FMO5

Chr 1

flavin containing dimethylaniline monoxygenase 5

Also known as: hBVMO1

NCBI Gene: 2330ENSG00000131781UniProt: P49326

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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]

389
ClinVar variants
285
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— FMO5
🧬
Gene-Disease Validity (ClinGen)
congenital heart disease · ADDisputed

Disputed — evidence questions this relationship

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
285 Pathogenic / Likely Pathogenic· 96 VUS of 389 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.45LOEUF
pLI 0.000
Z-score -0.06
OE 1.01 (0.72–1.45)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.63Z-score
OE missense 1.10 (1.01–1.21)
319 obs / 288.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.01 (0.72–1.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.10 (1.01–1.21)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 22 / 21.7Missense obs/exp: 319 / 288.7Syn Z: 0.73

ClinVar Variant Classifications

389 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic247
Likely Pathogenic38
VUS96
Likely Benign7
Benign1
247
Pathogenic
38
Likely Pathogenic
96
VUS
7
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
247
0
247
Likely Pathogenic
0
0
38
0
38
VUS
0
86
10
0
96
Likely Benign
0
4
1
2
7
Benign
0
0
0
1
1
Total0902963389

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

View in ClinVar →

Protein Context — Lollipop Plot

FMO5 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — FMO5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Alcoholic fatty liver disease inhibited the co-expression of Fmo5 and PPARα to activate the NF-κB signaling pathway, thereby reducing liver injury via inducing gut microbiota disturbance.
Kong L et al.·J Exp Clin Cancer Res
2021
Clinical and metabolic phenotypes of Oxford Biobank subjects with variations in human flavin-containing monooxygenase 5 (FMO5).
Everett JR et al.·Metabolomics
2025
Drug metabolism by flavin-containing monooxygenases of human and mouse.
Phillips IR et al.·Expert Opin Drug Metab Toxicol
2017Review
Alternative processing events in human FMO genes.
Lattard V et al.·Mol Pharmacol
2004
COVID-19 severity gradient differentially dysregulates clinically relevant drug processing genes in nasopharyngeal swab samples.
Nwabufo CK et al.·Br J Clin Pharmacol
2024
Human gene copy number spectra analysis in congenital heart malformations.
Tomita-Mitchell A et al.·Physiol Genomics
2012
ACACB is a novel metabolism-related biomarker in the prediction of response to cetuximab therapy inmetastatic colorectal cancer.
Hong HJ et al.·Acta Biochim Biophys Sin (Shanghai)
2022
Regulation of FMO and PON detoxication systems in ALS human tissues.
Gagliardi S et al.·Neurotox Res
2013
Relationship between intratumoral expression of genes coding for xenobiotic-metabolizing enzymes and benefit from adjuvant tamoxifen in estrogen receptor alpha-positive postmenopausal breast carcinoma.
Bièche I et al.·Breast Cancer Res
2004
Metabolism of MRX-I, a novel antibacterial oxazolidinone, in humans: the oxidative ring opening of 2,3-Dihydropyridin-4-one catalyzed by non-P450 enzymes.
Meng J et al.·Drug Metab Dispos
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools