FMO3 codon 285 'silent mutation' : N285N

The DNA code for FMO3 is a 1596 nucleotide sequence (532 x 3).
This 532 x 3 nucleotide sequence creates a 532 amino acid sequence which creates the FMO3 protein.

codon	3-nucleotide code	resulting amino acid
283	gta	valine
284	ttt	phenylalinine
285	aac	asparagine (N)
286	gat	aspartic acid

Silent codons
Often a wrong nucleotide inserted can mean an incorrect amino acid created in the codon sequence.
FMO3 example : the common substitution at codon 158 results in E158K. It should be an E but came out a K (E stands for glutamic acid, K for lysine). Many people have this common mutation (estimates : 20-40% caucasians). It is currently regarded as 'benign' on it's own, but this may in future turn out to be wrong.

However, there are also substitution mutations where the wrong nucleotide is inserted but the resulting amino acid is correct. They are known as 'silent' (presumably as they are presumed not to affect function).

FMO3 example : N285N  (N = asparagine)

N285N turns out to be a seemingly common 'silent mutation' in ethnicities.

The question is, can 'silent' mutations affect function ?

At the moment, who knows ? . We have to assume mainstream experts will currently say no (?)

Common 'silent mutations' in the FMO3 gene coding region:
codon 147
codon 285 (N285N)

My own FMO3 'coding faults'
You can have faults in the coding part of your FMO3 DNA, but also faults in the non-coding parts (introns, promoter region, exon parts that do not code).
Ignoring my non-coding parts (as I don't have the info), I know the most important part : my own 532 coding sequence.
Note : Your 'coding region' can be 'normal' but you can still have TMAU due to faults in the non-coding region.

I carry 3 common SNP's :
E158K
N285N
E308G

FMO3 is about efficiency :
Bad analogy : 100m runner. Say a runner has small handicaps, e.g. broken arm. This may not effect his run much (say 94% normal). Whereas a broken leg may make the run 20% normal. It's the same idea with most FMO3 faults. They may affect function minimally, or you may have a few compounded small gene faults which may drag you down to 85% sometimes. FMO3 should be working at say 95%+.

So at the moment I am presuming my 'small faults' combine to affect FMO3 function either to a small % or perhaps intermittently. Personally I always feel lousy (e.g. migraine) and suspect it may be to do with FMO3 function as FMO3 is regarded as one of the group of heavy-duty 'detoxifier' enzymes (in the case of FMO3, to detoxify abundant small sulfides and amines of a certain structure). It seems not that much is known of the 'detoxifier enzymes', with the main group (the CYP450's) being identified as the main players, and FMO3 regarded as lesser players ... but perhaps this will later prove to be incorrect,

The main reason for the post was to point out the notion of 'silent' SNP's.

Commonality of N285N :
This paper from 2006 mentions N285N and it's commonality in some ethnicities.
2007 FMO3 paper :
Identification and Functional Analysis of Common Human Flavin-Containing Monooxygenase 3 Genetic Variants

Summary :
N285N silent mutation is currently regarded as having no effect on the efficiency of FMO3 enzyme function, and is quite common. It will most likely not be listed in a clinical FMO3 gene test as they tend to list only mutations they feel may have an affect. To see if you have N285N, you would need a copy of your full 532 codon FMO3 code (or at least, any variations from 'normal' listed).

What has this to do with systemic body odor ?
My own current belief is that FMO3 enzyme may be implicated in most cases of systemic body odor. SBO is not currently a properly documented disorder, with only TMAU being given as a diagnosis of the SBO concept ... perhaps a gross underdiagnosis.

Other links :
2006 paper : silent mutations
2014 article : silent mutations
Stanford 2015 article
Codon amino acid abbreviation code list
The main different types of mutations in a gene
wikipedia : FMO enzyme family

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By sysbodyodor

fmo3, FMO3 reference, systemic body odor, systemic malodor syndrome

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