Mutagenetix > Incidental Mutation

Incidental Mutation 'R1921:Fbxl5'

213043

Institutional Source

Beutler Lab

Gene Symbol

Fbxl5

Ensembl Gene

ENSMUSG00000039753

Gene Name

F-box and leucine-rich repeat protein 5

Synonyms

Fbl4, Fir4

MMRRC Submission

039939-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1921 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

43901958-43939529 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 43922832 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Aspartic acid at position 189 (E189D)

Ref Sequence

ENSEMBL: ENSMUSP00000109681 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000047857] [ENSMUST00000087465] [ENSMUST00000114047] [ENSMUST00000119523] [ENSMUST00000121736] [ENSMUST00000124610] [ENSMUST00000196483] [ENSMUST00000199055]

AlphaFold

Q8C2S5

Predicted Effect

probably benign
Transcript: ENSMUST00000047857
AA Change: E195D

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

SMART Domains

Protein: ENSMUSP00000045792
Gene: ENSMUSG00000039753
AA Change: E195D

Domain	Start	End	E-Value	Type
Pfam:Hemerythrin	6	138	1.3e-10	PFAM
FBOX	208	248	2.31e-9	SMART
low complexity region	289	310	N/A	INTRINSIC
LRR	355	379	2.43e2	SMART
LRR	382	407	4.87e-4	SMART
low complexity region	481	492	N/A	INTRINSIC
LRR	596	621	2.45e0	SMART
LRR	624	649	4.65e-1	SMART
Blast:LRR	650	681	2e-13	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000087465
AA Change: E195D

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

SMART Domains

Protein: ENSMUSP00000084733
Gene: ENSMUSG00000039753
AA Change: E195D

Domain	Start	End	E-Value	Type
Pfam:Hemerythrin	6	138	4.3e-15	PFAM
FBOX	208	248	2.31e-9	SMART
low complexity region	289	310	N/A	INTRINSIC
LRR	355	379	2.43e2	SMART
LRR	382	407	4.87e-4	SMART
low complexity region	481	492	N/A	INTRINSIC
LRR	596	621	1.23e2	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000114047
AA Change: E189D

PolyPhen 2 Score 0.164 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000109681
Gene: ENSMUSG00000039753
AA Change: E189D

Domain	Start	End	E-Value	Type
Pfam:Hemerythrin	19	132	4.4e-11	PFAM
FBOX	202	242	2.31e-9	SMART
low complexity region	283	304	N/A	INTRINSIC
LRR	349	373	2.43e2	SMART
LRR	376	401	4.87e-4	SMART
low complexity region	475	486	N/A	INTRINSIC
LRR	590	615	2.45e0	SMART
LRR	618	643	4.65e-1	SMART
Blast:LRR	644	675	2e-13	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000119523
AA Change: E178D

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000113557
Gene: ENSMUSG00000039753
AA Change: E178D

Domain	Start	End	E-Value	Type
Pfam:Hemerythrin	6	121	2.2e-9	PFAM
FBOX	191	231	2.31e-9	SMART
low complexity region	272	293	N/A	INTRINSIC
LRR	338	362	2.43e2	SMART
LRR	365	390	4.87e-4	SMART
low complexity region	464	475	N/A	INTRINSIC
LRR	579	604	2.45e0	SMART
LRR	607	632	4.65e-1	SMART
Blast:LRR	633	664	2e-13	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000121736
AA Change: E152D

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

SMART Domains

Protein: ENSMUSP00000112444
Gene: ENSMUSG00000039753
AA Change: E152D

Domain	Start	End	E-Value	Type
PDB:3V5Z\|B	1	118	2e-71	PDB
FBOX	165	205	2.31e-9	SMART
low complexity region	246	267	N/A	INTRINSIC
LRR	312	336	2.43e2	SMART
LRR	339	364	4.87e-4	SMART
low complexity region	438	449	N/A	INTRINSIC
LRR	553	578	1.23e2	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000124421

Predicted Effect

probably benign
Transcript: ENSMUST00000124610
AA Change: E195D

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

SMART Domains

Protein: ENSMUSP00000116720
Gene: ENSMUSG00000039753
AA Change: E195D

Domain	Start	End	E-Value	Type
Pfam:Hemerythrin	6	138	5.7e-12	PFAM
FBOX	208	248	1.5e-11	SMART
low complexity region	289	310	N/A	INTRINSIC
LRR	355	379	1e0	SMART
LRR	382	407	2e-6	SMART
low complexity region	481	492	N/A	INTRINSIC
LRR	596	621	1e-2	SMART
LRR	624	649	1.9e-3	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000196483
AA Change: E195D

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

SMART Domains

Protein: ENSMUSP00000143703
Gene: ENSMUSG00000039753
AA Change: E195D

Domain	Start	End	E-Value	Type
Pfam:Hemerythrin	6	138	1.3e-10	PFAM
FBOX	208	248	2.31e-9	SMART
low complexity region	289	309	N/A	INTRINSIC
LRR	354	378	2.43e2	SMART
LRR	381	406	4.87e-4	SMART
low complexity region	480	491	N/A	INTRINSIC
LRR	595	620	2.45e0	SMART
LRR	623	648	4.65e-1	SMART
Blast:LRR	649	680	2e-13	BLAST

Predicted Effect

unknown
Transcript: ENSMUST00000141902
AA Change: E115D

SMART Domains

Protein: ENSMUSP00000120338
Gene: ENSMUSG00000039753
AA Change: E115D

Domain	Start	End	E-Value	Type
PDB:3V5Z\|B	2	82	3e-43	PDB
FBOX	129	169	2.31e-9	SMART
low complexity region	210	231	N/A	INTRINSIC
LRR	276	300	2.43e2	SMART
LRR	303	328	4.87e-4	SMART
low complexity region	402	413	N/A	INTRINSIC
LRR	517	542	2.45e0	SMART
LRR	545	570	4.65e-1	SMART
Blast:LRR	571	602	3e-13	BLAST

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000143316

Predicted Effect

probably benign
Transcript: ENSMUST00000199055

SMART Domains

Protein: ENSMUSP00000142582
Gene: ENSMUSG00000039753

Domain	Start	End	E-Value	Type
Pfam:Hemerythrin	6	105	6.1e-7	PFAM

Coding Region Coverage

1x: 97.3%
3x: 96.7%
10x: 94.9%
20x: 91.3%

Validation Efficiency

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 belongs to the Fbls class and, in addition to an F-box, contains several tandem leucine-rich repeats. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Aug 2010]
PHENOTYPE: Mice homozygous for a null mutation display embryonic lethality before turning of the embryo with iron overload, growth retardation, and hemorrhage. Mice heterozygous for a knock-out allele exhibit abnormal iron homeostasis when fed a low iron diet. [provided by MGI curators]

Allele List at MGI

All alleles(10) : Gene trapped(10)

Other mutations in this stock

Total: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A2m	C	A	6: 121,631,571 (GRCm39)	L623M	probably benign	Het
Abhd2	T	C	7: 78,998,104 (GRCm39)	I212T	possibly damaging	Het
Adam7	A	C	14: 68,750,074 (GRCm39)	S449A	possibly damaging	Het
Alkbh2	C	T	5: 114,262,287 (GRCm39)	E148K	probably damaging	Het
Aox3	T	C	1: 58,219,810 (GRCm39)	Y1137H	probably damaging	Het
Atp11b	T	C	3: 35,888,474 (GRCm39)	Y715H	probably damaging	Het
Atrn	A	G	2: 130,836,971 (GRCm39)	Y1145C	probably damaging	Het
Btbd7	A	G	12: 102,760,055 (GRCm39)	I631T	probably benign	Het
Cadps	T	C	14: 12,465,859 (GRCm38)	K1017R	possibly damaging	Het
Cfap45	A	G	1: 172,372,679 (GRCm39)	E458G	probably damaging	Het
Cptp	C	T	4: 155,950,995 (GRCm39)	R157H	probably damaging	Het
Dcbld1	A	C	10: 52,195,747 (GRCm39)	E318D	possibly damaging	Het
Ddr2	G	T	1: 169,831,814 (GRCm39)	P197Q	probably damaging	Het
Dlg5	T	C	14: 24,226,639 (GRCm39)	Y421C	probably damaging	Het
Dlgap2	A	G	8: 14,893,624 (GRCm39)	K980E	probably benign	Het
Drc7	T	C	8: 95,782,644 (GRCm39)	V3A	unknown	Het
Dst	T	C	1: 34,200,110 (GRCm39)	V96A	probably damaging	Het
Ect2l	T	C	10: 18,018,752 (GRCm39)	D548G	possibly damaging	Het
Efcab10	A	T	12: 33,448,434 (GRCm39)	Y89F	probably benign	Het
Eif1ad	CGAGGAGGAGGAGGAGGAGG	CGAGGAGGAGGAGGAGG	19: 5,420,086 (GRCm39)		probably benign	Het
Entpd6	A	G	2: 150,600,732 (GRCm39)	T147A	probably damaging	Het
Fer1l6	T	A	15: 58,497,080 (GRCm39)	S1217T	probably damaging	Het
Frem2	A	T	3: 53,560,916 (GRCm39)	V1197D	possibly damaging	Het
Fsip2	T	A	2: 82,811,127 (GRCm39)	L2482*	probably null	Het
Fsip2	A	T	2: 82,817,164 (GRCm39)	D4299V	probably benign	Het
Gipc3	T	A	10: 81,174,049 (GRCm39)	I242F	probably damaging	Het
Hoxb1	T	A	11: 96,256,938 (GRCm39)	Y96N	probably damaging	Het
Ibsp	A	G	5: 104,458,078 (GRCm39)	E205G	probably damaging	Het
Ibtk	A	G	9: 85,585,135 (GRCm39)	S1170P	probably benign	Het
Igfn1	A	G	1: 135,893,801 (GRCm39)		probably null	Het
Iqsec1	A	G	6: 90,639,877 (GRCm39)	S954P	probably benign	Het
Kalrn	A	T	16: 34,212,463 (GRCm39)	D28E	probably benign	Het
Lrmda	T	C	14: 22,627,938 (GRCm39)	F52L	probably damaging	Het
Lrp2	T	C	2: 69,353,631 (GRCm39)	D543G	probably damaging	Het
Lrrtm3	T	C	10: 63,924,157 (GRCm39)	T337A	probably benign	Het
Marf1	C	T	16: 13,946,465 (GRCm39)	D1219N	possibly damaging	Het
Mkln1	A	G	6: 31,405,113 (GRCm39)	K118R	probably benign	Het
Nedd4l	T	C	18: 65,300,646 (GRCm39)		probably null	Het
Neu2	A	G	1: 87,525,023 (GRCm39)	E336G	probably benign	Het
Nfasc	A	G	1: 132,538,543 (GRCm39)	F448S	probably damaging	Het
Nlrx1	C	A	9: 44,165,431 (GRCm39)	E822*	probably null	Het
Nr5a1	T	C	2: 38,584,108 (GRCm39)	Y437C	probably damaging	Het
Or4c119	A	G	2: 88,986,925 (GRCm39)	V198A	probably benign	Het
Or7a37	T	A	10: 78,805,975 (GRCm39)	L164*	probably null	Het
Or8b38	T	C	9: 37,972,981 (GRCm39)	Y122H	probably damaging	Het
Phtf1	C	T	3: 103,876,438 (GRCm39)	Q13*	probably null	Het
Pnldc1	A	G	17: 13,107,815 (GRCm39)	L525P	possibly damaging	Het
Ppl	T	A	16: 4,923,988 (GRCm39)	D162V	possibly damaging	Het
Prkdc	T	A	16: 15,532,079 (GRCm39)	S1448T	possibly damaging	Het
Ptgdr	A	G	14: 45,090,738 (GRCm39)	I340T	probably benign	Het
Recql	T	C	6: 142,311,315 (GRCm39)	I458M	probably benign	Het
Rrbp1	A	T	2: 143,830,211 (GRCm39)	V652E	probably benign	Het
Rtp1	T	A	16: 23,250,160 (GRCm39)	I175N	probably damaging	Het
Ryr1	A	G	7: 28,754,369 (GRCm39)	M3523T	probably damaging	Het
S100a16	T	C	3: 90,449,703 (GRCm39)	L62P	probably damaging	Het
Samd11	T	C	4: 156,333,166 (GRCm39)	E364G	probably damaging	Het
Satb1	C	A	17: 52,049,143 (GRCm39)	G603*	probably null	Het
Shroom3	T	A	5: 93,110,224 (GRCm39)		probably null	Het
Slc25a15	A	G	8: 22,885,777 (GRCm39)	S3P	probably benign	Het
Socs2	A	T	10: 95,248,900 (GRCm39)	L71*	probably null	Het
Sptbn1	T	C	11: 30,054,469 (GRCm39)	E2208G	probably damaging	Het
St14	A	G	9: 31,001,166 (GRCm39)	V855A	possibly damaging	Het
Susd1	T	A	4: 59,412,191 (GRCm39)	T121S	probably benign	Het
Svs3b	A	T	2: 164,097,848 (GRCm39)	S158T	probably benign	Het
Synpo	C	T	18: 60,736,661 (GRCm39)	M428I	probably benign	Het
Syt10	C	T	15: 89,674,979 (GRCm39)	D456N	probably damaging	Het
Taar4	A	G	10: 23,837,239 (GRCm39)	D283G	probably damaging	Het
Tango6	T	A	8: 107,415,426 (GRCm39)	D82E	probably benign	Het
Tcof1	T	C	18: 60,971,927 (GRCm39)	T127A	possibly damaging	Het
Tle3	G	A	9: 61,318,622 (GRCm39)		probably null	Het
Tmem45a	A	G	16: 56,642,665 (GRCm39)	F169L	probably benign	Het
Trp53rkb	T	A	2: 166,637,743 (GRCm39)	V233E	probably damaging	Het
Ttc7b	C	T	12: 100,381,389 (GRCm39)		probably null	Het
Tubgcp3	A	T	8: 12,671,932 (GRCm39)	L770*	probably null	Het
Tut1	G	A	19: 8,943,466 (GRCm39)	G851D	probably benign	Het
Ubr1	G	A	2: 120,761,449 (GRCm39)	T576I	probably benign	Het
Vmn1r125	T	A	7: 21,006,530 (GRCm39)	Y143N	probably damaging	Het
Vmn2r120	T	A	17: 57,831,839 (GRCm39)	I317F	probably benign	Het
Vmn2r95	T	A	17: 18,644,575 (GRCm39)	N70K	probably benign	Het
Vps35l	A	G	7: 118,432,971 (GRCm39)	N568S	probably damaging	Het
Wdr59	A	T	8: 112,213,582 (GRCm39)	L311*	probably null	Het
Wnt2	A	G	6: 18,030,252 (GRCm39)	L12P	unknown	Het
Xrn1	T	C	9: 95,881,550 (GRCm39)	I700T	probably benign	Het
Ypel1	A	G	16: 16,900,443 (GRCm39)	H98R	probably benign	Het
Zfp219	T	C	14: 52,245,691 (GRCm39)	T434A	probably benign	Het
Zik1	A	C	7: 10,223,943 (GRCm39)	C385G	probably damaging	Het

Other mutations in Fbxl5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00236:Fbxl5	APN	5	43,922,678 (GRCm39)	missense	probably damaging	1.00
IGL00797:Fbxl5	APN	5	43,915,743 (GRCm39)	missense	probably damaging	1.00
IGL00811:Fbxl5	APN	5	43,915,567 (GRCm39)	missense	probably damaging	1.00
IGL01065:Fbxl5	APN	5	43,902,676 (GRCm39)	missense	probably damaging	1.00
IGL01626:Fbxl5	APN	5	43,916,047 (GRCm39)	missense	probably benign	0.00
IGL02285:Fbxl5	APN	5	43,922,690 (GRCm39)	missense	possibly damaging	0.88
D3080:Fbxl5	UTSW	5	43,915,708 (GRCm39)	missense	probably benign	0.00
PIT4498001:Fbxl5	UTSW	5	43,908,323 (GRCm39)	missense	possibly damaging	0.73
R0195:Fbxl5	UTSW	5	43,928,140 (GRCm39)	missense	probably damaging	1.00
R0647:Fbxl5	UTSW	5	43,925,411 (GRCm39)	missense	probably damaging	0.98
R1540:Fbxl5	UTSW	5	43,915,978 (GRCm39)	missense	possibly damaging	0.92
R1545:Fbxl5	UTSW	5	43,928,140 (GRCm39)	missense	probably damaging	1.00
R1569:Fbxl5	UTSW	5	43,922,803 (GRCm39)	missense	probably damaging	1.00
R3081:Fbxl5	UTSW	5	43,908,222 (GRCm39)	missense	probably damaging	1.00
R3776:Fbxl5	UTSW	5	43,915,618 (GRCm39)	missense	possibly damaging	0.57
R4096:Fbxl5	UTSW	5	43,915,583 (GRCm39)	missense	probably benign	0.19
R4275:Fbxl5	UTSW	5	43,920,114 (GRCm39)	intron	probably benign
R4383:Fbxl5	UTSW	5	43,920,305 (GRCm39)	intron	probably benign
R4469:Fbxl5	UTSW	5	43,925,528 (GRCm39)	missense	probably damaging	1.00
R4654:Fbxl5	UTSW	5	43,922,771 (GRCm39)	missense	probably damaging	0.99
R5067:Fbxl5	UTSW	5	43,916,114 (GRCm39)	missense	probably benign	0.00
R5093:Fbxl5	UTSW	5	43,930,896 (GRCm39)	missense	probably damaging	1.00
R5696:Fbxl5	UTSW	5	43,916,182 (GRCm39)	missense	possibly damaging	0.93
R5738:Fbxl5	UTSW	5	43,920,170 (GRCm39)	missense	probably benign	0.30
R6029:Fbxl5	UTSW	5	43,922,746 (GRCm39)	missense	probably damaging	0.96
R6185:Fbxl5	UTSW	5	43,978,894 (GRCm39)	missense	probably benign	0.02
R6842:Fbxl5	UTSW	5	43,930,928 (GRCm39)	missense	probably damaging	1.00
R7234:Fbxl5	UTSW	5	43,915,562 (GRCm39)	missense	probably benign	0.08
R7563:Fbxl5	UTSW	5	43,978,891 (GRCm39)	missense	probably benign	0.00
R7653:Fbxl5	UTSW	5	43,916,116 (GRCm39)	missense	probably benign
R7842:Fbxl5	UTSW	5	43,915,945 (GRCm39)	missense	probably damaging	1.00
R7860:Fbxl5	UTSW	5	43,916,018 (GRCm39)	missense	probably benign	0.00
R8139:Fbxl5	UTSW	5	43,916,087 (GRCm39)	nonsense	probably null
R8393:Fbxl5	UTSW	5	43,925,433 (GRCm39)	missense	possibly damaging	0.94
R8727:Fbxl5	UTSW	5	43,908,362 (GRCm39)	splice site	probably benign
R9616:Fbxl5	UTSW	5	43,916,159 (GRCm39)	missense	probably benign
RF012:Fbxl5	UTSW	5	43,930,847 (GRCm39)	missense	probably damaging	1.00
X0065:Fbxl5	UTSW	5	43,918,140 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- ACCTCTTGCCCAATGAACAGG -3'
(R):5'- ACTGATGAAGTATGATCTGGGCTG -3'

Sequencing Primer
(F):5'- CTCTTGCCCAATGAACAGGGTAAAG -3'
(R):5'- CTCACGGGTTCTTAACAAGTTCAAC -3'

Posted On

2014-07-14