FMO3

Chr 1AR

flavin containing dimethylaniline monoxygenase 3

Also known as: FMOII, TMAU, dJ127D3.1

Flavin-containing monooxygenases (FMO) are an important class of drug-metabolizing enzymes that catalyze the NADPH-dependent oxygenation of various nitrogen-,sulfur-, and phosphorous-containing xenobiotics such as therapeutic drugs, dietary compounds, pesticides, and other foreign compounds. The human FMO gene family is composed of 5 genes and multiple pseudogenes. FMO members have distinct developmental- and tissue-specific expression patterns. The expression of this FMO3 gene, the major FMO expressed in adult liver, can vary up to 20-fold between individuals. This inter-individual variation in FMO3 expression levels is likely to have significant effects on the rate at which xenobiotics are metabolised and, therefore, is of considerable interest to the pharmaceutical industry. This transmembrane protein localizes to the endoplasmic reticulum of many tissues. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. Mutations in this gene cause the disorder trimethylaminuria (TMAu) which is characterized by the accumulation and excretion of unmetabolized trimethylamine and a distinctive body odor. In healthy individuals, trimethylamine is primarily converted to the non odorous trimethylamine N-oxide.[provided by RefSeq, Jan 2016]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

TrimethylaminuriaMIM #602079
AR

Clinical highlights

Gene-disease validity (ClinGen)
trimethylaminuria · ARDefinitivesufficient evidence for diagnostic panels
0
Active trials
63
Pubs (1 yr)
P/LP submissions
P/LP missense
1.58
LOEUF
Multiple*
Mechanism· predicted
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
1.58LOEUF
pLI 0.000
Z-score -0.46
OE 1.11 (0.791.58)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.16Z-score
OE missense 1.03 (0.931.13)
300 obs / 292.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?1.11 (0.791.58)
00.351.4
Missense OE?1.03 (0.931.13)
00.61.4
Synonymous OE?0.87
01.21.6
LoF obs/exp: 22 / 19.8Missense obs/exp: 300 / 292.1Syn Z: 1.08

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

FMO3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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