Incidental Mutation 'F5493:Fmo2'
ID565
Institutional Source Beutler Lab
Gene Symbol Fmo2
Ensembl Gene ENSMUSG00000040170
Gene Nameflavin containing monooxygenase 2
Synonyms2310008D08Rik, 2310042I22Rik
Accession Numbers

Genbank: NM_018881

Is this an essential gene? Probably non essential (E-score: 0.065) question?
Stock #F5493 (G1)
Quality Score
Status Validated
Chromosome1
Chromosomal Location162874317-162898726 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) C to A at 162880532 bp
ZygosityHeterozygous
Amino Acid Change Valine to Leucine at position 345 (V345L)
Ref Sequence ENSEMBL: ENSMUSP00000107135 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000045902] [ENSMUST00000111510]
Predicted Effect probably benign
Transcript: ENSMUST00000045902
AA Change: V345L

PolyPhen 2 Score 0.411 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000044405
Gene: ENSMUSG00000040170
AA Change: V345L

DomainStartEndE-ValueType
Pfam:FMO-like 2 533 8.7e-296 PFAM
Pfam:Pyr_redox_2 3 230 6.4e-12 PFAM
Pfam:Pyr_redox_3 6 220 4.4e-10 PFAM
Pfam:K_oxygenase 69 233 2.2e-11 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000111510
AA Change: V345L

PolyPhen 2 Score 0.411 (Sensitivity: 0.89; Specificity: 0.90)
SMART Domains Protein: ENSMUSP00000107135
Gene: ENSMUSG00000040170
AA Change: V345L

DomainStartEndE-ValueType
Pfam:FMO-like 2 533 8.7e-296 PFAM
Pfam:Pyr_redox_2 4 446 1.3e-6 PFAM
Pfam:Pyr_redox_3 6 220 8e-17 PFAM
Pfam:NAD_binding_8 7 72 4.3e-6 PFAM
Pfam:K_oxygenase 78 333 1.3e-12 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000194061
Predicted Effect noncoding transcript
Transcript: ENSMUST00000194197
Meta Mutation Damage Score 0.1198 question?
Coding Region Coverage
  • 1x: 76.6%
  • 3x: 51.4%
Het Detection Efficiency27.8%
Validation Efficiency 67% (74/111)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a flavin-containing monooxygenase family member. It is an NADPH-dependent enzyme that catalyzes the N-oxidation of some primary alkylamines through an N-hydroxylamine intermediate. However, some human populations contain an allele (FMO2*2A) with a premature stop codon, resulting in a protein that is C-terminally-truncated, has no catalytic activity, and is likely degraded rapidly. This gene is found in a cluster with other related family members on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]
Allele List at MGI
Other mutations in this stock
Total: 10 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Cars T A 7: 143,569,871 T448S probably damaging Het
Cdca2 T A 14: 67,677,692 N706I probably damaging Het
Fat1 A G 8: 45,025,480 E2521G probably damaging Het
Frrs1l T C 4: 56,968,293 M160V probably benign Het
Nckap5 A T 1: 126,025,827 M996K probably benign Het
Nlrp4d A T 7: 10,381,084 D568E possibly damaging Het
Pex1 T G 5: 3,635,912 probably null Het
Ptprd A G 4: 76,084,408 L17P probably damaging Het
Tnfsf13b T A 8: 10,006,916 V25E probably damaging Het
Zfp386 T C 12: 116,060,302 Y512H probably damaging Het
Other mutations in Fmo2
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00715:Fmo2 APN 1 162888713 nonsense probably null
IGL01299:Fmo2 APN 1 162878030 missense probably benign
IGL02617:Fmo2 APN 1 162876921 missense probably damaging 1.00
IGL02994:Fmo2 APN 1 162880620 missense probably damaging 1.00
IGL03270:Fmo2 APN 1 162882026 missense probably damaging 1.00
R0058:Fmo2 UTSW 1 162886324 missense probably benign 0.38
R0058:Fmo2 UTSW 1 162886324 missense probably benign 0.38
R0501:Fmo2 UTSW 1 162876928 missense probably benign 0.00
R0658:Fmo2 UTSW 1 162876774 missense possibly damaging 0.57
R0800:Fmo2 UTSW 1 162876814 missense probably benign 0.00
R2223:Fmo2 UTSW 1 162898244 missense probably damaging 1.00
R4360:Fmo2 UTSW 1 162882014 missense probably damaging 0.99
R4523:Fmo2 UTSW 1 162887708 missense probably benign 0.44
R4755:Fmo2 UTSW 1 162888805 missense probably damaging 1.00
R6087:Fmo2 UTSW 1 162880433 missense probably benign 0.45
R6219:Fmo2 UTSW 1 162880516 missense probably damaging 0.97
R6668:Fmo2 UTSW 1 162877048 missense probably benign 0.15
R7042:Fmo2 UTSW 1 162880657 missense probably damaging 1.00
R7291:Fmo2 UTSW 1 162887702 missense probably benign 0.06
R7560:Fmo2 UTSW 1 162888749 missense probably damaging 1.00
R7580:Fmo2 UTSW 1 162877044 missense possibly damaging 0.46
R7657:Fmo2 UTSW 1 162888844 missense probably damaging 1.00
Z1176:Fmo2 UTSW 1 162887598 missense probably benign 0.01
Z1176:Fmo2 UTSW 1 162898274 missense probably damaging 1.00
Nature of Mutation

DNA sequencing using the SOLiD technique identified a G to T transition at position 1080 of the Fmo2 transcript in exon 7 of 9 total exons. Multiple transcripts of the Fmo2 gene are displayed on Ensembl and Vega.  The mutated nucleotide causes a valine to leucine substitution at amino acid 345 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (see related file).

Protein Function and Prediction

The Fmo2 gene encodes a 535 amino acid flavin-containing monooxygenase.  These enzymes are NADPH-dependent flavoenzymes that catalyze the oxidation of heteroatom centers in numerous drugs and xenobiotics.  FAD binding occurs at amino acids 9-14. NADP binding occurs at amino acids 191-196 (Uniprot Q8K2I3). The most common allele of this gene in humans encodes a truncated, inactive protein. This allele is not present in closely related primates.

 

The V345L change is predicted to be benign by the PolyPhen program.

Posted On2010-11-29