdc4, Fbxw6, SEL-10, Fbxo30

MMRRC Submission

042413-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4776 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

84815268-84979198 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to G at 84925689 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Valine at position 13 (L13V)

Ref Sequence

ENSEMBL: ENSMUSP00000103302 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000107675] [ENSMUST00000107678] [ENSMUST00000107679] [ENSMUST00000154148]

AlphaFold

Q8VBV4

Predicted Effect

possibly damaging
Transcript: ENSMUST00000107675
AA Change: L13V

PolyPhen 2 Score 0.528 (Sensitivity: 0.88; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000103302
Gene: ENSMUSG00000028086
AA Change: L13V

Domain	Start	End	E-Value	Type
low complexity region	99	106	N/A	INTRINSIC
FBOX	166	206	3.7e-8	SMART
WD40	251	289	3.14e-6	SMART
WD40	292	329	2.1e-7	SMART
WD40	332	369	7.55e-9	SMART
WD40	372	409	2.22e-6	SMART
WD40	412	449	1.07e-8	SMART
WD40	452	489	1.75e-4	SMART
WD40	492	532	2.32e-9	SMART
WD40	535	583	2.37e2	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000107678

SMART Domains

Protein: ENSMUSP00000103305
Gene: ENSMUSG00000028086

Domain	Start	End	E-Value	Type
coiled coil region	94	129	N/A	INTRINSIC
low complexity region	220	227	N/A	INTRINSIC
FBOX	287	327	3.7e-8	SMART
WD40	372	410	3.14e-6	SMART
WD40	413	450	2.1e-7	SMART
WD40	453	490	7.55e-9	SMART
WD40	493	530	2.22e-6	SMART
WD40	533	570	1.07e-8	SMART
WD40	573	610	1.75e-4	SMART
WD40	613	653	2.32e-9	SMART
WD40	656	704	2.37e2	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000107679

SMART Domains

Protein: ENSMUSP00000103306
Gene: ENSMUSG00000028086

Domain	Start	End	E-Value	Type
coiled coil region	94	129	N/A	INTRINSIC
low complexity region	220	227	N/A	INTRINSIC
FBOX	287	327	3.7e-8	SMART
WD40	372	410	3.14e-6	SMART
WD40	413	450	2.1e-7	SMART
WD40	453	490	7.55e-9	SMART
WD40	493	530	2.22e-6	SMART
WD40	533	570	1.07e-8	SMART
WD40	573	610	1.75e-4	SMART
WD40	613	653	2.32e-9	SMART
WD40	656	704	2.37e2	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000151410

Predicted Effect

probably benign
Transcript: ENSMUST00000154148

SMART Domains

Protein: ENSMUSP00000116393
Gene: ENSMUSG00000102805

Domain	Start	End	E-Value	Type
Arfaptin	1	227	7.15e-121	SMART

Meta Mutation Damage Score

0.0814

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 96.8%
20x: 93.9%

Validation Efficiency

98% (94/96)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene was previously referred to as FBX30, and belongs to the Fbws class; in addition to an F-box, this protein contains 7 tandem WD40 repeats. This protein binds directly to cyclin E and probably targets cyclin E for ubiquitin-mediated degradation. Mutations in this gene are detected in ovarian and breast cancer cell lines, implicating the gene's potential role in the pathogenesis of human cancers. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]
PHENOTYPE: Homozygous inactivation of this locus disrupts embryonic and extraembryonic vasculature, resulting in death by midgestation. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 90 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310035C23Rik	T	A	1: 105,719,535	Y683*	probably null	Het
2610028H24Rik	A	T	10: 76,457,512	M156L	probably benign	Het
4930470P17Rik	C	T	2: 170,579,724	A79T	unknown	Het
4930522L14Rik	A	G	5: 109,736,873	I373T	probably benign	Het
A830010M20Rik	C	A	5: 107,510,451	A1117E	probably damaging	Het
Amotl1	G	A	9: 14,593,373	Q217*	probably null	Het
Ankrd28	A	T	14: 31,732,054	C254S	probably damaging	Het
Ap2a1	A	G	7: 44,901,546		probably benign	Het
Arfgef3	A	T	10: 18,654,247	S245T	probably benign	Het
Arntl	A	T	7: 113,285,037	K94I	probably damaging	Het
Atp1b2	A	T	11: 69,601,561	D224E	probably damaging	Het
Boc	G	A	16: 44,487,721	R924W	probably damaging	Het
Car14	C	T	3: 95,898,873	G292D	probably benign	Het
Cenpb	T	C	2: 131,178,183		probably benign	Het
Ces1b	A	T	8: 93,063,030	D423E	possibly damaging	Het
Cfap54	T	A	10: 92,972,694	N1373I	possibly damaging	Het
Chrdl2	T	C	7: 100,006,541		probably benign	Het
Cic	T	G	7: 25,282,883	S12A	possibly damaging	Het
Csmd2	A	T	4: 128,442,892	Q1421L	probably benign	Het
D630039A03Rik	T	C	4: 57,910,452	H120R	possibly damaging	Het
Dicer1	T	A	12: 104,692,446	D1779V	probably damaging	Het
Dock9	G	T	14: 121,610,097	H1016N	possibly damaging	Het
Dxo	T	C	17: 34,838,998	L352P	probably damaging	Het
Eif2b5	T	A	16: 20,500,233	F78I	probably damaging	Het
Eri2	A	G	7: 119,784,946		probably benign	Het
Fam208b	A	G	13: 3,570,391	F2170S	probably damaging	Het
Fgf7	T	A	2: 126,035,783	C23*	probably null	Het
Fubp1	T	A	3: 152,222,068		probably null	Het
Gm2663	A	T	6: 40,995,953	I240N	probably damaging	Het
Gnb1l	C	T	16: 18,548,096	Q140*	probably null	Het
Gnptab	G	A	10: 88,436,528	R1010Q	probably damaging	Het
Gtf2h1	G	A	7: 46,822,878	W544*	probably null	Het
Gucy2c	C	T	6: 136,722,514	E586K	probably damaging	Het
Hc	T	A	2: 35,039,734	E232V	probably benign	Het
Ifi207	T	A	1: 173,730,056	D372V	unknown	Het
Igkv8-28	A	T	6: 70,144,118	V15E	probably benign	Het
Il1rap	A	G	16: 26,692,799	S198G	possibly damaging	Het
Lct	A	G	1: 128,300,387	I1123T	probably damaging	Het
Lhcgr	T	C	17: 88,742,697	E467G	probably damaging	Het
Macf1	C	T	4: 123,476,015	R86K	probably benign	Het
Maml3	T	A	3: 51,856,532	Q337L	probably benign	Het
March10	T	A	11: 105,390,037	D474V	probably benign	Het
March2	G	T	17: 33,709,916	T2K	probably damaging	Het
Mast1	A	G	8: 84,937,193		probably null	Het
Med12l	T	C	3: 59,233,212	I868T	probably damaging	Het
Msrb1	T	C	17: 24,740,173	S100P	probably damaging	Het
Nlrp4c	T	C	7: 6,066,126	L342P	probably benign	Het
Nrxn3	T	A	12: 90,331,956	V417E	possibly damaging	Het
Ntng1	T	A	3: 109,934,713	D248V	probably damaging	Het
Oaz3	T	C	3: 94,434,998	Q117R	probably benign	Het
Olfr1311	A	G	2: 112,020,931	Y308H	probably benign	Het
Olfr444	A	G	6: 42,955,521	I8V	probably benign	Het
Olfr589	A	G	7: 103,155,414	L111P	probably benign	Het
Osbpl3	A	C	6: 50,300,973	S767A	probably benign	Het
Pafah1b1	A	T	11: 74,685,871		probably benign	Het
Pard6b	A	G	2: 168,098,788	T232A	probably damaging	Het
Paxip1	A	T	5: 27,765,206	C596S	probably damaging	Het
Pnpla6	T	C	8: 3,523,818	V422A	probably benign	Het
Psmd6	A	T	14: 14,120,932		probably benign	Het
Rock2	T	A	12: 16,977,740	C1353S	probably damaging	Het
Rpl31-ps17	C	T	12: 54,701,612		noncoding transcript	Het
Sel1l	T	A	12: 91,813,893	H658L	probably damaging	Het
Sh3yl1	T	A	12: 30,940,314	L105Q	probably damaging	Het
Shroom3	G	T	5: 92,943,086	V1151F	probably damaging	Het
Sirt1	T	C	10: 63,335,722	K227E	probably benign	Het
Slc25a34	A	T	4: 141,623,588	F37I	possibly damaging	Het
Slc39a5	T	A	10: 128,397,049	I378F	probably damaging	Het
Smarcad1	A	T	6: 65,098,824	D731V	probably null	Het
Sox6	T	G	7: 115,541,670	K483N	probably damaging	Het
Sp140	T	A	1: 85,610,828	D95E	possibly damaging	Het
Srgap1	G	T	10: 121,792,351	D882E	probably benign	Het
Syne4	T	C	7: 30,316,833		probably benign	Het
Tec	T	C	5: 72,768,776	Y289C	probably benign	Het
Tmem102	A	T	11: 69,804,802	Y115N	probably damaging	Het
Tns2	C	T	15: 102,108,934	R281C	probably damaging	Het
Trav17	T	A	14: 53,806,640	M1K	probably null	Het
Trdn	T	A	10: 33,399,082		probably null	Het
Trp53	A	T	11: 69,586,921	I8F	probably benign	Het
Ttn	T	A	2: 76,754,662	D22064V	probably damaging	Het
Ube3c	G	A	5: 29,632,838		probably null	Het
Ulk1	C	T	5: 110,788,947		probably null	Het
Upp1	T	C	11: 9,135,976	V271A	probably damaging	Het
Vmn2r4	T	C	3: 64,388,661	E901G	probably damaging	Het
Vmn2r96	G	A	17: 18,597,508	G449D	probably damaging	Het
Vps37b	T	C	5: 124,006,612	K165E	probably damaging	Het
Vwf	A	T	6: 125,566,305	I185F	possibly damaging	Het
Wasf2	A	G	4: 133,185,004	T56A	probably benign	Het
Zdhhc23	C	G	16: 43,973,589	D241H	possibly damaging	Het
Zfp276	T	C	8: 123,254,884	S57P	probably benign	Het
Zxdc	A	G	6: 90,370,518	H287R	probably damaging	Het

Other mutations in Fbxw7

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00719:Fbxw7	APN	3	84969309	intron	probably benign
IGL01468:Fbxw7	APN	3	84972499	missense	probably benign	0.21
IGL01946:Fbxw7	APN	3	84904062	missense	possibly damaging	0.60
IGL02248:Fbxw7	APN	3	84903633	missense	possibly damaging	0.94
IGL02630:Fbxw7	APN	3	84965279	missense	probably damaging	1.00
IGL02957:Fbxw7	APN	3	84976237	missense	probably benign	0.00
PIT4453001:Fbxw7	UTSW	3	84965314	missense
R0043:Fbxw7	UTSW	3	84972567	intron	probably benign
R0312:Fbxw7	UTSW	3	84967569	intron	probably benign
R0595:Fbxw7	UTSW	3	84977367	splice site	probably null
R1664:Fbxw7	UTSW	3	84969171	missense	possibly damaging	0.45
R1709:Fbxw7	UTSW	3	84976352	missense	probably damaging	1.00
R1782:Fbxw7	UTSW	3	84903819	missense	probably benign
R1974:Fbxw7	UTSW	3	84954935	missense	possibly damaging	0.53
R2081:Fbxw7	UTSW	3	84974513	missense	probably damaging	1.00
R2843:Fbxw7	UTSW	3	84976220	missense	probably damaging	1.00
R3732:Fbxw7	UTSW	3	84925707	missense	possibly damaging	0.72
R3732:Fbxw7	UTSW	3	84925707	missense	possibly damaging	0.72
R3733:Fbxw7	UTSW	3	84925707	missense	possibly damaging	0.72
R4333:Fbxw7	UTSW	3	84972495	missense	probably damaging	1.00
R4335:Fbxw7	UTSW	3	84972495	missense	probably damaging	1.00
R4581:Fbxw7	UTSW	3	84967545	missense	probably benign	0.41
R4799:Fbxw7	UTSW	3	84903861	nonsense	probably null
R4822:Fbxw7	UTSW	3	84967507	missense	possibly damaging	0.94
R5512:Fbxw7	UTSW	3	84954909	missense	probably damaging	0.99
R5601:Fbxw7	UTSW	3	84976208	missense	probably damaging	1.00
R5679:Fbxw7	UTSW	3	84977487	missense	probably damaging	1.00
R6026:Fbxw7	UTSW	3	84952641	critical splice donor site	probably null
R6182:Fbxw7	UTSW	3	84815771	critical splice donor site	probably null
R6219:Fbxw7	UTSW	3	84969213	missense	probably damaging	0.99
R6305:Fbxw7	UTSW	3	84976323	missense	probably damaging	1.00
R6473:Fbxw7	UTSW	3	84952380	intron	probably benign
R6823:Fbxw7	UTSW	3	84958627	missense	probably benign	0.33
R6922:Fbxw7	UTSW	3	84972416	splice site	probably null
R7163:Fbxw7	UTSW	3	84925585	intron	probably benign
R7229:Fbxw7	UTSW	3	84977369	missense	unknown
R7554:Fbxw7	UTSW	3	84976313	missense
R7677:Fbxw7	UTSW	3	84904066	missense
R7711:Fbxw7	UTSW	3	84925681	missense	probably benign
R7713:Fbxw7	UTSW	3	84967565	critical splice donor site	probably null
R7873:Fbxw7	UTSW	3	84925764	missense	possibly damaging	0.53
R8319:Fbxw7	UTSW	3	84974552	missense
R8712:Fbxw7	UTSW	3	84952377	missense	unknown
R8802:Fbxw7	UTSW	3	84952386	missense	unknown
R8805:Fbxw7	UTSW	3	84954920	missense
R8887:Fbxw7	UTSW	3	84969242	missense
R8905:Fbxw7	UTSW	3	84965327	missense	possibly damaging	0.89
R9358:Fbxw7	UTSW	3	84976254	missense

Predicted Primers

PCR Primer
(F):5'- AGGTCAGGACACTCGCAAAG -3'
(R):5'- CGTTAGCTCTCCTCACAGAC -3'

Sequencing Primer
(F):5'- TCGCAAAGAGAAGGTTGGAAGAC -3'
(R):5'- CACACAGGCGATCGGAAGC -3'

Posted On

2015-12-29