FADS2

Summary

FADS2 (fatty acid desaturase 2, HGNC:3575) is a protein-coding gene on chromosome 11q12.2, encoding Acyl-CoA 6-desaturase (O95864). Involved in the 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, acting as a fatty acyl-coenzyme A (CoA) desaturase that introduces a cis….

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 at 11q12-q13.1; this cluster is thought to have arisen evolutionarily from gene duplication based on its similar exon/intron organization. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 9415 — RefSeq curated summary.

At a glance

• GWAS associations: 451
• Clinical variants (ClinVar): 42 total
• Druggable target: yes
• MANE Select transcript: NM_004265

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3575
Approved symbol	FADS2
Name	fatty acid desaturase 2
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	FADSD6, D6D, TU13, DES6, SLL0262
Ensembl gene	ENSG00000134824
Ensembl biotype	protein_coding
OMIM	606149
Entrez	9415

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 15 protein_coding, 6 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000257261, ENST00000278840, ENST00000355484, ENST00000517312, ENST00000517839, ENST00000518606, ENST00000520145, ENST00000521571, ENST00000521849, ENST00000522056, ENST00000522359, ENST00000522639, ENST00000523235, ENST00000543584, ENST00000574708, ENST00000891283, ENST00000891284, ENST00000891285, ENST00000925572, ENST00000925573, ENST00000925574, ENST00000925575, ENST00000925576

RefSeq mRNA: 3 — MANE Select: NM_004265 NM_001281501, NM_001281502, NM_004265

CCDS: CCDS60807, CCDS60808, CCDS8012

Canonical transcript exons

ENST00000278840 — 12 exons

Exon	Start	End
ENSE00000916419	61857011	61857071
ENSE00000916421	61840624	61840725
ENSE00002115984	61865638	61867354
ENSE00002121234	61828300	61828597
ENSE00003512884	61862972	61863069
ENSE00003595503	61837778	61837888
ENSE00003609093	61863282	61863378
ENSE00003609950	61848159	61848284
ENSE00003624132	61865152	61865277
ENSE00003645283	61857454	61857530
ENSE00003684159	61840334	61840531
ENSE00003789323	61863707	61863786

Expression profiles

Bgee: expression breadth ubiquitous, 229 present calls, max score 99.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 113.1541 / max 1557.8104, expressed in 1761 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114621	94.8717	1588
114615	7.0030	1411
114614	3.3599	1276
114620	3.2801	1139
114618	2.1788	1116
114613	0.8605	526
114625	0.5842	311
114616	0.5679	308
114617	0.4481	254

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	99.37	gold quality
right adrenal gland	UBERON:0001233	99.34	gold quality
left adrenal gland cortex	UBERON:0035825	99.15	gold quality
left adrenal gland	UBERON:0001234	99.12	gold quality
adrenal cortex	UBERON:0001235	98.89	gold quality
adrenal gland	UBERON:0002369	98.81	gold quality
ventricular zone	UBERON:0003053	98.71	gold quality
ganglionic eminence	UBERON:0004023	98.71	gold quality
adrenal tissue	UBERON:0018303	98.41	gold quality
stromal cell of endometrium	CL:0002255	98.35	gold quality
cortical plate	UBERON:0005343	97.84	gold quality
upper leg skin	UBERON:0004262	96.88	gold quality
amygdala	UBERON:0001876	96.71	gold quality
hypothalamus	UBERON:0001898	96.62	gold quality
islet of Langerhans	UBERON:0000006	96.56	gold quality
smooth muscle tissue	UBERON:0001135	96.41	gold quality
nucleus accumbens	UBERON:0001882	96.13	gold quality
right frontal lobe	UBERON:0002810	96.03	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.80	gold quality
cingulate cortex	UBERON:0003027	95.74	gold quality
anterior cingulate cortex	UBERON:0009835	95.69	gold quality
caudate nucleus	UBERON:0001873	95.43	gold quality
putamen	UBERON:0001874	95.24	gold quality
spinal cord	UBERON:0002240	95.04	gold quality
ascending aorta	UBERON:0001496	94.98	gold quality
thoracic aorta	UBERON:0001515	94.88	gold quality
embryo	UBERON:0000922	94.81	gold quality
adenohypophysis	UBERON:0002196	94.80	gold quality
body of uterus	UBERON:0009853	94.77	gold quality
middle frontal gyrus	UBERON:0002702	94.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	383.97
E-MTAB-9067	yes	20.70
E-CURD-112	yes	9.14
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1, PITX2, PPARA, SREBF1

miRNA regulators (miRDB)

62 targeting FADS2, 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-4682	100.00	68.89	1258
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-4667-3P	99.26	65.45	1608
HSA-MIR-4784	99.15	67.41	1733

Literature-anchored findings (GeneRIF, showing 40)

• meication of suppression by highly unsaturated fatty acids mediated by E-box like sterol regulatory element (PMID:12147235)
• data indicate that the 5’-flanking region of the human D6D gene contains a DR-1 that functions in the regulation of human D6D gene transcription, and thereby plays a role in the synthesis of 20- and 22-carbon polyenoic fatty acids (PMID:12562861)
• Delta-6 desaturase/FADS2 is the major fatty acid desaturase in human sebaceous glands (PMID:12713571)
• It is concluded that aggressive breast tumours have a reduced level of delta-6-desaturase. This aberrant expression has clinical bearings to the outcome in patients with breast cancer. (PMID:12851727)
• 6-fold decrease in promoter activity in the polymorphic variant FADS2 regulatory region compared with the normal gene, confirming the functional relevance of the insertion mutation to the decreased expression of the gene in the patient-derived cells (PMID:12951357)
• FADS1 FADS2 genetic varients and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids (PMID:16670158)
• These preliminary findings are suggestive of an association between FADS2 and ADHD. (PMID:16893529)
• FABP 2 may have a role in reducing delta 6 desaturase activity and plasma arachidonic acid in obese children (PMID:16908951)
• The realtionship of genetic polymorphisms of FADS2 to alpha-linolenic on the risk of myocardial infarction in Costa Rican patients is reported. (PMID:17284757)
• 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)
• the association between breastfeeding and IQ is moderated by a genetic variant in FADS2, a gene involved in the genetic control of fatty acid pathways (PMID:17984066)
• strong association of FADS2 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)
• ALA concentrations in adipose tissue are associated with lower prevalence of the metabolic syndrome. Lack of association among homozygote carriers of the FADS2 deletion allele suggests that this association may be due to the conversion of ALA into EPA. (PMID:19144731)
• polymorphism rs968567 influences FADS2 gene promoter activity and alters DNA binding affinity of the transcription factor ELK1. (PMID:19546342)
• Single nucleotide polymorphisms (SNPs) in the 2 desaturase encoding gene FADS2 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 FADS2 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 FADS2, and blood levels of polyunsaturated fatty acids have been reported–REVIEW (PMID:20045144)
• 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)
• potential role in disease onset and development (Review) (PMID:20565855)
• This studydemonstrated that FADS2 mRNA expression is significantly and selectively elevated in the prefrontal cortex of bipolar disorder patients (PMID:20615514)
• FADS2 polymorphisms modify the effect of breastfeeding on child IQ. (PMID:20644632)
• 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)
• the fatty acid ratio that reflects D5D activity was inversely associated with risk [0.46 (0.31, 0.70)] of type 2 diabetes. (PMID:20980488)
• 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)
• 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)
• increased expression of fatty acid Delta5- and Delta6-desaturases in cystic fibrosis correlated with selective abnormalities in essential fatty acid concentrations (PMID:21605700)
• the polymorphism rs3834458 does not appear to directly affect FADS2 promoter activity and is not responsible for a previously reported Delta6-desaturase deficiency. (PMID:21629299)
• 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)
• there was no combined effect of the polymorphisms in the FADS1 and FADS2 genes in coronary artery disease in the Chinese Han population (PMID:21917437)
• PTB is shown to bind an exonic splicing silencer element and repress alternative splicing of FADS2 (PMID:21980057)
• The loss of FADS2-encoded activities in cancer cells shuts down normal polyunsaturated fatty acid biosynthesis. (PMID:22140540)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	fads2	ENSDARG00000019532
mus_musculus	Fads2	ENSMUSG00000024665
rattus_norvegicus	Fads2	ENSRNOG00000020440
caenorhabditis_elegans		WBGENE00001395
caenorhabditis_elegans		WBGENE00001396

Paralogs (3): FADS1 (ENSG00000149485), FADS6 (ENSG00000172782), FADS3 (ENSG00000221968)

Protein

Protein identifiers

Acyl-CoA 6-desaturase — O95864 (reviewed: O95864)

Alternative names: Delta(6) fatty acid desaturase, Fatty acid desaturase 2

All UniProt accessions (4): E5RGD8, E5RGZ5, E5RHL3, O95864

UniProt curated annotations — full annotation on UniProt →

Function. Involved in the 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, acting as a fatty acyl-coenzyme A (CoA) desaturase that introduces a cis double bond at carbon 6 of the fatty acyl chain. Catalyzes the first and rate limiting step in this pathway which is the desaturation of LA (18:2n-6) and ALA (18:3n-3) into gamma-linoleate (GLA) (18:3n-6) and stearidonate (18:4n-3), respectively. Subsequently, in the biosynthetic pathway of HUFA n-3 series, it desaturates tetracosapentaenoate (24:5n-3) to tetracosahexaenoate (24:6n-3), which is then converted to docosahexaenoate (DHA)(22:6n-3), an important lipid for nervous system function. Desaturates hexadecanate (palmitate) to produce 6Z-hexadecenoate (sapienate), a fatty acid unique to humans and major component of human sebum, that has been implicated in the development of acne and may have potent antibacterial activity. It can also desaturate (11E)-octadecenoate (trans-vaccenoate, the predominant trans fatty acid in human milk) at carbon 6 generating (6Z,11E)-octadecadienoate. In addition to Delta-6 activity, this enzyme exhibits Delta-8 activity with slight biases toward n-3 fatty acyl-CoA substrates.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in a wide array of tissues, highest expression is found in liver followed by brain, lung, heart, and retina. A lower level is found in breast tumor when compared with normal tissues; lowest levels were found in patients with poor prognostic index.

Domain organisation. The protein sequence includes a number of characteristic features of microsomal fatty acid desaturases including the three histidine boxes HXXXH, HXXHH, and QXXHH (these domains may contain the active site and/or be involved in metal ion binding), and the N-terminal cytochrome b5 domain containing the heme-binding motif, HPGG, similar to that of other fatty acid desaturases.

Induction. Repressed by dietary highly unsaturated fatty acids.

Pathway. Lipid metabolism; polyunsaturated fatty acid biosynthesis.

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

Isoforms (4)

UniProt ID	Names	Canonical?
O95864-1	1	yes
O95864-2	2
O95864-3	3
O95864-4	4

RefSeq proteins (3): NP_001268430, NP_001268431, NP_004256* (*=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 1.14.19.3 — acyl-CoA 6-desaturase (BRENDA: 46 organisms, 69 substrates, 18 inhibitors, 2 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
LINOLEOYL-COA	0.045	1

Catalyzed reactions (Rhea), 7 shown:

• (9Z,12Z,15Z,18Z,21Z)-tetracosapentaenoyl-CoA + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = (6Z,9Z,12Z,15Z,18Z,21Z)-tetracosahexaenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (RHEA:36999)
• hexadecanoyl-CoA + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = (6Z)-hexadecenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (RHEA:37023)
• (11Z,14Z)-eicosadienoyl-CoA + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = (8Z,11Z,14Z)-eicosatrienoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (RHEA:39567)
• (11Z,14Z,17Z)-eicosatrienoyl-CoA + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = (8Z,11Z,14Z,17Z)-eicosatetraenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (RHEA:39571)
• (11E)-octadecenoyl-CoA + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = (6Z,11E)-octadecadienoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (RHEA:46064)
• (9Z,12Z)-octadecadienoyl-CoA + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = (6Z,9Z,12Z)-octadecatrienoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (RHEA:47140)
• (9Z,12Z,15Z)-octadecatrienoyl-CoA + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = (6Z,9Z,12Z,15Z)-octadecatetraenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O (RHEA:47144)

UniProt features (20 total): topological domain 5, transmembrane region 4, short sequence motif 3, splice variant 3, sequence conflict 3, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95864-F1	95.39	0.95

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-2046105	Linoleic acid (LA) metabolism
R-HSA-2046106	alpha-linolenic acid (ALA) metabolism

MSigDB gene sets: 260 (showing top): MODULE_93, MODULE_52, JI_RESPONSE_TO_FSH_UP, GOBP_INFLAMMATORY_RESPONSE, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, MODULE_64, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, MODULE_16, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, KEGG_BIOSYNTHESIS_OF_UNSATURATED_FATTY_ACIDS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, PATIL_LIVER_CANCER, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, MODULE_66

GO Biological Process (10): arachidonate metabolite production involved in inflammatory response (GO:0002538), lipid metabolic process (GO:0006629), unsaturated fatty acid biosynthetic process (GO:0006636), alpha-linolenic acid metabolic process (GO:0036109), long-chain fatty acid biosynthetic process (GO:0042759), linoleic acid metabolic process (GO:0043651), positive regulation of cellular response to oxidative stress (GO:1900409), fatty acid derivative biosynthetic process (GO:1901570), fatty acid metabolic process (GO:0006631), fatty acid biosynthetic process (GO:0006633)

