Incidental Mutation 'R4566:Fbxw4'
ID 343332
Institutional Source Beutler Lab
Gene Symbol Fbxw4
Ensembl Gene ENSMUSG00000040913
Gene Name F-box and WD-40 domain protein 4
Synonyms dactylin, Fbw4, dactylyn
Accession Numbers
Essential gene? Possibly non essential (E-score: 0.450) question?
Stock # R4566 (G1)
Quality Score 225
Status Not validated
Chromosome 19
Chromosomal Location 45566693-45648751 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 45580225 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Valine to Alanine at position 258 (V258A)
Ref Sequence ENSEMBL: ENSMUSP00000036505 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000046869] [ENSMUST00000160003] [ENSMUST00000160018] [ENSMUST00000160438] [ENSMUST00000162433] [ENSMUST00000162879]
AlphaFold Q9JMJ2
Predicted Effect probably benign
Transcript: ENSMUST00000046869
AA Change: V258A

PolyPhen 2 Score 0.244 (Sensitivity: 0.91; Specificity: 0.88)
SMART Domains Protein: ENSMUSP00000036505
Gene: ENSMUSG00000040913
AA Change: V258A

DomainStartEndE-ValueType
low complexity region 2 22 N/A INTRINSIC
FBOX 29 69 1.47e-2 SMART
WD40 150 187 3.45e-1 SMART
WD40 189 226 2.24e-2 SMART
WD40 232 274 8.91e-1 SMART
WD40 277 318 5.52e0 SMART
WD40 323 363 1.67e-1 SMART
Blast:WD40 366 406 1e-10 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000160003
SMART Domains Protein: ENSMUSP00000124604
Gene: ENSMUSG00000040913

DomainStartEndE-ValueType
Blast:WD40 1 36 2e-20 BLAST
SCOP:d1fwxa2 8 62 4e-7 SMART
Blast:WD40 39 79 1e-12 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000160018
SMART Domains Protein: ENSMUSP00000125641
Gene: ENSMUSG00000040913

DomainStartEndE-ValueType
Blast:WD40 1 21 8e-8 BLAST
Predicted Effect silent
Transcript: ENSMUST00000160438
SMART Domains Protein: ENSMUSP00000125136
Gene: ENSMUSG00000040913

DomainStartEndE-ValueType
signal peptide 1 24 N/A INTRINSIC
WD40 52 93 5.52e0 SMART
WD40 98 138 1.67e-1 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000160718
Predicted Effect noncoding transcript
Transcript: ENSMUST00000161556
Predicted Effect probably benign
Transcript: ENSMUST00000162433
SMART Domains Protein: ENSMUSP00000124998
Gene: ENSMUSG00000040913

DomainStartEndE-ValueType
Blast:WD40 1 21 5e-7 BLAST
WD40 26 66 1.67e-1 SMART
Blast:WD40 69 109 3e-12 BLAST
Predicted Effect probably benign
Transcript: ENSMUST00000162879
SMART Domains Protein: ENSMUSP00000124675
Gene: ENSMUSG00000040913

DomainStartEndE-ValueType
Blast:WD40 1 21 4e-7 BLAST
WD40 26 66 1.67e-1 SMART
Blast:WD40 69 102 8e-9 BLAST
Coding Region Coverage
  • 1x: 99.2%
  • 3x: 98.6%
  • 10x: 97.2%
  • 20x: 95.0%
Validation Efficiency
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene is a member of the F-box/WD-40 gene family, which recruit specific target proteins through their WD-40 protein-protein binding domains for ubiquitin mediated degradation. In mouse, a highly similar protein is thought to be responsible for maintaining the apical ectodermal ridge of developing limb buds; disruption of the mouse gene results in the absence of central digits, underdeveloped or absent metacarpal/metatarsal bones and syndactyly. This phenotype is remarkably similar to split hand-split foot malformation in humans, a clinically heterogeneous condition with a variety of modes of transmission. An autosomal recessive form has been mapped to the chromosomal region where this gene is located, and complex rearrangements involving duplications of this gene and others have been associated with the condition. A pseudogene of this locus has been mapped to one of the introns of the BCR gene on chromosome 22. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygotes for a spontaneous null mutation lack feet except for a single fused digit and die prenatally. Heterozygotes, in the presence of a recessive modifying allele, show loss of digits, frequently with fused metatarsal and metacarpal bones. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 21 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adgrv1 T C 13: 81,567,927 (GRCm39) E5082G probably damaging Het
Apol7a A T 15: 77,273,951 (GRCm39) Y170* probably null Het
Cfhr1 T A 1: 139,481,386 (GRCm39) I165F possibly damaging Het
Dnah8 G A 17: 30,967,542 (GRCm39) D2585N probably benign Het
Espnl C A 1: 91,272,301 (GRCm39) P510T possibly damaging Het
Foxq1 T C 13: 31,743,471 (GRCm39) M191T probably benign Het
Gabrg1 A T 5: 70,999,484 (GRCm39) L22I probably benign Het
Limk1 A G 5: 134,715,537 (GRCm39) L38P probably benign Het
Mfhas1 C T 8: 36,058,203 (GRCm39) R893C probably damaging Het
Mug2 G A 6: 122,056,597 (GRCm39) V1181I probably benign Het
Or52ac1 A T 7: 104,245,823 (GRCm39) C188* probably null Het
Pithd1 A G 4: 135,704,548 (GRCm39) V56A probably damaging Het
Plxna4 T C 6: 32,494,338 (GRCm39) K93E probably benign Het
Ppp2cb T C 8: 34,100,723 (GRCm39) V48A possibly damaging Het
Rasl2-9 AGG A 7: 5,128,374 (GRCm39) probably null Het
Rrs1 T C 1: 9,616,452 (GRCm39) F235S probably damaging Het
Rtl1 G A 12: 109,559,293 (GRCm39) L849F probably damaging Het
Slc5a9 C A 4: 111,748,941 (GRCm39) probably null Het
Trps1 A G 15: 50,695,074 (GRCm39) V116A probably damaging Het
Vmn2r51 C T 7: 9,836,341 (GRCm39) E147K probably benign Het
Yy1 T A 12: 108,778,889 (GRCm39) I296K probably damaging Het
Other mutations in Fbxw4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL01120:Fbxw4 APN 19 45,628,955 (GRCm39) missense probably benign 0.09
IGL03089:Fbxw4 APN 19 45,580,160 (GRCm39) splice site probably benign
R5827:Fbxw4 UTSW 19 45,568,096 (GRCm39) missense probably benign 0.05
R6175:Fbxw4 UTSW 19 45,624,766 (GRCm39) missense probably benign 0.00
R6829:Fbxw4 UTSW 19 45,624,813 (GRCm39) missense possibly damaging 0.46
R6862:Fbxw4 UTSW 19 45,571,187 (GRCm39) missense probably benign 0.01
R7528:Fbxw4 UTSW 19 45,648,449 (GRCm39) missense unknown
R9015:Fbxw4 UTSW 19 45,624,874 (GRCm39) missense probably benign 0.03
Predicted Primers PCR Primer
(F):5'- ATGCACTGCAGCTGTTGGTG -3'
(R):5'- TTCGCACCAAGTTGTCTTAGAG -3'

Sequencing Primer
(F):5'- GAGGTGTGATTTCTCCCGC -3'
(R):5'- CGCACCAAGTTGTCTTAGAGATTTC -3'
Posted On 2015-09-24