Incidental Mutation 'P0007:Fbxo7'
ID 7594
Institutional Source Beutler Lab
Gene Symbol Fbxo7
Ensembl Gene ENSMUSG00000001786
Gene Name F-box protein 7
Synonyms 2410015K21Rik, A230052G17Rik
MMRRC Submission 038263-MU
Accession Numbers
Essential gene? Non essential (E-score: 0.000) question?
Stock # P0007 (G1)
Quality Score
Status Validated
Chromosome 10
Chromosomal Location 85857836-85887737 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 85869157 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Serine to Proline at position 204 (S204P)
Ref Sequence ENSEMBL: ENSMUSP00000113222 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000001837] [ENSMUST00000117597] [ENSMUST00000120344] [ENSMUST00000130320] [ENSMUST00000147168]
AlphaFold Q3U7U3
Predicted Effect probably benign
Transcript: ENSMUST00000001837
SMART Domains Protein: ENSMUSP00000001837
Gene: ENSMUSG00000001786

DomainStartEndE-ValueType
Blast:UBQ 1 40 7e-10 BLAST
Predicted Effect possibly damaging
Transcript: ENSMUST00000117597
AA Change: S202P

PolyPhen 2 Score 0.794 (Sensitivity: 0.85; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000113263
Gene: ENSMUSG00000001786
AA Change: S202P

DomainStartEndE-ValueType
Pfam:PI31_Prot_N 101 245 9.6e-31 PFAM
Pfam:F-box 250 297 2.7e-6 PFAM
Pfam:F-box-like 252 298 7.2e-8 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000120344
AA Change: S204P

PolyPhen 2 Score 0.948 (Sensitivity: 0.79; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000113222
Gene: ENSMUSG00000001786
AA Change: S204P

DomainStartEndE-ValueType
Pfam:PI31_Prot_N 103 247 4.8e-31 PFAM
Pfam:F-box 252 299 1.8e-6 PFAM
Pfam:F-box-like 254 300 5.1e-8 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000130320
AA Change: S283P

PolyPhen 2 Score 0.101 (Sensitivity: 0.93; Specificity: 0.86)
SMART Domains Protein: ENSMUSP00000120840
Gene: ENSMUSG00000001786
AA Change: S283P

DomainStartEndE-ValueType
SCOP:d1euvb_ 1 78 7e-6 SMART
Blast:UBQ 1 79 6e-30 BLAST
Pfam:PI31_Prot_N 188 323 4.7e-20 PFAM
Pfam:F-box 331 378 9.7e-6 PFAM
Pfam:F-box-like 333 379 9.3e-8 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000134490
Predicted Effect probably benign
Transcript: ENSMUST00000147168
Meta Mutation Damage Score 0.1389 question?
Coding Region Coverage
  • 1x: 85.2%
  • 3x: 80.2%
  • 10x: 65.3%
  • 20x: 42.8%
Validation Efficiency 94% (102/109)
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 the 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 Fbxs class and it may play a role in regulation of hematopoiesis. Alternatively spliced transcript variants of this gene have been identified with the full-length natures of only some variants being determined. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit increased pro-B cell numbers and increased erythroid progenitor cell number. [provided by MGI curators]
Allele List at MGI

All alleles(7) : Targeted(4) Gene trapped(3)
Other mutations in this stock
Total: 8 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adamts6 A G 13: 104,433,999 (GRCm39) T143A possibly damaging Het
Cfap74 T A 4: 155,506,685 (GRCm39) S139T possibly damaging Het
Itga2 A T 13: 115,002,735 (GRCm39) I585N probably damaging Het
Lgi3 A G 14: 70,774,152 (GRCm39) Y442C probably damaging Het
Magi1 A G 6: 93,722,969 (GRCm39) I530T probably damaging Het
Med12l T C 3: 58,998,816 (GRCm39) probably benign Het
Nbeal1 A G 1: 60,358,847 (GRCm39) I1176M probably damaging Het
Ostn G T 16: 27,143,279 (GRCm39) G36* probably null Het
Other mutations in Fbxo7
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00519:Fbxo7 APN 10 85,864,928 (GRCm39) missense probably damaging 0.98
IGL01483:Fbxo7 APN 10 85,880,445 (GRCm39) missense probably damaging 1.00
IGL02502:Fbxo7 APN 10 85,869,161 (GRCm39) missense probably damaging 1.00
IGL02712:Fbxo7 APN 10 85,860,302 (GRCm39) missense possibly damaging 0.75
R0410:Fbxo7 UTSW 10 85,865,102 (GRCm39) critical splice donor site probably null
R4119:Fbxo7 UTSW 10 85,857,759 (GRCm39) unclassified probably benign
R4604:Fbxo7 UTSW 10 85,882,666 (GRCm39) missense probably damaging 1.00
R4884:Fbxo7 UTSW 10 85,865,014 (GRCm39) missense probably damaging 0.99
R5088:Fbxo7 UTSW 10 85,857,784 (GRCm39) unclassified probably benign
R5286:Fbxo7 UTSW 10 85,857,954 (GRCm39) missense probably damaging 1.00
R5387:Fbxo7 UTSW 10 85,860,518 (GRCm39) missense probably benign 0.01
R5451:Fbxo7 UTSW 10 85,864,901 (GRCm39) missense probably benign 0.01
R5491:Fbxo7 UTSW 10 85,883,890 (GRCm39) missense probably damaging 1.00
R5542:Fbxo7 UTSW 10 85,869,149 (GRCm39) missense probably benign 0.00
R5647:Fbxo7 UTSW 10 85,864,974 (GRCm39) missense probably damaging 0.98
R6027:Fbxo7 UTSW 10 85,883,950 (GRCm39) missense probably damaging 1.00
R6152:Fbxo7 UTSW 10 85,860,560 (GRCm39) missense probably benign 0.01
R6280:Fbxo7 UTSW 10 85,864,969 (GRCm39) missense probably benign 0.00
R6615:Fbxo7 UTSW 10 85,880,398 (GRCm39) missense possibly damaging 0.48
R7405:Fbxo7 UTSW 10 85,880,445 (GRCm39) missense probably damaging 1.00
R8785:Fbxo7 UTSW 10 85,860,410 (GRCm39) missense probably benign 0.02
R9743:Fbxo7 UTSW 10 85,883,773 (GRCm39) missense probably benign 0.06
Protein Function and Prediction

Fbox7 is an F-box protein and a component of SCF (Skp1, Cdc53/Cullin1, F-box protein) ubiquitin-ligase complexes (1).  F-box proteins, including Fbox7, are required for substrate recognition and recruitment in SCF-mediated proteolysis during processes such as cell cycle progression, transcription, and signal transduction (1).  Fbxo7 binds directly to p27 and Cdk6 (2).  Due to the ability of Fbxo7 to initiate Cdk6-dependent transformations, it has been proposed that Fbxo7 is an oncogene (3).
Background

Mutations in FBXO7 are known to cause Parkinson disease-15 [PARK15; OMIM: 260300; also known as the parkinsonian-pyramidal syndrome; (4;5)].  Clinical features included tremor, rigidity, akinesia, scissor gait, and hyperreflexia (5).

Fbxo7tm1a(EUCOMM)Hmgu/tm1a(EUCOMM)Hmgu; MGI:4434927

involves: C57BL/6N

Reduction in Fbxo7 expression results in increased proliferation, decreased cell size, and shortened G1 phase in pro-B cells (3).  Fbxo7 could not transform pro-B cells. Homozygous mice showed significantly increased pro-B cell and pro-erythroblast populations, consistent with Fbxo7 having an anti-proliferative function and/or a role in promoting maturation of precursor cells (3).
References
Posted On 2012-10-05
Science Writer Anne Murray