FMO5

Chr 1

flavin containing dimethylaniline monoxygenase 5

Also known as: hBVMO1

The FMO5 protein functions as a Baeyer-Villiger monooxygenase that catalyzes oxygen insertion into carbon-carbon bonds adjacent to carbonyls, converting ketones to esters, and also modulates cholesterol biosynthesis and glucose homeostasis. While other flavin-containing monooxygenases cause trimethylaminuria when mutated, no specific genetic disorders have been definitively associated with FMO5 mutations despite its metabolic functions. The gene shows high tolerance to loss-of-function variants (LOEUF 1.448), suggesting that complete loss of FMO5 function may be well-tolerated in humans.

GeneReviewsOMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.45
Clinical SummaryFMO5
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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.
📖
GeneReview available — FMO5
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.45LOEUF
pLI 0.000
Z-score -0.06
OE 1.01 (0.721.45)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.63Z-score
OE missense 1.10 (1.011.21)
319 obs / 288.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.01 (0.721.45)
00.351.4
Missense OE1.10 (1.011.21)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 22 / 21.7Missense obs/exp: 319 / 288.7Syn Z: 0.73
DN
0.73top 25%
GOF
0.72top 25%
LOF
0.2776th %ile

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

DNprediction above median
GOFprediction 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

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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