FADS1

Summary

FADS1 (fatty acid desaturase 1, HGNC:3574) is a protein-coding gene on chromosome 11q12.2, encoding Acyl-CoA (8-3)-desaturase (O60427). Acts as a front-end fatty acyl-coenzyme A (CoA) desaturase that introduces a cis double bond at carbon 5 located between a preexisting double bond and the carboxyl end of the fatty acyl chain.

The protein encoded by this gene is a member of the fatty acid desaturase (FADS) gene family. Desaturase enzymes regulate unsaturation of fatty acids through the introduction of double bonds between defined carbons of the fatty acyl chain. FADS family members are considered fusion products composed of an N-terminal cytochrome b5-like domain and a C-terminal multiple membrane-spanning desaturase portion, both of which are characterized by conserved histidine motifs. This gene is clustered with family members FADS1 and FADS2 at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization.

Source: NCBI Gene 3992 — RefSeq curated summary.

At a glance

• GWAS associations: 310
• Clinical variants (ClinVar): 28 total
• Druggable target: yes
• MANE Select transcript: NM_013402

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3574
Approved symbol	FADS1
Name	fatty acid desaturase 1
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	D5D, FADSD5, TU12, FADS6
Ensembl gene	ENSG00000149485
Ensembl biotype	protein_coding
OMIM	606148
Entrez	3992

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000350997, ENST00000421879, ENST00000424501, ENST00000433932, ENST00000448607, ENST00000460649, ENST00000466716, ENST00000473263, ENST00000491310, ENST00000496123, ENST00000536991, ENST00000539419, ENST00000539999, ENST00000540767, ENST00000541683, ENST00000542506, ENST00000544309, ENST00000544696, ENST00000545245, ENST00000545405, ENST00000545986, ENST00000935426, ENST00000935427

RefSeq mRNA: 1 — MANE Select: NM_013402 NM_013402

CCDS: CCDS8011

Canonical transcript exons

ENST00000350997 — 12 exons

Exon	Start	End
ENSE00000916427	61812471	61812668
ENSE00001298098	61799627	61802462
ENSE00001302676	61802801	61802926
ENSE00001357242	61804685	61804761
ENSE00001357251	61806664	61806724
ENSE00001802889	61816555	61817003
ENSE00003486369	61803032	61803111
ENSE00003500900	61813243	61813353
ENSE00003589054	61803670	61803767
ENSE00003665185	61810974	61811075
ENSE00003680502	61803363	61803459
ENSE00003788976	61810751	61810879

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 97.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 75.9859 / max 2121.7116, expressed in 1794 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
120036	60.2582	1768
120035	6.7638	1576
120040	3.2333	1270
120034	2.4064	1071
120032	1.4986	928
120033	1.1178	630
206301	0.4109	191
120031	0.2087	91
120041	0.0881	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	97.97	gold quality
ventral tegmental area	UBERON:0002691	97.86	gold quality
superior vestibular nucleus	UBERON:0007227	97.83	gold quality
ventricular zone	UBERON:0003053	97.27	gold quality
dorsal root ganglion	UBERON:0000044	97.26	gold quality
medial globus pallidus	UBERON:0002477	97.20	gold quality
ganglionic eminence	UBERON:0004023	97.13	gold quality
trigeminal ganglion	UBERON:0001675	97.12	gold quality
endometrium epithelium	UBERON:0004811	96.99	gold quality
medulla oblongata	UBERON:0001896	96.98	gold quality
embryo	UBERON:0000922	96.92	gold quality
globus pallidus	UBERON:0001875	96.84	gold quality
inferior vagus X ganglion	UBERON:0005363	96.37	gold quality
subthalamic nucleus	UBERON:0001906	95.93	gold quality
cranial nerve II	UBERON:0000941	95.86	gold quality
right adrenal gland	UBERON:0001233	95.66	gold quality
dorsal plus ventral thalamus	UBERON:0001897	95.61	gold quality
right adrenal gland cortex	UBERON:0035827	95.47	gold quality
mammalian vulva	UBERON:0000997	95.44	gold quality
nipple	UBERON:0002030	95.26	gold quality
adrenal gland	UBERON:0002369	95.21	gold quality
adrenal cortex	UBERON:0001235	95.13	gold quality
corpus callosum	UBERON:0002336	95.13	gold quality
left adrenal gland	UBERON:0001234	94.88	gold quality
choroid plexus epithelium	UBERON:0003911	94.85	gold quality
parietal lobe	UBERON:0001872	94.79	gold quality
pericardium	UBERON:0002407	94.73	gold quality
left adrenal gland cortex	UBERON:0035825	94.69	gold quality
pigmented layer of retina	UBERON:0001782	94.68	gold quality
lateral globus pallidus	UBERON:0002476	94.63	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	196.49
E-CURD-112	yes	32.94
E-MTAB-6678	yes	10.11
E-MTAB-6911	no	604.69
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA, SREBF1

miRNA regulators (miRDB)

162 targeting FADS1, 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-5193	100.00	67.26	1744
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349

Literature-anchored findings (GeneRIF, showing 40)

• This is the first report on characterization of human FADS, and the first cloning and over-expression of FADS from an organism higher than yeast. (PMID:16643857)
• FADS1 FADS2 genetic varients and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids (PMID:16670158)
• support a significant role for reverse Delta5-desaturase as a natural antisense regulator of Delta5-desaturase (PMID:16846730)
• SREBP-1 is involved in the early regulation of delta5 desaturase gene by simvastatin, in THP-1 cells. (PMID:17655842)
• The results indicate that when the supply of FA to HL60 cells is limited, the intracellular content of n-3 and n-6 FA decreases and this leads to upregulation of the desaturases, particularly D5D and D6D. (PMID:17852835)
• strong association of FADS1 gene polymorphisms with the levels of arachidonic acid, which is a precursor of molecules involved in inflammation and immunity processes, cardiovascular disease. (PMID:18320251)
• In populations following a Western diet, subjects carrying FADS haplotypes that are associated with higher desaturase activity may be prone to a proinflammatory response favoring atherosclerotic vascular damage. (PMID:18842780)
• This study showed that genetic variants of FADS1 and FADS2 influence blood lipid and breast milk essential fatty acids in pregnancy and lactation. (PMID:18936223)
• Single nucleotide polymorphisms (SNPs) in the 2 desaturase encoding gene FADS1 is highly associated with the concentration of omega-6 and omega-3 fatty acids. (PMID:19776639)
• Liver Delta-6D and Delta-5D activities in obese patients were 87% and 66% lower than controls (P < 0.001) (PMID:19875987)
• impact of FADS1 genotype on LC-PUFA/lipid metabolism and influence on intellectual development in infants and chronic metabolic diseases [REVIEW] (PMID:19948371)
• Strong associations between variants in the human genes FADS1, and blood levels of polyunsaturated fatty acids have been reported–REVIEW (PMID:20045144)
• Immunofluorescence confocal microscopy performed on BHK-21 and Caco-2 cell lines transiently expressing the two human isoforms, definitively confirmed that hFADS1, but not hFADS2, localizes in mitochondria. (PMID:20060505)
• Lower proportions of docosahexenoic acid in milk from women homozygous for a minor allele in t4his gene could not be compensated for by increasing fish and fish-oil intake. (PMID:20335541)
• A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in life style. (PMID:20364269)
• association between genetic variability in the FADS gene cluster and delt-5 and delta-6 desaturase activities (PMID:20427696)
• Genetic variation in the FADS1 gene potentially interacts with dietary polyunsaurated faatty acid intakes which in turn affects plasma cholesterol concentrations. (PMID:20484448)
• potential role in disease onset and development (Review) (PMID:20565855)
• Genetic variation in the FADS1 FADS2 gene cluster affects n-6 polyunsaturated fatty acid profiles in erythrocytes reflecting altered delta-5-desaturase activity. (PMID:20691134)
• PUFA-composition in young children’s blood is under strong control of the FADS-gene-cluster (PMID:20948998)
• stearoyl coenzyme A desaturase (SCD) and D6D activity, were directly related to diabetes risk in multivariable-adjusted models. (PMID:20980488)
• The rs174537T polymorphism of FADS1 is associated with a lower proportion of arachidonic acid in serum phospholipids and reduced coronary artery disease risk, in association with reduced total- and LDL-cholesterol and lipid peroxides in Koreans (PMID:21040914)
• Genetic variants of the fatty acid desaturase gene cluster predict amounts of red blood cell docosahexaenoic and other polyunsaturated fatty acids in pregnant women. (PMID:21106917)
• Not being breastfed conferred an 8- to 9-point disadvantage in cognition among children GG homozygote for rs174468 (low FADS1 activity) but not among those with the A allele. (PMID:21383846)
• This study shows that genetic variation in the FADS gene cluster (in particular rs174547) can alter desaturase activity in subjects of Caucasians and Asian descent. (PMID:21414826)
• rs174556 in FADS1 gene and rs174617 in FADS2 gene may not be associated with paranoid schizophrenia. (PMID:21560298)
• assessed whether dietary linoleic acid or alpha-linolenic acid modulate the association between the FADS1 rs174546 polymorphism and concentrations of PUFA, other lipids, and lipoproteins in adolescents (PMID:21593353)
• impact of FADS genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA (PMID:21599946)
• increased expression of fatty acid Delta5- and Delta6-desaturases in cystic fibrosis correlated with selective abnormalities in essential fatty acid concentrations (PMID:21605700)
• These results confirm associations of age-related macular degeneration with variants near the TIMP3 gene and at loci involved in HDL metabolism (PMID:21613373)
• genetic association studies in African Americans and European Americans: Seven SNP in FADS gene cluster are associated with plasma omega-6/omega-3 fatty acids; data suggest ethnic differences in synthesis of long-chain polyunsaturated fatty acids. (PMID:21733300)
• The association between dietary intake of fatty acids and allergic diseases might be modulated by FADS gene variants in children. (PMID:21793953)
• Correlation coefficients were estimated to describe fatty acid tracking over 4 years and to assess the influence of FADS variants on tracking. (PMID:21818279)
• rs174556 in the FADS1 gene is very likely to be associated with coronary artery disease in the Chinese Han population (PMID:21917437)
• Report relationship of serum fatty acid composition and desaturase activity to C-reactive protein in Japanese men and women. (PMID:22153152)
• rs174547 in FADS1 may contribute to the susceptibility of CHD by altering HDL-C and TG levels in Chinese individuals. (PMID:22490578)
• discovery and function of a novel FADS1 splice variant (PMID:22619218)
• Total cholesterol, HDL, LDL and triglyceride concentrations may be influenced by the FADS1 FADS2 genotype already in 10 year old children. (PMID:22629455)
• A single nucleotide polymorphism and a haplotype in intron 1 of FADS2 were significantly associated with FADS1 expression. (PMID:22748975)
• genetic association study in maternal/child dyads in England: Data suggest that SNPs in FADS1 (and in FADS2/FADS3) influence fetal fatty acid metabolism; both maternal and child FADS genotypes/haplotypes influence cord plasma long-chain fatty acids. (PMID:22877655)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fads1	ENSMUSG00000010663
rattus_norvegicus	Fads1	ENSRNOG00000020480
caenorhabditis_elegans		WBGENE00001395
caenorhabditis_elegans		WBGENE00001396

Paralogs (3): FADS2 (ENSG00000134824), FADS6 (ENSG00000172782), FADS3 (ENSG00000221968)

Protein

Protein identifiers

Acyl-CoA (8-3)-desaturase — O60427 (reviewed: O60427)

Alternative names: Delta(5) fatty acid desaturase, Fatty acid desaturase 1

All UniProt accessions (17): O60427, A0A0A0MR51, C9J425, C9JJB3, F5GWE3, F5GYH4, F5H0Y2, F5H1Q7, F5H2H3, F5H2R9, F5H3P6, F5H3U5, F5H5X5, F5H852, F5H8G5, H0YB97, H7C2V0

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a front-end fatty acyl-coenzyme A (CoA) desaturase that introduces a cis double bond at carbon 5 located between a preexisting double bond and the carboxyl end of the fatty acyl chain. Involved in biosynthesis of highly unsaturated fatty acids (HUFA) from the essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3) precursors. Specifically, desaturates dihomo-gamma-linoleoate (DGLA) (20:3n-6) and eicosatetraenoate (ETA) (20:4n-3) to generate arachidonate (AA) (20:4n-6) and eicosapentaenoate (EPA) (20:5n-3), respectively. As a rate limiting enzyme for DGLA (20:3n-6) and AA (20:4n-6)-derived eicosanoid biosynthesis, controls the metabolism of inflammatory lipids like prostaglandin E2, critical for efficient acute inflammatory response and maintenance of epithelium homeostasis. Contributes to membrane phospholipid biosynthesis by providing AA (20:4n-6) as a major acyl chain esterified into phospholipids. In particular, regulates phosphatidylinositol-4,5-bisphosphate levels, modulating inflammatory cytokine production in T-cells. Also desaturates (11E)-octadecenoate (trans-vaccenoate)(18:1n-9), a metabolite in the biohydrogenation pathway of LA (18:2n-6). Does not exhibit any catalytic activity toward 20:3n-6, but it may enhance FADS2 activity.

Subcellular location. Endoplasmic reticulum membrane. Mitochondrion Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed, with highest levels in liver, brain, adrenal gland and heart. Highly expressed in fetal liver and brain.

Domain organisation. The histidine box domains may contain the active site and/or be involved in metal ion binding.

Induction. Strongly down-regulated upon differentiation in a neuroblastoma cell line (at protein level).

Pathway. Lipid metabolism; polyunsaturated fatty acid biosynthesis.

Similarity. Belongs to the fatty acid desaturase type 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O60427-1	1, FADS1CS	yes
O60427-2	2, FADS1AT1

RefSeq proteins (1): NP_037534* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001199	Cyt_B5-like_heme/steroid-bd	Domain
IPR005804	FA_desaturase_dom	Domain
IPR012171	Fatty_acid_desaturase	Family
IPR036400	Cyt_B5-like_heme/steroid_sf	Homologous_superfamily

Pfam: PF00173, PF00487

Enzyme classification (BRENDA):

• EC 1.14.19.30 — acyl-lipid (8-3)-desaturase (BRENDA: 22 organisms, 30 substrates, 39 inhibitors, 2 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
(8Z,11Z,14Z)-ICOSA-8,11,14-TRIENOYL-[GLYCEROLIPI	0.056	1
DIHOMO-GAMMA-LINOLENIC ACID	0.0245	1

Catalyzed reactions (Rhea), 3 shown:

• (11E)-octadecenoyl-CoA + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = (5Z,11E)-octadecadienoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (RHEA:46060)
• (8Z,11Z,14Z,17Z)-eicosatetraenoyl-CoA + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (RHEA:46420)
• (8Z,11Z,14Z)-eicosatrienoyl-CoA + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = (5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (RHEA:46424)

UniProt features (31 total): sequence conflict 14, topological domain 5, transmembrane region 4, short sequence motif 3, chain 1, domain 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60427-F1	94.82	0.91

Functional residue map

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

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-2046105	Linoleic acid (LA) metabolism
R-HSA-2046106	alpha-linolenic acid (ALA) metabolism

MSigDB gene sets: 386 (showing top): MODULE_93, MODULE_52, GCM_MAP4K4, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, JI_RESPONSE_TO_FSH_UP, GCM_PTPRD, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, MODULE_45, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MODULE_128

GO Biological Process (14): regulation of DNA-templated transcription (GO:0006355), lipid metabolic process (GO:0006629), unsaturated fatty acid biosynthetic process (GO:0006636), cell-cell signaling (GO:0007267), phospholipid biosynthetic process (GO:0008654), cellular response to starvation (GO:0009267), alpha-linolenic acid metabolic process (GO:0036109), long-chain fatty acid biosynthetic process (GO:0042759), linoleic acid metabolic process (GO:0043651), regulation of cell differentiation (GO:0045595), icosanoid biosynthetic process (GO:0046456), fatty acid metabolic process (GO:0006631), fatty acid biosynthetic process (GO:0006633), fatty acid derivative biosynthetic process (GO:1901570)

GO Molecular Function (6): C-5 sterol desaturase activity (GO:0000248), acyl-CoA 6-desaturase activity (GO:0016213), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on paired donors, with oxidation of a pair of donors resulting in the reduction of molecular oxygen to two molecules of water (GO:0016717), omega-6 fatty acid desaturase activity (GO:0045485), acyl-CoA (8-3)-desaturase activity (GO:0062076)

GO Cellular Component (5): mitochondrion (GO:0005739), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), intracellular membrane-bounded organelle (GO:0043231), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	2
Regulation of lipid metabolism by PPARalpha	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
unsaturated fatty acid metabolic process	3
lipid biosynthetic process	3
long-chain fatty acid metabolic process	3
fatty acid biosynthetic process	2
olefinic compound metabolic process	2
acyl-CoA desaturase activity	2
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	2
cytoplasm	2
intracellular membrane-bounded organelle	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
primary metabolic process	1
cell communication	1
signaling	1
phospholipid metabolic process	1
organophosphate biosynthetic process	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
cell differentiation	1
regulation of developmental process	1
regulation of cellular process	1
icosanoid metabolic process	1
carboxylic acid biosynthetic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
monocarboxylic acid biosynthetic process	1
fatty acid derivative metabolic process	1
sterol desaturase activity	1
catalytic activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
intracellular anatomical structure	1
membrane-bounded organelle	1
intracellular organelle	1
endomembrane system	1

Protein interactions and networks

STRING

1204 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FADS1	SC5D	O75845	958
FADS1	SCD	O00767	948
FADS1	ELOVL5	Q9NYP7	817
FADS1	EBP	Q15125	814
FADS1	ELOVL2	Q9NXB9	756
FADS1	ELOVL6	Q9H5J4	686
FADS1	FASN	P49327	603
FADS1	ELOVL1	Q9BW60	583
FADS1	ELOVL4	Q9GZR5	571
FADS1	ELOVL3	Q9HB03	569
FADS1	SREBF1	P36956	564
FADS1	SCD5	Q86SK9	550
FADS1	PPARA	Q07869	508
FADS1	INS	P01308	506
FADS1	DGAT1	O75907	502

IntAct

100 interactions, top by confidence:

A	B	Type	Score
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
GPR21	TMEM120B	psi-mi:“MI:0914”(association)	0.530
HTR2C	KLRG2	psi-mi:“MI:0914”(association)	0.530
GABRE	FZD6	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
KCNA2	FADS1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
FADS1	HARS2	psi-mi:“MI:0915”(physical association)	0.400
CCDC22	VPS26C	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
PSEN1	PGRMC1	psi-mi:“MI:0914”(association)	0.350
VMP1	TPM3	psi-mi:“MI:0914”(association)	0.350
GP	IPO5	psi-mi:“MI:0914”(association)	0.350
TMCO3	POTEF	psi-mi:“MI:0914”(association)	0.350
SLC39A12	POM121C	psi-mi:“MI:0914”(association)	0.350
SLC18A1	LIMK2	psi-mi:“MI:0914”(association)	0.350
TACR1	GPR89A	psi-mi:“MI:0914”(association)	0.350
GRPR	GPR89A	psi-mi:“MI:0914”(association)	0.350
IL17RC	C2CD2L	psi-mi:“MI:0914”(association)	0.350
PTH1R	DEGS1	psi-mi:“MI:0914”(association)	0.350
SIRT2	DEGS1	psi-mi:“MI:0914”(association)	0.350
FADS1	ASPSCR1	psi-mi:“MI:0914”(association)	0.350
FGFR1	FADS1	psi-mi:“MI:0914”(association)	0.350
EIF3G	EIF3CL	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
TSPAN15	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (119): FADS1 (Affinity Capture-MS), FADS1 (Affinity Capture-MS), FADS1 (Affinity Capture-MS), FADS1 (Affinity Capture-MS), FADS1 (Affinity Capture-MS), FADS1 (Affinity Capture-MS), RNF181 (Affinity Capture-MS), FADS1 (Affinity Capture-MS), FADS1 (Affinity Capture-MS), FADS1 (Affinity Capture-MS), FADS1 (Affinity Capture-MS), UQCC1 (Affinity Capture-MS), FADS1 (Affinity Capture-MS), FADS1 (Affinity Capture-MS), ASPSCR1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0C5PRW9, A0A0C5Q309, A4FV48, A4IFP3, A4UVI1, A8MWK0, A9SIZ6, B2KKL4, B7SB91, B8R1K0, D8X2C5, G5ED44, G5EG11, G5EGN2, O04353, O44390, O60427, O74212, O95864, P07308, P13011, P13516, P32291, Q0VAX3, Q23221, Q3EBF7, Q43469, Q4R749, Q5REA7, Q64420, Q6DDK2, Q6P7B9, Q6T707, Q79EF1, Q86SK9, Q8ISS3, Q8K1P9, Q8S3C1, Q92038, Q920L1

Diamond homologs: A0A0C5PRW9, A4FV48, A4IFP3, A4UVI1, A8MWK0, B2KKL4, B7GCG7, B8MKR3, B8R1K0, C8VJR5, D8X2C5, O04354, O22704, O43169, O48845, O60427, O74875, O94391, O95864, P00167, P00168, P00169, P00170, P00171, P00172, P00173, P00174, P00175, P04166, P09437, P32953, P40312, P40934, P49096, P49097, P49098, P49099, P49100, P56395, P82291

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FADS1	“down-regulates quantity”	“long-chain fatty acyl-CoA(4-)”	“chemical modification”
FADS1	“up-regulates quantity”	arachidonoyl-CoA	“chemical modification”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 129 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SLC-mediated transmembrane transport	10	6.8×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	5	14.5×	7e-03
phospholipase C-activating G protein-coupled receptor signaling pathway	9	10.2×	2e-04
positive regulation of cytosolic calcium ion concentration	8	8.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2307 predictions. Top by Δscore:

Variant	Effect	Δscore
11:61802350:C:A	donor_gain	1.0000
11:61802799:A:AC	donor_gain	1.0000
11:61802800:C:CG	donor_gain	1.0000
11:61802800:CTGG:C	donor_gain	1.0000
11:61802922:AAAGA:A	acceptor_gain	1.0000
11:61802923:AAGA:A	acceptor_gain	1.0000
11:61802924:AGA:A	acceptor_gain	1.0000
11:61802925:GA:G	acceptor_gain	1.0000
11:61802927:C:CC	acceptor_gain	1.0000
11:61802928:T:C	acceptor_gain	1.0000
11:61803026:A:AC	donor_gain	1.0000
11:61803027:C:CC	donor_gain	1.0000
11:61803027:CTCA:C	donor_gain	1.0000
11:61803028:TCA:T	donor_loss	1.0000
11:61803029:CA:C	donor_loss	1.0000
11:61803030:A:AC	donor_gain	1.0000
11:61803030:AC:A	donor_loss	1.0000
11:61803031:C:CT	donor_gain	1.0000
11:61803031:CT:C	donor_gain	1.0000
11:61803031:CTG:C	donor_gain	1.0000
11:61803031:CTGG:C	donor_gain	1.0000
11:61803031:CTGGT:C	donor_gain	1.0000
11:61803112:C:CC	acceptor_gain	1.0000
11:61803116:C:CT	acceptor_gain	1.0000
11:61803117:G:T	acceptor_gain	1.0000
11:61806662:A:AC	donor_gain	1.0000
11:61806663:C:CC	donor_gain	1.0000
11:61810746:CGCA:C	donor_loss	1.0000
11:61810747:GCACC:G	donor_loss	1.0000
11:61810748:CA:C	donor_loss	1.0000

AlphaMissense

3315 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008217 (11:61804925 C>G), RS1000036922 (11:61804461 C>G,T), RS1000076529 (11:61813107 C>A,G,T), RS1000105270 (11:61803121 A>C,G), RS1000190245 (11:61818959 C>T), RS1000304841 (11:61817350 G>T), RS1000549264 (11:61811489 A>C), RS1000571303 (11:61817366 G>A), RS1001170991 (11:61810384 A>G), RS1001357021 (11:61818252 G>A), RS1001467762 (11:61805416 G>A), RS1001627411 (11:61812329 C>T), RS1001746396 (11:61818565 C>T), RS1001820259 (11:61818044 G>A), RS1001867383 (11:61813994 T>A,C)

Disease associations

OMIM: gene MIM:606148 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

310 associations (top):

Study	Trait	p-value
GCST000274_2	Metabolite levels	5.000000e-08
GCST000283_3	LDL cholesterol	1.000000e-07
GCST000286_8	Triglycerides	2.000000e-14
GCST000290_6	HDL cholesterol	2.000000e-12
GCST000550_3	Metabolite levels	7.000000e-179
GCST000568_12	Fasting blood glucose	2.000000e-15
GCST000635_2	Response to statin therapy	7.000000e-06
GCST000635_4	Response to statin therapy	3.000000e-06
GCST000731_4	Resting heart rate	2.000000e-09
GCST000753_2	Metabolic syndrome	6.000000e-07
GCST000755_2	HDL cholesterol	2.000000e-22
GCST000758_8	Triglycerides	5.000000e-24
GCST000759_17	LDL cholesterol	1.000000e-21
GCST000760_25	Cholesterol, total	2.000000e-22
GCST000805_7	HDL cholesterol	1.000000e-12
GCST000809_9	Triglycerides	5.000000e-14
GCST000879_40	Crohn’s disease	2.000000e-11
GCST001178_3	Plasma omega-3 polyunsaturated fatty acid level (eicosapentaenoic acid)	1.000000e-57
GCST001179_18	Plasma omega-3 polyunsaturated fatty acid levels (docosapentaenoic acid)	4.000000e-154
GCST001180_9	Plasma omega-3 polyunsaturated fatty acid levels (alphalinolenic acid)	3.000000e-64
GCST001217_13	Metabolic traits	9.000000e-116
GCST001276_10	Liver enzyme levels (alkaline phosphatase)	3.000000e-09
GCST001392_7	Lipid metabolism phenotypes	8.000000e-262
GCST001413_3	Sphingolipid levels	2.000000e-14
GCST001414_10	Phospholipid levels (plasma)	1.000000e-203
GCST001527_27	Fasting blood glucose (BMI interaction)	2.000000e-09
GCST001639_25	Metabolite levels	4.000000e-264
GCST001656_1	Comprehensive strength and appendicular lean mass	8.000000e-07
GCST001656_2	Comprehensive strength and appendicular lean mass	2.000000e-07
GCST001725_11	Inflammatory bowel disease	2.000000e-15

EFO canonical traits (64, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004725	metabolite measurement
EFO:0000195	metabolic syndrome
EFO:0004574	total cholesterol measurement
EFO:0007760	eicosapentaenoic acid measurement
EFO:0006809	docosapentaenoic acid measurement
EFO:0007759	alpha-linolenic acid measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0004529	lipid measurement
EFO:0004340	body mass index
EFO:0004723	coronary artery calcification
EFO:0004515	muscle measurement
EFO:0004979	comprehensive strength index
EFO:0005128	albumin:globulin ratio measurement
EFO:0004471	insulin sensitivity measurement
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0006810	oleic acid measurement
EFO:0006808	arachidonic acid measurement
EFO:0006807	linoleic acid measurement
EFO:0006811	linolenic acid measurement
EFO:0004458	C-reactive protein measurement
EFO:0007975	gondoic acid measurement
EFO:0007973	palmitoleic acid measurement
EFO:0007974	vaccenic acid measurement
EFO:0004309	platelet count
EFO:0004842	eosinophil count
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5840 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs174541	FADS1, FEN1, MIR611, TMEM258		0.00	0

Binding affinities (BindingDB)

259 measured of 270 human assays (270 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
7-chloro-8-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)pyrazol-4-yl]-2-(trifluoromethyl)pyrido[1,2-a]pyrimidin-4-one	IC50	1.2 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
Ethyl(4-oxo-3-(1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-8-yl)carbamyl fluoride	IC50	1.6 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-methyl-3-(4-(2,2,2- trifluoroethoxy)phenyl)-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin-4-one	IC50	2.7 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(4-(((1R)-2,2-Difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one and 3-(4-(((1S)-2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one	IC50	2.7 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(4- (cyclopropylmethoxy)phenyl)- 8-(methyloxy-d3)-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin-4-one	IC50	3.2 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-methoxy-3-(4-(2,2,2- trifluoroethoxy)phenyl)-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin-4-one	IC50	3.4 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-methoxy-3-(4- propylphenyl)-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin-4-one	IC50	3.6 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-[1-(2,2,3,3,3- pentafluoropropyl)- 1H-pyrazol-4-yl]- 2- (trifluoromethyl)- 4H-pyrazino[1,2- a]pyrimidin-4-one	IC50	3.7 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
7-Chloro-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one	IC50	3.8 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-(methyl-d3)-3-(4- (2,2,2- trifluoroethoxy)phenyl)- 2-(trifluoromethyl)- 4H-pyrido[1,2- a]pyrimidin-4-one	IC50	3.9 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-(methyloxy-d3)- 3-(4-(2,2,2- trifluoroethoxy) phenyl)-2- (trifluoromethyl)- 4H-pyrido[1,2- a]pyrimidin-4-one	IC50	4 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-Methoxy-3-(4-(2,2,3,3,3-pentafluoropropoxy)phenyl)-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one	IC50	4 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-chloro-3-(4-(2,2,2- trifluoroethoxy)phenyl)- 2-(trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin- 4-one	IC50	4.1 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
7-fluoro-8- methoxy-3-[4- (2,2,2- trifluoroethoxy) phenyl]-2- (trifluoromethyl)- 4H-pyrido[1,2- a]pyrimidin-4-one	IC50	4.1 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-{1-[(3,3- difluorocyclobutyl) methyl]-1H- pyrazol-4-yl}-8- methoxy-2- (trifluoromethyl)- 4H-pyrido[1,2- a]pyrimidin-4-one	IC50	4.6 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-{1-[(2,2- difluorocyclopropyl) methyl]-1H- pyrazol-4-yl}-7- fluoro-8-methoxy- 2- (trifluoromethyl)- 4H-pyrido[1,2- a]pyrimidin-4-one	IC50	5 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(3-fluoro-4-(2,2,2- trifluoroethoxy)phenyl)-8- methoxy-(trifluoromethyl)- 4H-pyrido[1,2-a]pyrimidin- 4-one	IC50	5.1 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(4-(cyclopropyl- methoxy)phenyl)-8- methoxy-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin- 4-one	IC50	5.1 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
4-oxo-3-(4-(2,2,2- trifluoroethoxy) phenyl)-2- (trifluoromethyl)- 4H-pyrido[1,2- a]pyrimidine-8- carboxamide	IC50	5.2 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-methoxy-3-(1-phenyl-1H- pyrazol-4-yl)-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin-4-one	IC50	5.4 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-methoxy-3-(4- (trifluoromethoxy)phenyl)-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin-4-one	IC50	5.4 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(4-(2,2- difluoroethoxy)phenyl)-8- (methyloxy-d3)-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin-4-one	IC50	5.6 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-(hydroxymethyl)-3-(4- (2,2,2- trifluoroethoxy)phenyl)- 2-(trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin- 4-one	IC50	5.6 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(4-(((1R)-2,2-Difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one and 3-(4-(((1S)-2,2-difluorocyclopropyl)methoxy)phenyl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one	IC50	5.7 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
(4-(8-Methoxy-4-oxo-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-3-yl)phenoxy)acetonitrile	IC50	5.8 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(2-fluoro-4- (trifluoromethoxy)phenyl)- 8-methoxy-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin-4- one	IC50	5.9 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-methoxy-3-[1- (2,2,3,3,3- pentafluoropropyl)- 1H-pyrazol-4-yl]- 2- (trifluoromethyl)- 4H- [1,3]diazino[1,6- a]pyrimidin-4-one	IC50	6.3 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-acetyl-3-(4-(2,2,2- trifluoroethoxy)phenyl)-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin- 4-one	IC50	6.4 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
2-ethyl-8-methoxy-3-(4- (2,2,2- trifluoroethoxy)phenyl)-4H- pyrido[1,2-a]pyrimidin-4-one	IC50	6.6 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(4- (difluoromethoxy)phenyl)-8- methoxy-2-(trifluoromethyl)- 4H-pyrido[1,2-a]pyrimidin- 4-one	IC50	6.6 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(4-((2,2-difluorocyclo- propyl)methoxy)phenyl)- 8-methoxy-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin- 4-one	IC50	6.6 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-amino-3-(4- (2,2,2- trifluoroeth- oxy)phenyl)-2- (trifluoromethyl)- 4H-pyrido[1,2- a]pyrimidin- 4-one	IC50	6.8 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-methoxy-2- (trifluoromethyl)- 3-[1-(3,3,3- trifluoropropyl)- 1H-pyrazol-4-yl]- 4H-pyrimido[1,2- b]pyridazin-4-one	IC50	6.9 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-(methylamino)-3-(4- (2,2,2- trifluoroethoxy)phenyl)- 2-(trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin- 4-one	IC50	7 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(4-(2,2- difluoroethoxy)phenyl)-8- methoxy-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin-4- one	IC50	7.9 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-chloro-3-(1- (2,2,3,3,3- pentafluoropropyl)- 1H-pyrazol-4-yl)-2- (trifluoromethyl)-4H- pyrido[1,2- a]pyrimidin-4-one	IC50	8.2 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(2-fluoro-4-(2,2,2- trifluoroethoxy)phenyl)-8- methoxy-2-(trifluoromethyl)- 4H- pyrimido[1,2-a]pyrimidin- 4-one	IC50	8.5 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-Methoxy-2-(trifluoromethyl)-3-[3-(3,3,3-trifluoropropyl)-1,2-oxazol-5-yl]-4H-pyrido[1,2-a]pyrimidin-4-one	IC50	8.7 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(2-fluoro-4-(2,2,2- trifluoroethoxy)phenyl)- 8-methoxy-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin- 4-one	IC50	8.9 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-[1-(2,2,3,3,3- pentafluoropropyl)- 1H-pyrazol-4-yl]- 2- (trifluoromethyl)- 4H-pyrido[1,2- a]pyrimidin-4-one	IC50	8.9 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-(fluoromethyl)-3-(4- (2,2,2- trifluoroethoxy)phenyl)- 2-(trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin- 4-one	IC50	9.4 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
2-(difluoromethyl)- 3-(3-fluoro-4-(2,2,2- trifluoroethoxy)phenyl)- 8-methoxy-4H- pyrido[1,2-a]pyrimidin- 4-one	IC50	9.9 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-(Fluoromethoxy)-3-[1-(2,2,3,3,3-pentafluoropropyl)-1H-pyrazol-4-yl]-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one	IC50	10.1 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(4-(2,2,2- trifluoroethoxy)phenyl)-2- (trifluoromethyl)- 4H-pyrido[1,2- a]pyrimidin-4-one	IC50	10.4 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-(methylsulfanyl)-3-(4- (2,2,2- trifluoroethoxy)phenyl)-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin- 4-one	IC50	10.4 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(1-{[(1S)-2,2-Difluorocyclopropyl]methyl}-1H-pyrazol-4-yl)-8-methoxy-2-(trifluoromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one	IC50	10.5 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
2-cyclopropyl-8-methoxy-3- (4-(2,2,2- trifluoroethoxy)phenyl)-4H- pyrido[1,2-a]pyrimidin-4-one	IC50	10.9 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-methoxy-3-[4-(2,2,3,3-tetrafluoropropoxy)phenyl]-2-(trifluoromethyl)pyrido[1,2-a]pyrimidin-4-one	IC50	11.1 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
3-(4-(2,2- difluoropropoxy)phenyl)- 8-methoxy-2- (trifluoromethyl)-4H- pyrido[1,2-a]pyrimidin-4- one	IC50	11.3 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use
8-(methyloxy-d3)-2- (trifluoromethyl)-3-(1-(3,3,3- trifluoropropyl)-1H-pyrazol- 4-yl)-4H- pyrido[1,2-a]pyrimidin-4-one	IC50	11.4 nM	US-12473289: Heterocyclic compounds as delta-5 desaturase inhibitors and methods of use

ChEMBL bioactivities

49 potent at pChembl≥5 of 49 total, top 49 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.28	IC50	0.52	nM	CHEMBL4084502
8.96	IC50	1.1	nM	CHEMBL4856454
8.92	IC50	1.2	nM	CHEMBL4879015
8.82	IC50	1.5	nM	CHEMBL4064555
8.82	IC50	1.5	nM	CHEMBL5278664
8.80	IC50	1.6	nM	CHEMBL4874614
8.77	IC50	1.7	nM	CHEMBL4872983
8.72	IC50	1.9	nM	CHEMBL4439992
8.68	IC50	2.1	nM	CHEMBL4855704
8.62	IC50	2.4	nM	CHEMBL4868627
8.43	IC50	3.7	nM	CHEMBL4102458
8.39	IC50	4.1	nM	CHEMBL4060775
8.30	IC50	5	nM	CHEMBL3608796
8.22	IC50	6	nM	CHEMBL3608798
8.10	IC50	8	nM	CHEMBL3608800
8.06	IC50	8.7	nM	CHEMBL4070383
8.05	IC50	8.9	nM	CHEMBL4070383
7.96	IC50	11	nM	CHEMBL329672
7.82	IC50	15	nM	CHEMBL3608697
7.77	IC50	17	nM	CHEMBL3608700
7.75	IC50	18	nM	CHEMBL3608699
7.75	IC50	18	nM	CHEMBL4090490
7.68	IC50	21	nM	CHEMBL3608797
7.54	IC50	29	nM	CHEMBL2263368
7.47	IC50	34	nM	CHEMBL3608696
7.30	IC50	50	nM	CHEMBL3608702
7.26	IC50	55	nM	CHEMBL4104260
7.24	IC50	58	nM	CHEMBL2263368
7.24	IC50	58	nM	CHEMBL3608795
7.23	IC50	59	nM	CHEMBL3608794
7.22	IC50	60	nM	CHEMBL4066595
7.17	IC50	67	nM	CHEMBL3608695
7.08	IC50	84	nM	CHEMBL3608793
6.82	IC50	150	nM	CHEMBL4069465
6.81	IC50	155	nM	CHEMBL2263369
6.77	IC50	170	nM	CHEMBL4087912
6.77	IC50	170	nM	CHEMBL4080025
6.76	IC50	174	nM	CHEMBL460481
6.76	IC50	173	nM	CHEMBL3608704
6.72	IC50	190	nM	CHEMBL4085437
6.61	IC50	245	nM	CHEMBL3608803
6.59	IC50	254	nM	CHEMBL3608799
6.58	IC50	260	nM	CHEMBL3608703
6.43	IC50	371	nM	CHEMBL3608701
6.29	IC50	516	nM	CHEMBL3608693
6.07	IC50	843	nM	CHEMBL3608694
6.03	IC50	925	nM	CHEMBL3608698
5.96	IC50	1100	nM	CHEMBL4063561
5.88	IC50	1325	nM	CHEMBL1272304

PubChem BioAssay actives

49 with measured affinity, of 145 total; 47 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-chloro-5-[(4S,5S)-5-(4-fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]benzonitrile	1471516: Inhibition of D5D in human HepG2 cells assessed as [14C]AA formation from [14C]DGLA preincubated for 30 mins followed by [14C]eicosatrienoic acid addition measured after 3 hrs by TLC analysis	ic50	0.0005	uM
7-fluoro-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)pyrazol-4-yl]pyrido[1,2-a]pyrimidin-4-one	1777609: Inhibition of Delta-5-desaturase (unknown origin) expressed in HEK2936E cell membrane incubated for 1 hr by DGLA-CoA and Arachidonyl-CoA mass spectrometric assay	ic50	0.0011	uM
7-chloro-8-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)pyrazol-4-yl]-2-(trifluoromethyl)pyrido[1,2-a]pyrimidin-4-one	1777609: Inhibition of Delta-5-desaturase (unknown origin) expressed in HEK2936E cell membrane incubated for 1 hr by DGLA-CoA and Arachidonyl-CoA mass spectrometric assay	ic50	0.0012	uM
5-[(4S,5S)-5-(4-fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]benzene-1,3-dicarbonitrile	1471516: Inhibition of D5D in human HepG2 cells assessed as [14C]AA formation from [14C]DGLA preincubated for 30 mins followed by [14C]eicosatrienoic acid addition measured after 3 hrs by TLC analysis	ic50	0.0015	uM
5-[(4R,5R)-5-(4-fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]benzene-1,3-dicarbonitrile	1956605: Inhibition of human Delta 5 desaturase (unknown origin) expressed in human HepG2 cells	ic50	0.0015	uM
N-methyl-N-[4-oxo-3-[1-(2,2,3,3,3-pentafluoropropyl)pyrazol-4-yl]-2-(trifluoromethyl)pyrido[1,2-a]pyrimidin-8-yl]carbamoyl fluoride	1777609: Inhibition of Delta-5-desaturase (unknown origin) expressed in HEK2936E cell membrane incubated for 1 hr by DGLA-CoA and Arachidonyl-CoA mass spectrometric assay	ic50	0.0016	uM
7-methyl-3-[1-(2,2,3,3,3-pentafluoropropyl)pyrazol-4-yl]-2-(trifluoromethyl)pyrido[1,2-a]pyrimidin-4-one	1777609: Inhibition of Delta-5-desaturase (unknown origin) expressed in HEK2936E cell membrane incubated for 1 hr by DGLA-CoA and Arachidonyl-CoA mass spectrometric assay	ic50	0.0017	uM
N-[2-[4-oxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]thieno[3,4-d]pyrimidin-2-yl]sulfanylethyl]acetamide	1633012: Inhibition of D5D in human HepG2 cells using [14C]DGLA as substrate preincubated for 30 mins followed by substrate addition measured after 3 hrs	ic50	0.0019	uM
7-fluoro-3-[1-(2,2,3,3,3-pentafluoropropyl)pyrazol-4-yl]-2-(trifluoromethyl)pyrido[1,2-a]pyrimidin-4-one	1777609: Inhibition of Delta-5-desaturase (unknown origin) expressed in HEK2936E cell membrane incubated for 1 hr by DGLA-CoA and Arachidonyl-CoA mass spectrometric assay	ic50	0.0021	uM
7-chloro-2-(trifluoromethyl)-3-[1-(3,3,3-trifluoropropyl)pyrazol-4-yl]pyrido[1,2-a]pyrimidin-4-one	1777609: Inhibition of Delta-5-desaturase (unknown origin) expressed in HEK2936E cell membrane incubated for 1 hr by DGLA-CoA and Arachidonyl-CoA mass spectrometric assay	ic50	0.0024	uM
3-fluoro-5-[(4S,5S)-5-(4-fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]benzonitrile	1471516: Inhibition of D5D in human HepG2 cells assessed as [14C]AA formation from [14C]DGLA preincubated for 30 mins followed by [14C]eicosatrienoic acid addition measured after 3 hrs by TLC analysis	ic50	0.0037	uM
5-(4-fluorophenyl)-3-(3-methoxyphenyl)-1,3-oxazolidin-2-one	1471516: Inhibition of D5D in human HepG2 cells assessed as [14C]AA formation from [14C]DGLA preincubated for 30 mins followed by [14C]eicosatrienoic acid addition measured after 3 hrs by TLC analysis	ic50	0.0041	uM
5-chloro-N-(3-chlorophenyl)-1H-indazol-3-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.0050	uM
N-(3-chlorophenyl)-5-methyl-1H-indazol-3-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.0060	uM
N-(3-chlorophenyl)-5-methoxy-1H-indazol-3-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.0080	uM
3-[(4S,5S)-5-(4-fluorophenyl)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]benzonitrile	1471516: Inhibition of D5D in human HepG2 cells assessed as [14C]AA formation from [14C]DGLA preincubated for 30 mins followed by [14C]eicosatrienoic acid addition measured after 3 hrs by TLC analysis	ic50	0.0087	uM
N-(3-chlorophenyl)quinazolin-4-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.0110	uM
N-(3-chlorophenyl)-2-hydroxy-5-methoxybenzamide	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.0150	uM
N-(3-chlorophenyl)naphthalen-1-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.0170	uM
3-(2,5-dimethoxyphenyl)-5-(4-fluorophenyl)-1,3-oxazolidin-2-one	1471516: Inhibition of D5D in human HepG2 cells assessed as [14C]AA formation from [14C]DGLA preincubated for 30 mins followed by [14C]eicosatrienoic acid addition measured after 3 hrs by TLC analysis	ic50	0.0180	uM
N-(3-chlorophenyl)quinolin-4-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.0180	uM
5-bromo-N-(3-chlorophenyl)-1H-indazol-3-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.0210	uM
2-amino-N-(3-chlorophenyl)benzamide	1633012: Inhibition of D5D in human HepG2 cells using [14C]DGLA as substrate preincubated for 30 mins followed by substrate addition measured after 3 hrs	ic50	0.0290	uM
2-amino-5-chloro-N-(3-chlorophenyl)benzamide	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.0340	uM
N-(3-chlorophenyl)thieno[3,2-d]pyrimidin-4-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.0500	uM
3-(3-chlorophenyl)-5-(4-fluorophenyl)-1,3-oxazolidin-2-one	1471516: Inhibition of D5D in human HepG2 cells assessed as [14C]AA formation from [14C]DGLA preincubated for 30 mins followed by [14C]eicosatrienoic acid addition measured after 3 hrs by TLC analysis	ic50	0.0550	uM
N-(3-chlorophenyl)-5-fluoro-1H-indazol-3-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.0580	uM
N-(3-fluorophenyl)-1H-indazol-3-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.0590	uM
3-[(5S)-5-(4-fluorophenyl)-2-oxo-1,3-oxazolidin-3-yl]benzonitrile	1471516: Inhibition of D5D in human HepG2 cells assessed as [14C]AA formation from [14C]DGLA preincubated for 30 mins followed by [14C]eicosatrienoic acid addition measured after 3 hrs by TLC analysis	ic50	0.0600	uM
2-amino-N-(3-chlorophenyl)-5-fluorobenzamide	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.0670	uM
N-(3-chlorophenyl)-1H-indazol-3-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.0840	uM
3-[(2,4-dichlorophenyl)methyl]-5-(4-fluorophenyl)-1,3-oxazolidin-2-one	1471516: Inhibition of D5D in human HepG2 cells assessed as [14C]AA formation from [14C]DGLA preincubated for 30 mins followed by [14C]eicosatrienoic acid addition measured after 3 hrs by TLC analysis	ic50	0.1500	uM
2-amino-N-(3-chloro-4-fluorophenyl)benzamide	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.1550	uM
3-[5-(4-fluorophenyl)-2-oxo-1,3-oxazolidin-3-yl]benzonitrile	1471516: Inhibition of D5D in human HepG2 cells assessed as [14C]AA formation from [14C]DGLA preincubated for 30 mins followed by [14C]eicosatrienoic acid addition measured after 3 hrs by TLC analysis	ic50	0.1700	uM
3-(3-fluorophenyl)-5-(4-fluorophenyl)-1,3-oxazolidin-2-one	1471516: Inhibition of D5D in human HepG2 cells assessed as [14C]AA formation from [14C]DGLA preincubated for 30 mins followed by [14C]eicosatrienoic acid addition measured after 3 hrs by TLC analysis	ic50	0.1700	uM
N-(3-chlorophenyl)-2,3-dihydro-1H-inden-1-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.1730	uM
N-(3-chlorophenyl)-2-hydroxybenzamide	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.1740	uM
5-(4-fluorophenyl)-3-phenyl-1,3-oxazolidin-2-one	1471516: Inhibition of D5D in human HepG2 cells assessed as [14C]AA formation from [14C]DGLA preincubated for 30 mins followed by [14C]eicosatrienoic acid addition measured after 3 hrs by TLC analysis	ic50	0.1900	uM
2-amino-N-(3,5-dichlorophenyl)benzamide	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.2450	uM
N-(3-chlorophenyl)-5-(trifluoromethyl)-1H-indazol-3-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.2540	uM
N-(3-chlorophenyl)thieno[2,3-d]pyrimidin-4-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.2600	uM
N-(3-chlorophenyl)furo[3,2-c]pyridin-4-amine	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.3710	uM
2-amino-N-(3-fluorophenyl)benzamide	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.5160	uM
2-amino-N-(3-propan-2-ylphenyl)benzamide	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.8430	uM
N-(3-chlorophenyl)-5-ethoxy-2-hydroxybenzamide	1243190: Inhibition of liver delta-5 desaturase (unknown origin)	ic50	0.9250	uM
3-[(2,4-dichloro-5-hydroxyphenyl)methyl]-5-phenyl-1,3-oxazolidin-2-one	1471516: Inhibition of D5D in human HepG2 cells assessed as [14C]AA formation from [14C]DGLA preincubated for 30 mins followed by [14C]eicosatrienoic acid addition measured after 3 hrs by TLC analysis	ic50	1.1000	uM
2-[4-(2-fluorophenyl)phenyl]-6-methylsulfonyl-1H-benzimidazole	528143: Inhibition of Delta(5) fatty acid desaturase in human HepG2 cells	ic50	1.3250	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, increases expression	5
Valproic Acid	affects expression, decreases expression, increases methylation	5
Acetaminophen	decreases expression, increases expression	3
Cisplatin	affects cotreatment, increases expression, affects response to substance	3
Tetrachlorodibenzodioxin	decreases expression	3
Tobacco Smoke Pollution	decreases expression, increases expression	3
methylmercuric chloride	increases expression, affects cotreatment	2
lead acetate	increases expression, affects cotreatment, decreases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases expression	2
cobaltous chloride	decreases expression	2
perfluorooctanoic acid	decreases expression, increases expression	2
perfluorooctane sulfonic acid	decreases expression	2
bisphenol S	increases expression, increases methylation	2
Resveratrol	affects cotreatment, increases expression	2
Decitabine	increases expression	2
Fulvestrant	affects cotreatment, increases methylation, decreases reaction, increases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Estradiol	affects cotreatment, increases expression, affects abundance, decreases reaction	2
Methotrexate	affects response to substance, increases expression	2
Testosterone	affects cotreatment, decreases expression, affects abundance, increases expression	2
Cyclosporine	affects expression, decreases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
geraniol	decreases activity, decreases chemical synthesis, decreases metabolic processing	1
25-hydroxycholesterol	decreases reaction, increases expression, decreases expression	1
sodium arsenate	increases expression, increases abundance	1
beta-lapachone	decreases expression	1

ChEMBL screening assays

21 unique, capped per target: 21 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1050578	Binding	Binding affinity to delta-5 saturase in human HepG2 cells by whole cell assay	Thiazole analog as stearoyl-CoA desaturase 1 inhibitor. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_F1UP	HyCyte U-251MG KO-hFADS1	Cancer cell line	Male
CVCL_SM76	HAP1 FADS1 (-) 1	Cancer cell line	Male
CVCL_SM77	HAP1 FADS1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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