FMO4

protein-coding

flavin containing dimethylaniline monoxygenase 4, the group of Flavin containing monooxygenases

Gene summary

Metabolic N-oxidation of diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in man. This results in a small subpopulation with reduced TMA N-oxidation capacity and causes fish odor syndrome (Trimethylaminuria). Three forms of the enzyme 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. [provided by RefSeq, Jan 2015]

Previous symbols:

FMO2

MANE transcript

NM_002022.3

Inheritance

—

ClinVar variants

U:82B:7

Top phenotype

Trimethylaminuria

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr1:171,314,183-171,342,084

External References & Databases

Ensembl (ENSG00000076258)

Transcript & Mutation Effects

hg38 • Region Span ~27.9 kb

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GenCC 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 FMO4 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 72

not providedTotal: 7

TrimethylaminuriaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002022.3. 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 clinvar		2 clinvar	3
missense			77 clinvar	4 clinvar	1 clinvar	82
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	82	4	3	89

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002022.3	RefSeq	NP_002013.1	8	MANE Select
ENST00000367749.4	Ensembl	ENSP00000356723.3	8	MANE Select
ENST00000853709.1	Ensembl	ENSP00000523768.1	5	Standard
ENST00000853709.2	Ensembl	ENSP00000523768.1	5	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

drug catabolic process
oxidation-reduction process

Molecular Function

monooxygenase activity
N,N-dimethylaniline monooxygenase activity
flavin adenine dinucleotide binding
NADP binding

Cellular Component

endoplasmic reticulum membrane
integral component of membrane
organelle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367749
Coding exons: 8
Length: 27877
Individuals with no LoFs: 125643
Homozygous LoFs: 1
Heterozygous LoFs: 95
Defined: 125739
p: 0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.437	276	297	0.929	0.0000146	3670
Missense (PolyPhen)		104	109.64	0.94858		1391
Synonymous	0.168	105	107	0.979	0.00000540	1057
Loss of Function	0.916	18	22.7	0.793	0.00000112	290

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00018	0.00018	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.0020	0.0020	notable
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00029	0.00027	rare
South Asian	0.00036	0.00036	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides.;

Recessive Scores

pRec: 0.112

Intolerance Scores

RVIS EVS: 0.55
RVIS percentile EVS: 81.6

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.146

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium