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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FMO4
flavin containing dimethylaniline monoxygenase 4
Chromosome 1 · 1q24.3
NCBI Gene: 2329Ensembl: ENSG00000076258.11HGNC: HGNC:3772UniProt: P31512
17PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingxenobiotic metabolic processN,N-dimethylaniline monooxygenase activityendoplasmic reticulum membraneneurodegenerative diseasealcohol drinkingbrain aneurysmAbnormal nasolacrimal system morphology
✦AI Summary

FMO4 (flavin containing dimethylaniline monoxygenase 4) is a member of the flavin-containing monooxygenase family involved in xenobiotic metabolism and cellular protection mechanisms. The protein exhibits N,N-dimethylaniline monooxygenase activity and participates in the oxidative metabolism of various xenobiotics including drugs and pesticides 1. FMO4 demonstrates distinct tissue-specific localization patterns, with immunoreactivity detected in liver periportal regions (opposite to FMO1/FMO3 distribution) and kidney distal tubules, proximal tubules, collecting tubules, and glomerulus 2. Unlike some FMO family members, FMO4 protein expression has been confirmed in mouse, rat, and human liver and kidney microsomes 2. Related FMO family members exhibit additional protective functions beyond xenobiotic metabolism, including roles in lipid metabolism regulation (FMO2), cardioprotection through disulfide bond catalysis (FMO2), and angiogenesis promotion (FMO2) 345. The FMO family also contributes to TMAO synthesis, which has implications for metabolic dysfunction and reproductive health 67. While FMO4's specific physiological roles require further investigation, its unique tissue distribution and confirmed expression across species suggest important metabolic functions in detoxification and cellular homeostasis.

Sources cited
1
FMO family members function in pesticide metabolism as substrates, inhibitors and inducers of drug-metabolizing enzymes
PMID: 8597134
2
FMO4 shows distinct tissue localization in liver periportal regions and various kidney regions, with confirmed protein expression in mouse, rat, and human tissues
PMID: 19307449
3
FMO2 protects against fatty liver disease by suppressing SREBP1 transport and lipogenesis
PMID: 37874228
4
FMO2 provides cardioprotection through disulfide bond catalytic activity and ER stress inhibition
PMID: 39480513
5
FMO2 promotes angiogenesis via regulation of N-acetylornithine
PMID: 41053533
6
FMO3 synthesizes TMAO which binds PERK and promotes metabolic dysfunction
PMID: 31543404
7
FMO3-derived TMAO supports decidualization and prevents recurrent spontaneous abortion
PMID: 41512878
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.39Weak
alcohol drinkingOpen Targets
0.33Weak
brain aneurysmOpen Targets
0.32Weak
Abnormal nasolacrimal system morphologyOpen Targets
0.23Weak
trimethylaminuriaOpen Targets
0.12Weak
sinoatrial node disorderOpen Targets
0.08Suggestive
glaucomaOpen Targets
0.02Suggestive
clear cell renal carcinomaOpen Targets
0.02Suggestive
thrombophiliaOpen Targets
0.02Suggestive
Abnormality of refractionOpen Targets
0.02Suggestive
auditory system diseaseOpen Targets
0.02Suggestive
SepsisOpen Targets
0.02Suggestive
colorectal carcinomaOpen Targets
0.01Suggestive
ulcerative colitisOpen Targets
0.01Suggestive
osteoporosisOpen Targets
0.01Suggestive
kidney oncocytomaOpen Targets
0.01Suggestive
transitional cell carcinoma of kidneyOpen Targets
0.01Suggestive
asthmaOpen Targets
0.01Suggestive
IGA glomerulonephritisOpen Targets
0.01Suggestive
juvenile dermatomyositisOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NAT1Shared pathway100%NAT2Shared pathway100%AOX1Shared pathway100%CMBLShared pathway100%RBBP9Shared pathway100%CYP3A4Protein interaction98%
Tissue Expression6 tissues
Liver
100%
Heart
32%
Ovary
16%
Lung
9%
Bone Marrow
7%
Brain
2%
Gene Interaction Network
Click a node to explore
FMO4NAT1NAT2AOX1CMBLRBBP9CYP3A4
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P31512
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.33LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.98 [0.73–1.33]
RankingsWhere FMO4 stands among ~20K protein-coding genes
  • #15,002of 20,598
    Most Researched17
  • #13,949of 17,882
    Most Constrained (LOEUF)1.33
Genes detectedFMO4
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
FMO2 ameliorates nonalcoholic fatty liver disease by suppressing ER-to-Golgi transport of SREBP1.
PMID: 37874228
Hepatology · 2025
1.00
2
SFRP2/DPP4 and FMO1/LSP1 Define Major Fibroblast Populations in Human Skin.
PMID: 29080679
J Invest Dermatol · 2018
0.90
3
Trimethylamine N-Oxide Binds and Activates PERK to Promote Metabolic Dysfunction.
PMID: 31543404
Cell Metab · 2019
0.80
4
Flavin-containing monooxygenase 2 confers cardioprotection in ischemia models through its disulfide bond catalytic activity.
PMID: 39480513
J Clin Invest · 2024
0.70
5
Endometrial stromal cell-derived TMAO sustains decidualization to prevent recurrent spontaneous abortion.
PMID: 41512878
Cell Metab · 2026
0.60