Mutagenetix > Incidental Mutations

Incidental Mutation 'R4822:Fbxw7'

371192

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

042438-MU

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R4822 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

84815268-84979198 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 84967507 bp

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Phenylalanine at position 232 (Y232F)

Ref Sequence

ENSEMBL: ENSMUSP00000029727 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000029727] [ENSMUST00000107675] [ENSMUST00000107678] [ENSMUST00000107679] [ENSMUST00000154148]

Predicted Effect

possibly damaging
Transcript: ENSMUST00000029727
AA Change: Y232F

PolyPhen 2 Score 0.942 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000029727
Gene: ENSMUSG00000028086
AA Change: Y232F

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
low complexity region	139	146	N/A	INTRINSIC
FBOX	206	246	3.7e-8	SMART
WD40	291	329	3.14e-6	SMART
WD40	332	369	2.1e-7	SMART
WD40	372	409	7.55e-9	SMART
WD40	412	449	2.22e-6	SMART
WD40	452	489	1.07e-8	SMART
WD40	492	529	1.75e-4	SMART
WD40	532	572	2.32e-9	SMART
WD40	575	623	2.37e2	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000107675
AA Change: Y192F

PolyPhen 2 Score 0.577 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000103302
Gene: ENSMUSG00000028086
AA Change: Y192F

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
AA Change: Y313F

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000103305
Gene: ENSMUSG00000028086
AA Change: Y313F

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
AA Change: Y313F

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000103306
Gene: ENSMUSG00000028086
AA Change: Y313F

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

0.124

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.7%
20x: 93.7%

Validation Efficiency

98% (101/103)

