FMO1
protein-codingflavin containing dimethylaniline monoxygenase 1, 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. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~37.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to FMO1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001282693.2. 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 | 1 | 1 | ||||
| missense | 66 | 5 | 2 | 73 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 67 | 6 | 2 | 75 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001269622.1 | 8 | MANE Select | |
| Ensembl | ENSP00000481732.1 | 8 | MANE Select | |
| RefSeq | NP_001269621.1 | 8 | Standard | |
| RefSeq | NP_001269623.1 | 7 | 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
- Tamoxifen Pathway, Pharmacokinetics
- Tamoxifen Action Pathway
- Tamoxifen Metabolism Pathway
Biological Process
- organic acid metabolic process
- xenobiotic metabolic process
- response to osmotic stress
- toxin metabolic process
- drug metabolic process
Molecular Function
- monooxygenase activity
- N,N-dimethylaniline monooxygenase activity
- protein binding
- flavin adenine dinucleotide binding
- NADP binding
Cellular Component
- endoplasmic reticulum lumen
- endoplasmic reticulum membrane
- integral component of membrane
- organelle membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000354841
- Coding exons
- 8
- Length
- 37480
- Individuals with no LoFs
- 125689
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 59
- Defined
- 125748
- p
- 0.000235
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.05 | 235 | 285 | 0.825 | 0.0000139 | 3500 |
| Missense (PolyPhen) | 78 | 104.59 | 0.74575 | 1271 | ||
| Synonymous | -0.748 | 113 | 103 | 1.09 | 0.00000515 | 1025 |
| Loss of Function | 1.20 | 19 | 25.5 | 0.745 | 0.00000158 | 276 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00025 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00082 | 0.00082 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00027 | 0.00027 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. Form I catalyzes the N-oxygenation of secondary and tertiary amines.;
Recessive Scores
- pRec
- 0.155
Intolerance Scores
- LoFtool
- 0.688
- RVIS EVS
- 1.09
- RVIS percentile EVS
- 91.85
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.114
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |