FMO1

Chr 1

flavin containing dimethylaniline monoxygenase 1

NCBI Gene: 2326 ENSG00000010932 OMIM: 136130

FMO1 encodes a flavin-containing monooxygenase that catalyzes the oxidation of nitrogen- and sulfur-containing compounds including xenobiotics, and produces taurine from hypotaurine for cellular osmoregulation and cytoprotection. FMO1 is primarily expressed in fetal liver and differs from FMO3, which when mutated causes trimethylaminuria (fish odor syndrome) through impaired trimethylamine metabolism. The gene shows very low constraint against loss-of-function variants, and no definitive human disease associations have been established for FMO1 mutations.

OMIM ResearchSummary from RefSeq, UniProt

Metabolic N-oxidation of the diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in man resulting in a small subpopulation with reduced TMA N-oxidation capacity resulting in fish odor syndrome Trimethylaminuria. Three forms of the enzyme, FMO1 found in fetal liver, FMO2 found in adult liver, and FMO3 are encoded by genes clustered in the 1q23-q25 region. Flavin-containing monooxygenases are NADPH-dependent flavoenzymes that catalyzes the oxidation of soft nucleophilic heteroatom centers in drugs, pesticides, and xenobiotics. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.09

Clinical Summary— FMO1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

61 VUS of 77 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.09LOEUF

pLI 0.000

Z-score 1.20

OE 0.74 (0.52–1.09)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.05Z-score

OE missense 0.82 (0.74–0.92)

235 obs / 285.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.52–1.09)

0≤0.351.4

Missense OE?0.82 (0.74–0.92)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 19 / 25.5Missense obs/exp: 235 / 285.0Syn Z: -0.75

This gene — mechanism propensity

0.7131th %ile

GOF

0.72top 25%

LOF

0.2484th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

77 submitted variants in ClinVar

ClinVar

Classification Summary

VUS61

Likely Benign6

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	61	0	0	61
Likely Benign	5	0	1	6
Benign	2	1	0	3
Total	68	1	1	70

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

26 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap FMO1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →