FMO5

Summary

FMO5 (flavin containing dimethylaniline monoxygenase 5, HGNC:3773) is a protein-coding gene on chromosome 1q21.1, encoding Flavin-containing monooxygenase 5 (P49326). Acts as a Baeyer-Villiger monooxygenase on a broad range of substrates.

Metabolic N-oxidation of the diet-derived amino-trimethylamine (TMA) is mediated by flavin-containing monooxygenase and is subject to an inherited FMO3 polymorphism in man resulting in a small subpopulation with reduced TMA N-oxidation capacity resulting in fish odor syndrome Trimethylaminuria. Three forms of the enzyme, FMO1 found in fetal liver, FMO2 found in adult liver, and FMO3 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. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2330 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Disputed, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 13 total — 4 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001461

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3773
Approved symbol	FMO5
Name	flavin containing dimethylaniline monoxygenase 5
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000131781
Ensembl biotype	protein_coding
OMIM	603957
Entrez	2330

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 32 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000254090, ENST00000369272, ENST00000441068, ENST00000478432, ENST00000527849, ENST00000533174, ENST00000533848, ENST00000578284, ENST00000619062, ENST00000865847, ENST00000865848, ENST00000865849, ENST00000865850, ENST00000865851, ENST00000865852, ENST00000865853, ENST00000865854, ENST00000865855, ENST00000865856, ENST00000865857, ENST00000865858, ENST00000865859, ENST00000865860, ENST00000865861, ENST00000865862, ENST00000865863, ENST00000865864, ENST00000865865, ENST00000865866, ENST00000865867, ENST00000865868, ENST00000865869, ENST00000865870, ENST00000942493, ENST00000942494

RefSeq mRNA: 3 — MANE Select: NM_001461 NM_001144829, NM_001144830, NM_001461

CCDS: CCDS44209, CCDS44210, CCDS926

Canonical transcript exons

ENST00000254090 — 9 exons

Exon	Start	End
ENSE00001731647	147186261	147187245
ENSE00002691016	147212393	147212535
ENSE00002696316	147213308	147213470
ENSE00002701412	147215754	147215942
ENSE00002723881	147208852	147209051
ENSE00003729001	147224895	147225066
ENSE00003742312	147190177	147190249
ENSE00003743112	147201152	147201504
ENSE00003846738	147225287	147225339

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 97.66.

FANTOM5 (CAGE): breadth broad, TPM avg 3.3259 / max 356.5242, expressed in 725 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14210	2.3788	363
14213	0.4675	277
14212	0.1896	106
14214	0.1677	71
14211	0.0583	18
14208	0.0339	19
14209	0.0303	11

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	97.66	gold quality
liver	UBERON:0002107	96.34	gold quality
rectum	UBERON:0001052	94.68	gold quality
jejunal mucosa	UBERON:0000399	94.16	gold quality
buccal mucosa cell	CL:0002336	93.06	gold quality
duodenum	UBERON:0002114	92.90	gold quality
body of pancreas	UBERON:0001150	91.64	gold quality
body of stomach	UBERON:0001161	90.95	gold quality
colonic mucosa	UBERON:0000317	90.06	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.86	gold quality
right lung	UBERON:0002167	89.05	gold quality
stomach	UBERON:0000945	88.46	gold quality
ileal mucosa	UBERON:0000331	88.04	gold quality
lower lobe of lung	UBERON:0008949	87.97	gold quality
small intestine Peyer’s patch	UBERON:0003454	87.80	gold quality
monocyte	CL:0000576	87.70	gold quality
gall bladder	UBERON:0002110	87.50	gold quality
small intestine	UBERON:0002108	87.45	gold quality
mononuclear cell	CL:0000842	87.05	gold quality
minor salivary gland	UBERON:0001830	86.55	gold quality
leukocyte	CL:0000738	86.53	gold quality
bronchial epithelial cell	CL:0002328	86.43	gold quality
pancreas	UBERON:0001264	85.66	gold quality
transverse colon	UBERON:0001157	85.55	gold quality
nephron tubule	UBERON:0001231	84.94	gold quality
mucosa of transverse colon	UBERON:0004991	84.43	gold quality
saliva-secreting gland	UBERON:0001044	84.23	gold quality
epithelium of bronchus	UBERON:0002031	83.87	gold quality
secondary oocyte	CL:0000655	83.71	gold quality
colonic epithelium	UBERON:0000397	83.62	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	22.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

87 targeting FMO5, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 4)

• fmo5 displayed a significant, dominant liver-specific mRNA profile. (PMID:16183778)
• absence of the typical characteristic sequence motifs sets human FMO5 apart from all characterized Baeyer-Villiger mono-oxygenases so far. These findings open new perspectives in human oxidative metabolism (PMID:26771671)
• Report relatively stable FMO5 expression throughout development. (PMID:26839369)
• Nabumetone and pentoxifylline, two widely used pharmaceuticals, were thereby demonstrated to be efficiently oxidized in vitro by FMO5 to the corresponding acetate esters with high selectivity. (PMID:28783300)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fmo5	ENSMUSG00000028088
rattus_norvegicus	Fmo5	ENSRNOG00000018076
caenorhabditis_elegans		WBGENE00001476
caenorhabditis_elegans		WBGENE00001478
caenorhabditis_elegans		WBGENE00001480
caenorhabditis_elegans	C01H6.4	WBGENE00007254
caenorhabditis_elegans	C46H11.2	WBGENE00016728

Paralogs (5): FMO3 (ENSG00000007933), FMO1 (ENSG00000010932), FMO4 (ENSG00000076258), FMO2 (ENSG00000094963), FOXRED2 (ENSG00000100350)

Protein

Protein identifiers

Flavin-containing monooxygenase 5 — P49326 (reviewed: P49326)

Alternative names: Baeyer-Villiger monooxygenase 1, Dimethylaniline monooxygenase [N-oxide-forming] 5, Dimethylaniline oxidase 5, NADPH oxidase

All UniProt accessions (4): E9PJF3, E9PP51, E9PQ84, P49326

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a Baeyer-Villiger monooxygenase on a broad range of substrates. Catalyzes the insertion of an oxygen atom into a carbon-carbon bond adjacent to a carbonyl, which converts ketones to esters. Active on diverse carbonyl compounds, whereas soft nucleophiles are mostly non- or poorly reactive. In contrast with other forms of FMO it is non- or poorly active on ‘classical’ substrates such as drugs, pesticides, and dietary components containing soft nucleophilic heteroatoms. Able to oxidize drug molecules bearing a carbonyl group on an aliphatic chain, such as nabumetone and pentoxifylline. Also, in the absence of substrates, shows slow but yet significant NADPH oxidase activity. Acts as a positive modulator of cholesterol biosynthesis as well as glucose homeostasis, promoting metabolic aging via pleiotropic effects.

Subcellular location. Microsome membrane. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in fetal and adult liver.

Similarity. Belongs to the FMO family.

Isoforms (3)

UniProt ID	Names	Canonical?
P49326-1	1	yes
P49326-2	2
P49326-3	3

RefSeq proteins (3): NP_001138301, NP_001138302, NP_001452* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000960	Flavin_mOase	Family
IPR002257	Flavin_mOase_5	Family
IPR020946	Flavin_mOase-like	Family
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR050346	FMO-like	Family

Pfam: PF00743

Enzyme classification (BRENDA):

• EC 1.14.13.8 — flavin-containing monooxygenase (BRENDA: 30 organisms, 458 substrates, 77 inhibitors, 260 Km, 123 kcat entries)

Substrate kinetics (BRENDA)

72 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
METHIMAZOLE	0.007–0.5758	18
TAMOXIFEN	0.0013–0.121	15
INDOLE	0.005–0.9	13
BENZYDAMINE	0.0186–0.0659	11
ETHIONAMIDE	0.104–2.131	10
METHYL P-TOLYL SULFIDE	0.0048–10.2	10
FENTHION	0.145–0.351	9
MERCAPTOIMIDAZOLE	0.018–0.0527	9
NADPH	0.0031–0.132	9
TRIMETHYLAMINE	0.0015–0.58	9
SULINDAC SULFIDE	0.0101–0.0163	8
CHLORPROMAZINE	0.022–0.08	7
IMIPRAMINE	0.0047–0.02	7
L-METHIONINE	2.8–48	6
10-[(N,N-DIMETHYLAMINOOCTYL)-2-(TRIFLUOROMETHYL)	15–38	5

Catalyzed reactions (Rhea), 10 shown:

• NADPH + O2 + H(+) = H2O2 + NADP(+) (RHEA:11260)
• N,N-dimethylaniline + NADPH + O2 + H(+) = N,N-dimethylaniline N-oxide + NADP(+) + H2O (RHEA:24468)
• heptan-2-one + NADPH + O2 + H(+) = pentyl acetate + NADP(+) + H2O (RHEA:54836)
• octan-3-one + NADPH + O2 + H(+) = pentyl propanoate + NADP(+) + H2O (RHEA:54840)
• hexan-3-one + NADPH + O2 + H(+) = ethyl butanoate + NADP(+) + H2O (RHEA:54844)
• hexan-3-one + NADPH + O2 + H(+) = propyl propanoate + NADP(+) + H2O (RHEA:54848)
• heptan-4-one + NADPH + O2 + H(+) = propyl butanoate + NADP(+) + H2O (RHEA:54852)
• octan-3-one + NADPH + O2 + H(+) = ethyl hexanoate + NADP(+) + H2O (RHEA:54856)
• (2E)-geranial + NADPH + O2 + H(+) = (1E)-2,6-dimethylhepta-1,5-dien-1-yl formate + NADP(+) + H2O (RHEA:54860)
• sulcatone + NADPH + O2 + H(+) = 4-methylpent-3-en-1-yl acetate + NADP(+) + H2O (RHEA:54864)

UniProt features (22 total): modified residue 7, binding site 5, splice variant 4, sequence variant 3, chain 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49326-F1	95.03	0.92

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 10–14; 33; 41–42; 62–63; 196–199

Post-translational modifications (7): 58, 280, 284, 401, 5, 54, 56

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 220 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GSE45365_NK_CELL_VS_CD8A_DC_UP, MODULE_93, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, AP4_Q6, DARWICHE_PAPILLOMA_PROGRESSION_RISK, CAGCTG_AP4_Q5, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS, FONTAINE_PAPILLARY_THYROID_CARCINOMA_UP, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A4, HSIAO_LIVER_SPECIFIC_GENES, GOBP_LIPID_METABOLIC_PROCESS, MODULE_88

GO Biological Process (3): lipid metabolic process (GO:0006629), xenobiotic metabolic process (GO:0006805), regulation of cholesterol metabolic process (GO:0090181)

GO Molecular Function (8): monooxygenase activity (GO:0004497), N,N-dimethylaniline monooxygenase activity (GO:0004499), NAD(P)H oxidase H2O2-forming activity (GO:0016174), flavin adenine dinucleotide binding (GO:0050660), NADP binding (GO:0050661), oxidoreductase activity (GO:0016491), trimethylamine monooxygenase activity (GO:0034899), hypotaurine monooxygenase activity (GO:0047822)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen	3
cytoplasm	2
cellular anatomical structure	2
primary metabolic process	1
metabolic process	1
cellular response to xenobiotic stimulus	1
cholesterol metabolic process	1
regulation of steroid metabolic process	1
regulation of small molecule metabolic process	1
oxidoreductase activity	1
oxidoreductase activity, acting on NAD(P)H, oxygen as acceptor	1
nucleotide binding	1
anion binding	1
adenyl nucleotide binding	1
catalytic activity	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1

Protein interactions and networks

STRING

1754 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FMO5	GJA5	P36382	724
FMO5	ACP6	Q9NPH0	697
FMO5	RB1	P06400	688
FMO5	CHD1L	Q86WJ1	658
FMO5	NBPF11	Q86T75	654
FMO5	NPR1	P16066	653
FMO5	PRKAB2	O43741	593
FMO5	GPHRA	B7ZAQ6	576
FMO5	PGR	P06401	551
FMO5	GJA8	P48165	549
FMO5	BCL9	O00512	507
FMO5	DHRS11	Q6UWP2	462
FMO5	HDC	P19113	453
FMO5	WNT4	P56705	439
FMO5	GSC	P56915	437

IntAct

3 interactions, top by confidence:

A	B	Type	Score
FMO5	OGA	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): SRC (Affinity Capture-MS), ERICH5 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), MGEA5 (Affinity Capture-MS), HERC1 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), HERC1 (Affinity Capture-MS), SRC (Affinity Capture-MS), MGEA5 (Affinity Capture-MS), GAPDH (Cross-Linking-MS (XL-MS)), FMO5 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0M4FCN7, B4G0F3, B8BKI7, C6JS30, E0CTF3, F4JJJ3, K7PEY4, M1BYJ7, O23617, O23732, O48538, O80765, O81210, P28492, P49109, P49326, P49328, Q10D00, Q1JPL4, Q2HXK9, Q2HXL0, Q2R483, Q3TMV7, Q5REJ2, Q5ZAJ0, Q68FS6, Q6DIZ8, Q6J2K5, Q6PH52, Q8L7M0, Q8VZ59, Q8WU10, Q93Z70, Q948T9, Q948U0, Q94A08, Q94BV7, Q9FIJ0, Q9FN41, Q9LFM5

Diamond homologs: A0A0B5RNJ4, A3SLM3, A3VVZ4, B6BQB2, B8EIZ7, P16549, P49109, P49326, Q01740, Q04799, Q1V023, Q5LT63, Q8MP06, O23024, O60774, P17635, P31512, P36365, P36366, P36367, P50285, P97872, Q28505, Q5REK0, Q6IRI9, Q8HZ69, Q8HZ70, Q8K2I3, Q8K4C0, Q93Y23, Q99518, Q9C8U0, Q9FWW6, Q9SH25, Q9SS04, Q9SXD5, A0A0C2WKN2, F2K079, P97501, Q8HYJ9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

13 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	4
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1711249	GRCh37/hg19 1q21.1-21.2(chr1:146626685-147597284)x1	Pathogenic
1808730	GRCh37/hg19 1q21.1-21.2(chr1:145768023-147929323)x1	Pathogenic
565167	GRCh37/hg19 1q21.1-21.2(chr1:145792037-147929323)x1	Pathogenic
625537	GRCh37/hg19 1q21.1-21.2(chr1:145103956-147220326)	Pathogenic

SpliceAI

1646 predictions. Top by Δscore:

Variant	Effect	Δscore
1:147187241:CATAC:C	acceptor_gain	1.0000
1:147190172:CTTA:C	donor_loss	1.0000
1:147190174:TACC:T	donor_loss	1.0000
1:147190175:A:C	donor_loss	1.0000
1:147201525:CAAG:C	acceptor_gain	1.0000
1:147201526:A:T	acceptor_gain	1.0000
1:147212535:CCTGC:C	acceptor_loss	1.0000
1:147212536:CTGC:C	acceptor_loss	1.0000
1:147212537:T:G	acceptor_loss	1.0000
1:147213204:A:AC	donor_gain	1.0000
1:147213205:C:CC	donor_gain	1.0000
1:147213205:CTT:C	donor_gain	1.0000
1:147213290:T:TA	donor_gain	1.0000
1:147215768:A:AC	donor_gain	1.0000
1:147215769:C:CC	donor_gain	1.0000
1:147215795:ACAT:A	donor_gain	1.0000
1:147215796:CATC:C	donor_gain	1.0000
1:147215798:T:TA	donor_gain	1.0000
1:147215938:TTTTC:T	acceptor_gain	1.0000
1:147224892:TACCT:T	donor_loss	1.0000
1:147224894:C:CA	donor_loss	1.0000
1:147187243:TAC:T	acceptor_gain	0.9900
1:147187246:CTA:C	acceptor_loss	0.9900
1:147187247:T:A	acceptor_loss	0.9900
1:147187641:T:TA	donor_gain	0.9900
1:147190175:A:AC	donor_gain	0.9900
1:147190176:C:CC	donor_gain	0.9900
1:147190176:CCT:C	donor_gain	0.9900
1:147190176:CCTT:C	donor_gain	0.9900
1:147190247:GACC:G	acceptor_loss	0.9900

AlphaMissense

3541 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:147224906:A:G	W42R	0.998
1:147224906:A:T	W42R	0.998
1:147213354:G:C	C147W	0.996
1:147215883:T:A	K65N	0.996
1:147215883:T:G	K65N	0.996
1:147224904:C:A	W42C	0.996
1:147224904:C:G	W42C	0.996
1:147209040:G:C	S214R	0.995
1:147209040:G:T	S214R	0.995
1:147209042:T:G	S214R	0.995
1:147213419:A:G	W126R	0.995
1:147213419:A:T	W126R	0.995
1:147215884:T:A	K65I	0.995
1:147201469:A:G	L289P	0.994
1:147209024:A:G	W220R	0.994
1:147209024:A:T	W220R	0.994
1:147212501:A:C	S174R	0.994
1:147212501:A:T	S174R	0.994
1:147212503:T:G	S174R	0.994
1:147213349:C:T	G149D	0.994
1:147225001:C:T	G10E	0.994
1:147201358:A:T	V326D	0.993
1:147215865:A:C	S71R	0.993
1:147215865:A:T	S71R	0.993
1:147215867:T:G	S71R	0.993
1:147224914:C:T	G39E	0.993
1:147224988:G:C	S14R	0.993
1:147224988:G:T	S14R	0.993
1:147224990:T:G	S14R	0.993
1:147225010:G:T	A7D	0.993

dbSNP variants (sampled 300 via entrez): RS1000027603 (1:147195799 C>G), RS1000030214 (1:147228134 T>C), RS1000169204 (1:147200794 A>G), RS1000336950 (1:147214706 C>T), RS1000389533 (1:147214387 G>T), RS1000489353 (1:147227919 C>A), RS1000683397 (1:147207956 A>C), RS1000881698 (1:147219635 C>A,T), RS1000981685 (1:147226908 C>T), RS1001033896 (1:147226589 A>G), RS1001084463 (1:147226195 G>A), RS1001084897 (1:147190403 C>A,T), RS1001333681 (1:147219247 T>C), RS1001503333 (1:147207163 A>G), RS1001607631 (1:147214117 T>A)

Disease associations

OMIM: gene MIM:603957 | disease phenotypes: MIM:612475

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
congenital heart disease	Disputed	AD

Mondo (2): chromosome 1q21.1 duplication syndrome (MONDO:0012915), congenital heart disease (MONDO:0005453)

Orphanet (1): 1q21.1 microduplication syndrome (Orphanet:250994)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002616_11	Mitochondrial DNA levels	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006312	mitochondrial DNA measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
C567290	Chromosome 1q21.1 Duplication Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3430871 (SINGLE PROTEIN), CHEMBL3542432 (PROTEIN FAMILY)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7541245	Efficacy	3	metformin	Diabetes Mellitus

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7541245	CHD1L, FMO5	3	2.75	1	metformin

CTD chemical–gene interactions

74 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects cotreatment, affects expression, decreases expression, decreases methylation	7
Tetrachlorodibenzodioxin	affects expression, decreases expression	4
Cyclosporine	decreases expression	4
perfluorooctane sulfonic acid	decreases expression, increases expression	3
perfluorooctanoic acid	decreases expression, increases expression	2
Troglitazone	decreases expression	2
Nickel	decreases expression	2
Quercetin	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression	2
Aflatoxin B1	decreases expression, affects expression	2
beta-Naphthoflavone	decreases expression	2
perfluorodecanesulfonic acid	increases expression	1
dicrotophos	decreases expression	1
lasiocarpine	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
benzo(b)fluoranthene	affects cotreatment, affects expression	1
bisphenol A	affects expression	1
chlortoluron	decreases expression	1
senecionine	decreases expression	1
senkirkine	decreases expression	1
VX-agent	decreases expression	1
pyrithione zinc	decreases expression, increases expression	1
cinnamaldehyde	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
1,2,5,6-dibenzanthracene	affects cotreatment, affects expression	1

ChEMBL screening assays

14 unique, capped per target: 14 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3531399	ADMET	Drug level assessed as human recombinant FMO5-mediated compound formation from 10 uM ER-879819 in presence NADPH after 60 mins by LC-MS/MS method	A Baeyer-Villiger oxidation specifically catalyzed by human flavin-containing monooxygenase 5. — Drug Metab Dispos

Clinical trials (associated diseases)

301 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE