FMO5
protein-codingflavin containing dimethylaniline monoxygenase 5, the group of Flavin containing monooxygenases
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~67.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005453
Submitter: ClinGen
*FMO5* was first reported in relation to congenital heart disease in 2012 (Tomita-Mitchell et al.; PMID: 22318994). Six multi-gene CNVs that have been reported in six probands in one publication (PMID: 22318994) are included in this curation, but not scored, due to extending beyond the *FMO5* coding region. In summary, the evidence supporting the relationship between *FMO5* and congenital heart disease has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role FMO5 plays in this disease. This classification was initially approved by the ClinGen Congenital Heart Disease GCEP on the meeting date 11/27/2023 (SOP Version 10). It was re-evaluated on 6/8/2026 (SOP Version 12). No new evidence was found. As a result of this reevaluation, the classification did not change.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FMO5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001461.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 1 | 4 | ||
| missense | 88 | 4 | 92 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 93 | 5 | 1 | 99 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001452.2 | 8 | MANE Select | |
| Ensembl | ENSP00000254090.4 | 8 | MANE Select | |
| RefSeq | NP_001138301.1 | 8 | Standard | |
| RefSeq | NP_001138302.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Drug metabolism - cytochrome P450 - Homo sapiens (human)
- Busulfan Pathway, Pharmacodynamics
- Catalytic cycle of mammalian Flavin-containing MonoOxygenases (FMOs)
- Metapathway biotransformation Phase I and II
- Selenoamino acid metabolism
Biological Process
- biological_process
- oxidation-reduction process
Molecular Function
- monooxygenase activity
- N,N-dimethylaniline monooxygenase activity
- flavin adenine dinucleotide binding
- NADP binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- cytosol
- integral component of membrane
- organelle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000254090
- Coding exons
- 8
- Length
- 67771
- Individuals with no LoFs
- 125553
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 195
- Defined
- 125748
- p
- 0.000776
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.633 | 319 | 289 | 1.10 | 0.0000141 | 3525 |
| Missense (PolyPhen) | 124 | 124.02 | 0.99981 | 1467 | ||
| Synonymous | 0.727 | 90 | 99.2 | 0.907 | 0.00000472 | 1014 |
| Loss of Function | -0.0623 | 22 | 21.7 | 1.01 | 0.00000111 | 271 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0016 | 0.0016 | notable |
| Latino/Admixed American | 0.0013 | 0.0013 | notable |
| Ashkenazi Jewish | 0.00040 | 0.00040 | rare |
| East Asian | 0.00049 | 0.00044 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00063 | 0.00061 | rare |
| South Asian | 0.0011 | 0.0011 | notable |
| Other | 0.0018 | 0.0018 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: In contrast with other forms of FMO it does not seem to be a drug-metabolizing enzyme.;
Recessive Scores
- pRec
- 0.0903
Intolerance Scores
- LoFtool
- 0.978
- RVIS EVS
- 0.07
- RVIS percentile EVS
- 58.96
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0707
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |