Mutagenetix > Incidental Mutation

Incidental Mutation 'R6823:Fbxw7'

537713

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

Accession Numbers

Is this an essential gene?

Essential (E-score: 1.000) question?

Stock #

R6823 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

84815268-84979198 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

G to C at 84958627 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Aspartic acid at position 118 (E118D)

Ref Sequence

ENSEMBL: ENSMUSP00000103302 (fasta)

Gene Model

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

AlphaFold

Q8VBV4

Predicted Effect

probably benign
Transcript: ENSMUST00000029727
AA Change: E158D

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000029727
Gene: ENSMUSG00000028086
AA Change: E158D

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

probably benign
Transcript: ENSMUST00000107675
AA Change: E118D

PolyPhen 2 Score 0.326 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000103302
Gene: ENSMUSG00000028086
AA Change: E118D

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: E239D

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000103305
Gene: ENSMUSG00000028086
AA Change: E239D

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: E239D

PolyPhen 2 Score 0.005 (Sensitivity: 0.97; Specificity: 0.74)

SMART Domains

Protein: ENSMUSP00000103306
Gene: ENSMUSG00000028086
AA Change: E239D

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: ENSMUST00000154148

SMART Domains

Protein: ENSMUSP00000116393
Gene: ENSMUSG00000102805

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

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.5%
20x: 98.4%

Validation Efficiency

98% (81/83)

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: 81 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adcy8	T	G	15: 64,754,886		probably null	Het
Adgrv1	A	G	13: 81,557,081	F1537L	probably damaging	Het
Aggf1	T	C	13: 95,364,723	S384G	probably benign	Het
Anxa8	A	T	14: 34,094,765	D204V	possibly damaging	Het
Asap3	A	T	4: 136,227,572	E71V	possibly damaging	Het
BC024139	T	C	15: 76,119,746	*773W	probably null	Het
Bckdhb	T	C	9: 83,953,761	V106A	possibly damaging	Het
Cep250	A	G	2: 155,981,459	D1010G	probably benign	Het
Chrd	T	A	16: 20,734,736	L243Q	probably damaging	Het
Cib2	G	T	9: 54,549,891	L30I	possibly damaging	Het
Cpsf7	T	A	19: 10,532,884	L113*	probably null	Het
Cubn	T	A	2: 13,445,029	I895L	probably benign	Het
Cyp24a1	C	A	2: 170,487,979	R351I	probably benign	Het
Cyp2a12	A	T	7: 27,034,156	D320V	possibly damaging	Het
Dact1	C	G	12: 71,317,939	P498R	probably benign	Het
Diaph1	T	A	18: 37,876,383		probably null	Het
Dnah7a	A	T	1: 53,456,704	I3198N	probably benign	Het
Dopey2	A	T	16: 93,755,485	I271F	possibly damaging	Het
Erich3	C	A	3: 154,727,437	F349L	probably damaging	Het
Fam187b	G	C	7: 30,989,290	V358L	probably benign	Het
Fat4	T	A	3: 38,983,939	H3913Q	probably benign	Het
Fgf1	A	G	18: 38,847,108	I71T	probably damaging	Het
Fryl	A	T	5: 73,065,217	I2007K	probably damaging	Het
Galnt2	C	G	8: 124,324,011	P130A	probably benign	Het
H1fx	G	A	6: 87,981,302	R19C	probably damaging	Het
Hmga2	A	C	10: 120,476,024	S14A	possibly damaging	Het
Hoxb4	C	T	11: 96,318,654		probably benign	Het
Hr	A	T	14: 70,565,374	I756F	probably damaging	Het
Hrasls5	A	T	19: 7,639,496		probably benign	Het
Hspa1b	A	T	17: 34,958,185	S275T	probably benign	Het
Ikbkap	A	G	4: 56,787,939	Y331H	probably damaging	Het
Kcnh1	T	C	1: 192,505,289	*99R	probably null	Het
Kit	C	A	5: 75,652,649	L864I	probably benign	Het
Klk14	A	T	7: 43,694,456	K196*	probably null	Het
Lmod1	A	G	1: 135,325,167	N53S	probably damaging	Het
Myh13	T	C	11: 67,356,158	M1235T	probably benign	Het
Neurl3	T	A	1: 36,268,704	K175*	probably null	Het
Nlgn2	T	A	11: 69,825,924	K597M	probably damaging	Het
Npdc1	T	C	2: 25,409,109	M306T	probably damaging	Het
Obscn	C	T	11: 59,067,943		probably null	Het
Olfr404-ps1	T	C	11: 74,239,696	L44P	probably damaging	Het
Olfr553	G	A	7: 102,614,486	L168F	probably damaging	Het
Olfr913	T	C	9: 38,594,905	I228T	possibly damaging	Het
Pbrm1	A	T	14: 31,084,790	Y1042F	probably damaging	Het
Pclo	T	A	5: 14,677,907		probably benign	Het
Peg10	CATCAGGATCCCCATCAGGATGCACATCAGGATCCACATCAGGATGCACATCAGGATC	CATC	6: 4,756,431		probably benign	Het
Phf12	C	T	11: 78,022,511	Q430*	probably null	Het
Pld3	C	T	7: 27,535,897	R302H	probably damaging	Het
Plekha5	T	C	6: 140,525,858	S112P	probably benign	Het
Pmfbp1	T	A	8: 109,530,307	S548T	possibly damaging	Het
Ppa1	A	T	10: 61,667,603	I220F	probably damaging	Het
Ppp2r3d	A	G	9: 124,439,078		probably benign	Het
Psmg2	A	T	18: 67,648,857	E164D	possibly damaging	Het
Rarb	T	C	14: 16,443,824	R155G	probably damaging	Het
Rnf215	T	C	11: 4,136,609	L162S	probably damaging	Het
Rsf1	GGCG	GGCGACGGCCGCG	7: 97,579,906		probably benign	Het
Rtkn2	G	A	10: 68,026,632	V330M	probably damaging	Het
Slc16a4	A	T	3: 107,311,498	I472F	probably benign	Het
Snx14	T	C	9: 88,394,382	N617D	possibly damaging	Het
Spire2	T	C	8: 123,356,727	V150A	probably damaging	Het
Sptbn1	C	A	11: 30,114,787	R1904M	probably damaging	Het
Swap70	A	G	7: 110,281,303	E575G	possibly damaging	Het
Tbxas1	A	T	6: 38,919,153	M1L	possibly damaging	Het
Tenm3	A	T	8: 48,256,837	V1688D	probably damaging	Het
Tgfbr3	A	T	5: 107,149,914	S207T	probably damaging	Het
Timm44	A	G	8: 4,267,282	F248L	probably damaging	Het
Tmem161a	T	C	8: 70,181,199	L170P	probably damaging	Het
Tmem63a	A	T	1: 180,960,470	Y263F	possibly damaging	Het
Tnfsf9	C	A	17: 57,105,513	L28I	probably benign	Het
Tph2	T	A	10: 115,174,106	N183I	probably benign	Het
Ttyh1	T	C	7: 4,122,529	I60T	probably damaging	Het
Ubn1	T	G	16: 5,064,547	S48A	probably damaging	Het
Ubr5	T	C	15: 37,989,598	N2019S	probably benign	Het
Wbp2	T	C	11: 116,086,910	N6D	probably benign	Het
Wdr59	T	A	8: 111,459,040	E810V	possibly damaging	Het
Wiz	T	C	17: 32,360,421	D220G	probably damaging	Het
Yipf7	A	G	5: 69,517,070	L244P	probably damaging	Het
Zdhhc17	T	C	10: 110,955,111	T366A	possibly damaging	Het
Zfp169	A	T	13: 48,490,996		probably benign	Het
Zfp707	C	T	15: 75,969,723		probably benign	Het
Zfp788	A	G	7: 41,649,560	H540R	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
R4776:Fbxw7	UTSW	3	84925689	missense	possibly damaging	0.53
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
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'- GGGGCAAGCTTAAGGTCTTAC -3'
(R):5'- GCGTGCTATTTAAGTGTACACC -3'

Sequencing Primer
(F):5'- GCTTAAGGTCTTACGTATAAGCAGG -3'
(R):5'- ACCCTACATCTCTTAGCAGGTAG -3'

Posted On

2018-10-18