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: 92 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
9930012K11Rik	C	T	14: 70,156,458	V243I	probably benign	Het
Acadvl	C	T	11: 70,011,184	G485S	probably benign	Het
Acap3	T	A	4: 155,902,451		probably benign	Het
Adamts19	A	G	18: 58,890,284	I250M	probably damaging	Het
AF067061	A	T	13: 120,264,150	T117S	probably damaging	Het
Amacr	T	A	15: 10,983,410	I102N	probably damaging	Het
Apob	A	G	12: 8,015,741	T4237A	probably benign	Het
Bbs10	A	G	10: 111,301,134	K703E	probably benign	Het
Bicd1	A	T	6: 149,519,254		probably benign	Het
Caskin2	T	A	11: 115,807,299	E49V	probably damaging	Het
Cemip	T	A	7: 83,973,241	I577F	probably benign	Het
Chrnb1	T	C	11: 69,795,675	S40G	possibly damaging	Het
Ctif	C	T	18: 75,521,561	C298Y	probably benign	Het
Cul9	A	C	17: 46,530,051	H764Q	probably benign	Het
Cwf19l2	T	A	9: 3,458,839	C763S	probably damaging	Het
Dhx57	A	T	17: 80,242,167		probably null	Het
Dnhd1	G	A	7: 105,703,964	D2775N	probably benign	Het
Enpp1	A	T	10: 24,661,935	M384K	possibly damaging	Het
Fat2	T	C	11: 55,311,318	N310S	probably benign	Het
Fcamr	T	A	1: 130,812,686	S281T	possibly damaging	Het
Gm10762	C	T	2: 128,967,186	W81*	probably null	Het
Gm5592	A	G	7: 41,155,890		probably benign	Het
Gm5745	T	C	9: 73,175,698		noncoding transcript	Het
Gm6185	G	C	1: 161,213,254		noncoding transcript	Het
Hid1	T	A	11: 115,355,299	N382Y	probably damaging	Het
Hoxa10	A	T	6: 52,232,589	F68I	probably damaging	Het
Ift88	T	A	14: 57,441,869		probably null	Het
Ighg2b	A	T	12: 113,306,391	*336R	probably null	Het
Ighv7-2	A	C	12: 113,912,272	L37R	probably damaging	Het
Kcnd3	C	T	3: 105,658,766	A421V	probably damaging	Het
Kcnn3	G	C	3: 89,667,289	V703L	possibly damaging	Het
Kiz	C	A	2: 146,891,069	S388R	probably damaging	Het
Klhl20	G	A	1: 161,093,763	Q41*	probably null	Het
Krt31	T	C	11: 100,047,784	I328V	possibly damaging	Het
Lama4	A	T	10: 39,033,053	I330L	probably benign	Het
Lipo2	A	T	19: 33,745,751	S213T	probably benign	Het
Lrsam1	A	T	2: 32,926,792	I723N	probably damaging	Het
Man2b2	G	A	5: 36,815,521	R550W	probably damaging	Het
Map4k5	A	T	12: 69,841,984	L224*	probably null	Het
Mast3	A	G	8: 70,780,366	S1101P	probably damaging	Het
Mertk	A	G	2: 128,801,305	S875G	probably benign	Het
Mmel1	A	G	4: 154,887,897	M302V	probably benign	Het
Mrgpra3	T	A	7: 47,589,968	H70L	possibly damaging	Het
Myh3	T	A	11: 67,089,010	S592T	probably benign	Het
Nbeal2	T	C	9: 110,636,315	I451V	possibly damaging	Het
Nup155	T	A	15: 8,128,526	V489D	possibly damaging	Het
Obscn	T	A	11: 59,022,333	T6300S	probably benign	Het
Olfr1294	G	T	2: 111,537,452	T279K	probably damaging	Het
Olfr1377	T	A	11: 50,985,083	C127*	probably null	Het
Olfr290	A	C	7: 84,916,426	I216L	possibly damaging	Het
Olfr350	A	G	2: 36,850,876	M277V	probably benign	Het
Oprm1	A	G	10: 6,829,036	I146V	probably damaging	Het
Otub1	A	T	19: 7,204,429	D27E	probably damaging	Het
Pik3ca	T	C	3: 32,437,982	V243A	probably benign	Het
Pla2g12b	G	A	10: 59,416,514		probably null	Het
Plekha8	A	G	6: 54,624,561	D321G	probably damaging	Het
Pprc1	T	C	19: 46,071,356		probably benign	Het
Prkdc	A	G	16: 15,650,712	D129G	possibly damaging	Het
Rbms3	C	T	9: 116,944,373		probably benign	Het
Rictor	T	A	15: 6,791,680	V1495D	probably benign	Het
Rpl31-ps21	T	C	5: 21,119,509		noncoding transcript	Het
Ryr3	A	T	2: 112,652,745	I4219N	probably damaging	Het
Sbf2	G	A	7: 110,377,939		probably benign	Het
Scn10a	C	T	9: 119,638,672	A801T	probably damaging	Het
Scn9a	T	A	2: 66,483,749	Y1866F	possibly damaging	Het
Sec1	A	C	7: 45,679,303	Y107D	probably damaging	Het
Sema6d	C	T	2: 124,662,294	T619M	possibly damaging	Het
Sh2b3	C	A	5: 121,828,555		probably benign	Het
Slc2a4	A	G	11: 69,946,587	V44A	probably damaging	Het
Slc5a12	T	C	2: 110,621,740	I326T	possibly damaging	Het
Smarca5	T	C	8: 80,708,680		probably null	Het
Smarcd2	A	G	11: 106,266,531		probably null	Het
Snrpa1	A	T	7: 66,069,573		probably benign	Het
Sptbn5	T	G	2: 120,067,968	K470Q	probably benign	Het
Stard9	T	G	2: 120,695,941	V893G	possibly damaging	Het
Stx8	T	G	11: 67,973,273	V53G	possibly damaging	Het
Sv2c	A	T	13: 95,985,949	W440R	probably damaging	Het
Tmem181a	A	T	17: 6,280,665	I67F	probably benign	Het
Tmprss7	C	T	16: 45,663,316	C565Y	probably damaging	Het
Trafd1	A	T	5: 121,378,498	L109H	probably damaging	Het
Trpv4	A	G	5: 114,630,022	I422T	possibly damaging	Het
Usp24	T	A	4: 106,416,047	Y2210N	probably damaging	Het
Vmn1r236	A	T	17: 21,286,940	N107Y	probably damaging	Het
Vmn2r13	A	T	5: 109,174,072	I253K	probably damaging	Het
Vmn2r2	T	A	3: 64,134,539	I252F	probably damaging	Het
Vsig8	A	G	1: 172,559,638	D27G	probably damaging	Het
Wdr92	T	A	11: 17,227,165	N174K	probably damaging	Het
Wiz	A	T	17: 32,356,437	Y908*	probably null	Het
Wnk1	A	T	6: 119,962,438	S1113T	probably benign	Het
Zdhhc1	CGGGGG	CGGGGGG	8: 105,483,744		probably null	Het
Zfp691	G	T	4: 119,170,567	T156K	probably damaging	Het
Zfp791	A	T	8: 85,110,406	D276E	probably benign	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
R0043:Fbxw7	UTSW	3	84972567	intron	probably benign
R0312:Fbxw7	UTSW	3	84967569	intron	probably benign
R0595:Fbxw7	UTSW	3	84977367	intron	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
R4776:Fbxw7	UTSW	3	84925689	missense	possibly damaging	0.53
R4799:Fbxw7	UTSW	3	84903861	nonsense	probably null
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	intron	probably null

Predicted Primers

PCR Primer
(F):5'- TGAAATGCAGTAGTCCTAGCAAGATG -3'
(R):5'- AAATCAGGTGGCCTCCTTTCC -3'

Sequencing Primer
(F):5'- TGCTCAGCCTGGGTAGAGTAAC -3'
(R):5'- TCCTGTTGGGATCAAGGAAGTGAAC -3'

Posted On

2016-03-01