FMO3 V257M - GET-Evidence

Curation:
Currentness:

FMO3 V257M

(FMO3 Val257Met)


Short summary

This common variant (HapMap allele frequency of 9.2%) appears to have no functional effect. OMIM has recorded it as having been seen homozygously in an individual with Trimethylaminuria, but Treacy et al. 1998 conclude it is a polymorphism.

Variant evidence
Computational 2

Amino acid change is not disruptive, Polyphen2 predicts benign effect.

Functional -
Case/Control 1

High allele frequency in the population supports no significant pathogenic effect.

See Treacy EP et al. 1998 (9536088).

Familial
 
Clinical importance
Severity -
Treatability -
Penetrance -
 

Impact

Low clinical importance, Uncertain benign

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • A @ chr1:171080080: 5.7% (614/10758) in EVS
  • A @ chr1:169346703: 10.2% (13/128) in GET-Evidence
  • Frequency shown in summary reports: 5.7% (614/10758)

Publications
 

Treacy EP, Akerman BR, Chow LM, Youil R, Bibeau C, Lin J, Bruce AG, Knight M, Danks DM, Cashman JR, Forrest SM. Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication. Hum Mol Genet. 1998 May;7(5):839-45. PubMed PMID: 9536088.

From the paper: “The substitution V257M was observed in five of 40 normal control Australian chromosomes, suggesting that this substitution may represent a prevalent polymorphism.”

Genomes
 

hu0D879F - CGI sample GS00253-DNA_G01_200_37
het A @ chr1:171080080

 

 

hu44DCFF - CGI sample GS01669-DNA_C07 from PGP sample 74521372
het A @ chr1:171080080

 

huD81F3D - CGI sample GS01173-DNA_D06 from PGP sample 69488604
het A @ chr1:171080080

 

huE80E3D - CGI sample GS00253-DNA_D01_200_37
het A @ chr1:171080080

 

GS07357 - var-GS07357-1100-36-ASM
het A @ chr1:169346704

 

GS10851 - var-GS10851-1100-36-ASM
het A @ chr1:169346704

 

GS18537 - var-GS18537-1100-36-ASM
het A @ chr1:169346704

 

GS18558 - var-GS18558-1100-36-ASM
het A @ chr1:169346704

 

GS18942 - var-GS18942-1100-36-ASM
het A @ chr1:169346704

 

GS19017 - var-GS19017-1100-36-ASM
het A @ chr1:169346704

 

GS19649 - var-GS19649-1100-36-ASM
het A @ chr1:169346704

 

NA12878

 

Other external references
 

    dbSNP
  • rs1736557
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0 (benign)
    Web search results (71 hits -- see all)
  • BioMed Central | Full text | Polymorphisms of the Flavin ...
    FMO3 genotypes (E158K, V257M, E308G) were determined in 387 healthy subjects ... common polymorphisms of the FMO3 gene (E158K, V257M, E308G) in a North American ...
    www.biomedcentral.com/1471-2350/6/41
  • Homo sapiens FMO3 Allelic Variant Database - Table of All ...
    V257M. Exon. 6. 769. 257. Transition. 0. G. A. GTG. ATG. Val. Met. Missense. Unchanged. Unchanged ... Vmax/Km of mutant-type FMO3 was about 5 times < than wt FMO3 ...
    human-fmo3.biochem.ucl.ac.uk/Human_FMO3/Tables/tableall.html
  • Flavin monooxygenase 3 (FMO3) polymorphism in a white ...
    FMO3 polymorphisms M66I, P153L, E158K, V257M, E305X, E308G, and R492W ... Subjects with these frequent variants of FMO3, however, did not differ in clozapine ...
    www.ncbi.nlm.nih.gov/pubmed/10546928
  • Mutations of the flavin-containing monooxygenase gene (FMO3 ...
    ( A) Analysis of the FMO3 exon 6 polymorphism V257M on an 8% polyacrylamide gel. ... The substitution V257M was observed in five of 40 normal control ...
    hmg.oxfordjournals.org/cgi/content/full/7/5/839
  • BMC Medical Genetics
    FMO3 gene confer an increased risk for elevated blood pressure and/or essential ... Methods: FMO3 genotypes (E158K, V257M, E308G) were determined in 387 healthy subjects with ...
    www.biomedcentral.com/content/pdf/1471-2350-6-41.pdf
  • Functional Characterization of Genetic Variants of Human FMO3 ...
    FMO3 is a major form of the enzyme present in adult human liver, ... That the Km for the V257M mutant with the largest substrate used, benzydamine, ...
    www.ncbi.nlm.nih.gov/pmc/articles/PMC2039921/?tool=pmcentrez
  • Directory of open access journals
    FMO3 genotypes (E158K, V257M, E308G) were determined in 387 healthy subjects ... suggest that the variants in the FMO3 gene do not predispose to essential ...
    www.doaj.org/doaj?func=abstract&id=126557&recNo=41&toc=1
  • <!DOCTYPE xhtml PUBLIC "-/W3C/DTD XHTML 1.0 Transitional/EN ...
    ... The human FMO3 alleleic variant database|18 Accession Number|Systematic Name ... 769G&gt;A|V257M|[]|[]|[]|Exon|6|769|257|[]|Transition|0|[]|G|A|[]|GTG|ATG|Val ...
    human-fmo3.biochem.ucl.ac.uk/Human_FMO3/.../Human_FMO3.txt
  • PowerPoint
    Polymorphic FMO3 proteins can exhibit reduced enzymatic activity for ... FMO3 polymorphisms E158K and E308G have been shown to occur more frequently in ...
    oregonstate.edu/dept/biochem/hhmi/.../2008/Bemer.ppt

Other in silico analyses
 

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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