Incidental Mutation 'R4654:Fbxl5'
ID 351529
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 041914-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4654 (G1)
Quality Score 225
Status Validated
Chromosome 5
Chromosomal Location 43901958-43939529 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 43922771 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Isoleucine to Phenylalanine at position 216 (I216F)
Ref Sequence ENSEMBL: ENSMUSP00000143703 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000047857] [ENSMUST00000087465] [ENSMUST00000114047] [ENSMUST00000119523] [ENSMUST00000121736] [ENSMUST00000124610] [ENSMUST00000196483] [ENSMUST00000199055]
AlphaFold Q8C2S5
Predicted Effect probably damaging
Transcript: ENSMUST00000047857
AA Change: I216F

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000045792
Gene: ENSMUSG00000039753
AA Change: I216F

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000087465
AA Change: I216F

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000084733
Gene: ENSMUSG00000039753
AA Change: I216F

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000114047
AA Change: I210F

PolyPhen 2 Score 0.965 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000109681
Gene: ENSMUSG00000039753
AA Change: I210F

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000119523
AA Change: I199F

PolyPhen 2 Score 0.972 (Sensitivity: 0.77; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000113557
Gene: ENSMUSG00000039753
AA Change: I199F

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000121736
AA Change: I173F

PolyPhen 2 Score 0.980 (Sensitivity: 0.75; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000112444
Gene: ENSMUSG00000039753
AA Change: I173F

DomainStartEndE-ValueType
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 damaging
Transcript: ENSMUST00000124610
AA Change: I216F

PolyPhen 2 Score 0.972 (Sensitivity: 0.77; Specificity: 0.96)
SMART Domains Protein: ENSMUSP00000116720
Gene: ENSMUSG00000039753
AA Change: I216F

DomainStartEndE-ValueType
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 noncoding transcript
Transcript: ENSMUST00000143316
Predicted Effect probably damaging
Transcript: ENSMUST00000196483
AA Change: I216F

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)
SMART Domains Protein: ENSMUSP00000143703
Gene: ENSMUSG00000039753
AA Change: I216F

DomainStartEndE-ValueType
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: I136F
SMART Domains Protein: ENSMUSP00000120338
Gene: ENSMUSG00000039753
AA Change: I136F

DomainStartEndE-ValueType
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 probably benign
Transcript: ENSMUST00000199055
SMART Domains Protein: ENSMUSP00000142582
Gene: ENSMUSG00000039753

DomainStartEndE-ValueType
Pfam:Hemerythrin 6 105 6.1e-7 PFAM
Meta Mutation Damage Score 0.3975 question?
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.6%
  • 10x: 97.2%
  • 20x: 95.2%
Validation Efficiency 97% (98/101)
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: 90 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam3 A T 8: 25,193,819 (GRCm39) C398S probably damaging Het
Adamts10 A G 17: 33,756,304 (GRCm39) K316E possibly damaging Het
Ap1m1 T C 8: 73,006,717 (GRCm39) F238L possibly damaging Het
Aph1a T A 3: 95,803,088 (GRCm39) D180E probably benign Het
Atp9b A G 18: 80,935,093 (GRCm39) F201L probably benign Het
Btbd9 A C 17: 30,704,561 (GRCm39) probably benign Het
C2cd5 T C 6: 142,975,910 (GRCm39) T768A probably benign Het
Casq1 C T 1: 172,037,965 (GRCm39) probably benign Het
Cimap2 C A 4: 106,467,612 (GRCm39) M341I probably benign Het
Cltc A T 11: 86,617,196 (GRCm39) M351K probably benign Het
Cnp A G 11: 100,469,877 (GRCm39) E271G possibly damaging Het
Col22a1 T C 15: 71,845,544 (GRCm39) D406G possibly damaging Het
Cylc2 T C 4: 51,228,279 (GRCm39) S117P probably benign Het
Cyp2b13 T C 7: 25,761,072 (GRCm39) L43P probably damaging Het
Cyp3a16 A G 5: 145,373,267 (GRCm39) V500A probably benign Het
Dclk2 T C 3: 86,743,683 (GRCm39) D262G probably damaging Het
Dcun1d3 A C 7: 119,458,742 (GRCm39) Y98D probably damaging Het
Ddx39b A G 17: 35,472,464 (GRCm39) *429W probably null Het
Dennd5b T C 6: 148,908,335 (GRCm39) N986S probably damaging Het
Dipk1a T C 5: 108,057,982 (GRCm39) probably null Het
Dusp9 G A X: 72,684,378 (GRCm39) R182Q probably benign Het
Ecpas A T 4: 58,834,523 (GRCm39) I785N possibly damaging Het
Edil3 A G 13: 89,437,589 (GRCm39) K397E probably damaging Het
Ehd1 T C 19: 6,326,994 (GRCm39) probably benign Het
Fam13a A T 6: 58,964,152 (GRCm39) H93Q probably benign Het
Farp1 T C 14: 121,513,716 (GRCm39) I837T possibly damaging Het
Gadl1 G A 9: 115,770,408 (GRCm39) E74K probably damaging Het
Gnpnat1 A G 14: 45,618,436 (GRCm39) V122A probably damaging Het
Hdac10 C T 15: 89,011,036 (GRCm39) probably benign Het
Heatr5b T C 17: 79,128,130 (GRCm39) S502G possibly damaging Het
Hr C A 14: 70,801,013 (GRCm39) A695E probably damaging Het
Ift80 A T 3: 68,825,870 (GRCm39) I490N possibly damaging Het
Ipo11 A G 13: 106,970,692 (GRCm39) probably benign Het
Iqch T G 9: 63,432,195 (GRCm39) Y400S probably damaging Het
Jag2 C T 12: 112,877,266 (GRCm39) D702N probably benign Het
Kiss1r T A 10: 79,757,624 (GRCm39) L326Q probably damaging Het
Lrrc42 A T 4: 107,104,746 (GRCm39) I73N probably damaging Het
Lrrc55 C T 2: 85,026,880 (GRCm39) G48D possibly damaging Het
Lrrk2 T C 15: 91,649,884 (GRCm39) S1674P probably damaging Het
Mctp2 A G 7: 71,739,942 (GRCm39) L816P probably damaging Het
Mipol1 A T 12: 57,352,918 (GRCm39) T86S probably benign Het
Mkrn3 C T 7: 62,069,452 (GRCm39) R113H probably damaging Het
Mmp1b A G 9: 7,370,849 (GRCm39) V302A probably benign Het
Msc A T 1: 14,826,053 (GRCm39) probably null Het
Msmo1 C A 8: 65,180,888 (GRCm39) V9L probably benign Het
Nbeal2 G A 9: 110,461,072 (GRCm39) R1630C probably damaging Het
Nlgn1 C T 3: 26,187,850 (GRCm39) V12I possibly damaging Het
Npas3 T C 12: 54,108,915 (GRCm39) probably null Het
Nr2e3 A G 9: 59,856,355 (GRCm39) probably benign Het
Oca2 C T 7: 55,978,560 (GRCm39) A576V probably benign Het
Or5b21 T A 19: 12,839,596 (GRCm39) C152* probably null Het
Or6d12 T C 6: 116,493,409 (GRCm39) Y224H probably damaging Het
Or6z7 T C 7: 6,484,045 (GRCm39) T37A probably benign Het
Parp6 A G 9: 59,548,383 (GRCm39) probably null Het
Pate13 T A 9: 35,820,287 (GRCm39) C4S probably damaging Het
Phlpp1 A T 1: 106,267,231 (GRCm39) M715L probably benign Het
Pi4k2a G A 19: 42,101,544 (GRCm39) probably null Het
Pik3ap1 A G 19: 41,316,348 (GRCm39) S305P probably damaging Het
Plcg2 G A 8: 118,231,054 (GRCm39) M45I probably benign Het
Ppm1m A T 9: 106,073,601 (GRCm39) L317H probably damaging Het
Ppp1r21 T G 17: 88,866,227 (GRCm39) M341R probably benign Het
Prdx3 A G 19: 60,853,674 (GRCm39) V217A possibly damaging Het
Ptk2b A G 14: 66,400,496 (GRCm39) V773A possibly damaging Het
Raly T C 2: 154,699,376 (GRCm39) V60A probably damaging Het
Reps1 A G 10: 17,990,148 (GRCm39) D420G probably damaging Het
Rev1 A T 1: 38,118,337 (GRCm39) probably benign Het
Rgs2 T G 1: 143,878,650 (GRCm39) probably benign Het
Rlf G T 4: 121,007,798 (GRCm39) T394K probably benign Het
Rptn A T 3: 93,304,792 (GRCm39) R708S possibly damaging Het
Sec23b T A 2: 144,414,494 (GRCm39) M402K probably benign Het
Skic2 A G 17: 35,068,922 (GRCm39) C26R probably damaging Het
Slx9 T C 10: 77,325,860 (GRCm39) M170V possibly damaging Het
Smpd4 A G 16: 17,459,992 (GRCm39) probably benign Het
Synj2 A G 17: 6,063,813 (GRCm39) E434G probably damaging Het
Tatdn2 T A 6: 113,684,326 (GRCm39) F64I probably benign Het
Tex21 A C 12: 76,263,860 (GRCm39) H177Q probably benign Het
Tln1 T A 4: 43,535,954 (GRCm39) Q2077L probably null Het
Tnrc6c T C 11: 117,611,797 (GRCm39) V145A probably benign Het
Ttn C T 2: 76,616,936 (GRCm39) probably benign Het
Uggt2 A G 14: 119,269,670 (GRCm39) F954S possibly damaging Het
Ugt2a1 A G 5: 87,634,083 (GRCm39) S175P probably damaging Het
Vcl A G 14: 21,035,820 (GRCm39) probably null Het
Vegfa A T 17: 46,336,176 (GRCm39) probably benign Het
Vmn2r68 G A 7: 84,882,769 (GRCm39) Q328* probably null Het
Vmn2r7 A G 3: 64,626,864 (GRCm39) Y142H probably benign Het
Wdr17 C T 8: 55,134,434 (GRCm39) G349R probably damaging Het
Ybx3 G T 6: 131,347,290 (GRCm39) R282S probably damaging Het
Zfp566 T C 7: 29,777,194 (GRCm39) H329R probably damaging Het
Zfp786 T C 6: 47,797,868 (GRCm39) I357V probably benign Het
Zfr2 C A 10: 81,087,083 (GRCm39) probably null Het
Other mutations in Fbxl5
AlleleSourceChrCoordTypePredicted EffectPPH 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
R1921:Fbxl5 UTSW 5 43,922,832 (GRCm39) missense probably benign 0.16
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
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'- TGGTCAAACCCTCAAAGTTTCC -3'
(R):5'- AAGGAATCGACTTCAGGCAC -3'

Sequencing Primer
(F):5'- GGCTGTCACTATTTGTCTAAAAAGGC -3'
(R):5'- AGGCACTGGCTTTTACTCG -3'
Posted On 2015-10-08