FMO3

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

Basic information

Region (hg38): 1:171090900-171117819

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 (79 variants)
• Trimethylaminuria (68 variants)
• not specified (21 variants)
• Inborn genetic diseases (12 variants)
• See cases (3 variants)
• FMO3 activity, decreased (1 variants)
• FMO3-related condition (1 variants)
• - (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	14	5	24
missense	2	12	27	8	4	53
nonsense	15	1				16
start loss						0
frameshift	9		1			10
inframe indel						0
splice donor/acceptor (+/-2bp)	1	2	1			4
splice region				3		3
non coding			9	8	4	21
Total	27	15	43	30	13

Highest pathogenic variant AF is 0.000355

Variants in FMO3

This is a list of pathogenic ClinVar variants found in the FMO3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-171090963-G-A		Trimethylaminuria	Uncertain significance (Jan 13, 2018)
1-171092652-G-C		not specified	Uncertain significance (May 09, 2023)
1-171092659-A-G			Pathogenic (Jan 20, 2024)
1-171092668-A-T			Pathogenic (Jun 11, 2023)
1-171092672-TG-T			Pathogenic (Nov 17, 2023)
1-171092678-TCATTGGAG-T			Pathogenic (Oct 08, 2023)
1-171092679-C-T			Likely benign (Jan 11, 2024)
1-171092687-C-T		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)
1-171092700-C-T			Likely benign (Dec 28, 2023)
1-171092708-C-T		FMO3-related disorder	Uncertain significance (Dec 04, 2023)
1-171092739-G-A			Likely benign (Jan 05, 2024)
1-171092752-G-A		Trimethylaminuria	Pathogenic (Aug 01, 2003)
1-171092756-A-G		Inborn genetic diseases	Likely benign (Oct 02, 2023)
1-171092759-G-GC			Pathogenic (Apr 17, 2023)
1-171092791-G-T			Likely pathogenic (Jul 10, 2017)
1-171092799-C-G			Likely benign (Dec 29, 2023)
1-171092801-T-C			Likely benign (Dec 14, 2023)
1-171092802-G-A			Likely benign (Jan 25, 2024)
1-171092803-T-C		Trimethylaminuria	Uncertain significance (Jan 12, 2018)
1-171092805-G-C			Likely benign (Jan 29, 2024)
1-171101127-A-T		FMO3-related disorder	Likely benign (Jul 07, 2020)
1-171103783-A-G			Likely pathogenic (Oct 04, 2023)
1-171103803-A-G			Likely pathogenic (Apr 14, 2023)
1-171103806-G-A		Trimethylaminuria	Pathogenic (Sep 01, 1999)
1-171103822-C-G			Pathogenic (Jul 17, 2023)

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