FMO2

protein-coding

flavin containing dimethylaniline monoxygenase 2, the group of Flavin containing monooxygenases

Gene summary

This gene encodes a flavin-containing monooxygenase family member. It is an NADPH-dependent enzyme that catalyzes the N-oxidation of some primary alkylamines through an N-hydroxylamine intermediate. However, some human populations contain an allele (FMO2*2A) with a premature stop codon, resulting in a protein that is C-terminally-truncated, has no catalytic activity, and is likely degraded rapidly. This gene is found in a cluster with other related family members on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

MANE transcript

NM_001460.5

Inheritance

—

ClinVar variants

U:71B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.67

Max pathogenic AF

—

Genomic locus

chr1:171,185,249-171,212,686

External References & Databases

Ensembl (ENSG00000094963)

Transcript & Mutation Effects

hg38 • Region Span ~27.4 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 FMO2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 69

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001460.5. 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 clinvar		2
missense			69 clinvar	5 clinvar		74
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	71	7	0	78

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001460.5	RefSeq	NP_001451.2	8	MANE Select
ENST00000209929.10	Ensembl	ENSP00000209929.8	8	MANE Select
NM_001301347.2	RefSeq	NP_001288276.1	4	Standard
NM_001365900.2	RefSeq	NP_001352829.1	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
Catalytic cycle of mammalian Flavin-containing MonoOxygenases (FMOs)
Metapathway biotransformation Phase I and II
Phase I - Functionalization of compounds

Biological Process

organic acid metabolic process
NADP metabolic process
xenobiotic metabolic process
toxin metabolic process
drug metabolic process

Molecular Function

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

Cellular Component

endoplasmic reticulum membrane
membrane
organelle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000441535
Coding exons: 8
Length: 27476
Individuals with no LoFs: 111898
Homozygous LoFs: 842
Heterozygous LoFs: 13007
Defined: 125747
p: 0.0567

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.0993	256	261	0.983	0.0000136	3111
Missense (PolyPhen)		86	98.658	0.8717		1233
Synonymous	0.567	85	91.9	0.925	0.00000486	876
Loss of Function	1.36	13	19.5	0.667	9.05e-7	260

Population LoF Frequency

Population	CAF	p-value	Status
African	0.29	0.29	notable
Latino/Admixed American	0.038	0.038	notable
Ashkenazi Jewish	0.090	0.090	notable
East Asian	0.00087	0.00087	rare
Finnish	0.024	0.024	notable
European (Non-Finnish)	0.048	0.048	notable
South Asian	0.053	0.053	notable
Other	0.053	0.053	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the N-oxidation of certain primary alkylamines to their oximes via an N-hydroxylamine intermediate. Inactive toward certain tertiary amines, such as imipramine or chloropromazine. Can catalyze the S-oxidation of methimazole. The truncated form is catalytically inactive. {ECO:0000269|PubMed:9804831}.;

Intolerance Scores

LoFtool: 0.941
RVIS EVS: 2.47
RVIS percentile EVS: 98.61

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.229

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High