FMO3

flavin containing dimethylaniline monoxygenase 3, the group of Flavin containing monooxygenases|MicroRNA protein coding host genes

Basic information

Region (hg38): 1:171090901-171117819

Links

ENSG00000007933 ∙ NCBI:2328 ∙ OMIM:136132 ∙ HGNC:3771 ∙ Uniprot:P31513 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• severe primary trimethylaminuria (Strong), mode of inheritance: AR
• severe primary trimethylaminuria (Supportive), mode of inheritance: AR
• trimethylaminuria (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Trimethylaminuria	AR	Biochemical	Treatment may involve dietary modification (eg, to restrict trimethylamine precursors), and medical/dietary treatment (eg, with agents such as metronidazole, neomycin, lactulose, copper chlorphyllin, or activated charcoal) as well as riboflavin supplementation (the use of specific pH soaps may be beneficial as well)	Biochemical	7474897; 9398858; 9846928; 10646019; 10485731; 12653714; 12893987; 12938085; 15565078; 16601883; 22126753

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FMO3 gene.

• not_provided (167 variants)
• Trimethylaminuria (99 variants)
• Inborn_genetic_diseases (43 variants)
• not_specified (20 variants)
• FMO3-related_disorder (9 variants)
• See_cases (2 variants)
• FMO3_activity,_decreased (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FMO3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001002294.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	48	4	53
missense	3	29	60	13	2	107
nonsense	20	10				30
start loss	1	1				2
frameshift	16	13				29
splice donor/acceptor (+/-2bp)	1	12	1			14
Total	41	65	62	61	6

Highest pathogenic variant AF is 0.00236895

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FMO3	protein_coding	protein_coding	ENST00000367755	8	26942

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.51e-16	0.00408	125507	0	236	125743	0.000939

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.163	300	292	1.03	0.0000147	3545
Missense in Polyphen		110	97.601	1.127		1284
Synonymous	1.08	92	106	0.867	0.00000562	991
Loss of Function	-0.464	22	19.8	1.11	9.08e-7	248

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000855	0.000855
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00294	0.00294
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000904	0.000897
Middle Eastern	0.00294	0.00294
South Asian	0.00144	0.00144
Other	0.00131	0.00130

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an important role in the metabolism of trimethylamine (TMA), via the production of TMA N-oxide (TMAO). Is also able to perform S-oxidation when acting on sulfide compounds (PubMed:9224773). {ECO:0000250|UniProtKB:P97501, ECO:0000269|PubMed:9224773}.
• Pathway: Drug metabolism - cytochrome P450 - Homo sapiens (human);Busulfan Pathway, Pharmacodynamics;Tamoxifen Pathway, Pharmacokinetics;Nicotine Pathway, Pharmacokinetics;Nicotine Metabolism Pathway;Nicotine Action Pathway;Tamoxifen Action Pathway;Tamoxifen Metabolism Pathway;Nicotine Metabolism;Catalytic cycle of mammalian Flavin-containing MonoOxygenases (FMOs);Tamoxifen metabolism;Metapathway biotransformation Phase I and II;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Phase I - Functionalization of compounds;FMO oxidises nucleophiles;Biological oxidations;Metabolism;Selenoamino acid metabolism;nicotine degradation IV (Consensus)

Recessive Scores

• pRec: 0.118

Intolerance Scores

• loftool: 0.997
• rvis_EVS: 1.04
• rvis_percentile_EVS: 91.31

Haploinsufficiency Scores

• pHI: 0.0817
• hipred: N
• hipred_score: 0.170
• ghis: 0.408

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.178

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fmo3

Gene ontology

• Biological process: xenobiotic metabolic process;oxidation-reduction process
• Cellular component: endoplasmic reticulum membrane;integral component of membrane;organelle membrane;intracellular membrane-bounded organelle
• Molecular function: monooxygenase activity;N,N-dimethylaniline monooxygenase activity;protein binding;trimethylamine monooxygenase activity;flavin adenine dinucleotide binding;NADP binding