GO Molecular Function (6): stearoyl-CoA 9-desaturase activity (GO:0004768), acyl-CoA 6-desaturase activity (GO:0016213), 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), protein binding (GO:0005515), acyl-CoA desaturase activity (GO:0016215), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), membrane (GO:0016020), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
alpha-linolenic (omega3) and linoleic (omega6) acid metabolism	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
unsaturated fatty acid metabolic process	3
long-chain fatty acid metabolic process	3
fatty acid biosynthetic process	2
olefinic compound metabolic process	2
lipid biosynthetic process	2
acyl-CoA desaturase activity	2
production of molecular mediator involved in inflammatory response	1
primary metabolic process	1
cellular response to oxidative stress	1
positive regulation of cellular process	1
regulation of cellular response to oxidative stress	1
positive regulation of response to oxidative stress	1
fatty acid derivative metabolic process	1
lipid metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
monocarboxylic acid biosynthetic process	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen	1
binding	1
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	1
catalytic activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1156 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FADS2	SCD	O00767	963
FADS2	ELOVL5	Q9NYP7	818
FADS2	ELOVL2	Q9NXB9	756
FADS2	ELOVL6	Q9H5J4	687
FADS2	FASN	P49327	628
FADS2	SREBF1	P36956	623
FADS2	ELOVL1	Q9BW60	611
FADS2	ELOVL4	Q9GZR5	590
FADS2	SCD5	Q86SK9	587
FADS2	ELOVL3	Q9HB03	567
FADS2	DEGS2	Q6QHC5	559
FADS2	ELOVL7	A1L3X0	545
FADS2	PPARA	Q07869	531
FADS2	DGAT1	O75907	515
FADS2	PEMT	Q9UBM1	499
FADS2	DEGS1	O15121	499

IntAct

44 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
	SCD	psi-mi:“MI:0914”(association)	0.500
CCDC110	FADS2	psi-mi:“MI:0915”(physical association)	0.400
CLGN	FADS2	psi-mi:“MI:0915”(physical association)	0.400
FADS2	GPBP1L1	psi-mi:“MI:0915”(physical association)	0.400
LELP1	FADS2	psi-mi:“MI:0915”(physical association)	0.400
SPDL1	FADS2	psi-mi:“MI:0915”(physical association)	0.400
APOB	FADS2	psi-mi:“MI:0915”(physical association)	0.400
FADS2	PANK3	psi-mi:“MI:0915”(physical association)	0.400
	ESYT2	psi-mi:“MI:0914”(association)	0.350
E5	ESYT2	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
	TSPO	psi-mi:“MI:0914”(association)	0.350
NUDCD1	TUBAL3	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
APP	MGST3	psi-mi:“MI:0914”(association)	0.350
PSEN1	PGRMC1	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CD81	STX3	psi-mi:“MI:0914”(association)	0.350
CD81	PVR	psi-mi:“MI:0914”(association)	0.350
	DENND11	psi-mi:“MI:0914”(association)	0.350
PA	DDX39A	psi-mi:“MI:0914”(association)	0.350
M	TM9SF1	psi-mi:“MI:0914”(association)	0.350
SMIM26	ESYT2	psi-mi:“MI:0914”(association)	0.350
FADS3	PEX7	psi-mi:“MI:0914”(association)	0.350
PINK1	A2ML1	psi-mi:“MI:0914”(association)	0.350
SLC19A2	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC22A10	PGRMC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (105): FADS2 (Affinity Capture-MS), FADS2 (Affinity Capture-MS), FADS2 (Affinity Capture-MS), FADS2 (Affinity Capture-MS), FADS2 (Proximity Label-MS), FADS2 (Proximity Label-MS), FADS2 (Affinity Capture-RNA), FADS2 (Affinity Capture-MS), FADS2 (Affinity Capture-MS), FADS2 (Affinity Capture-MS), FADS2 (Affinity Capture-MS), FADS2 (Affinity Capture-MS), FADS2 (Proximity Label-MS), FADS2 (Proximity Label-MS), FADS2 (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
FADS2	“down-regulates quantity”	“long-chain fatty acyl-CoA(4-)”	“chemical modification”
FADS2	“up-regulates quantity”	arachidonoyl-CoA	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

4520 predictions. Top by Δscore:

Variant	Effect	Δscore
11:61795338:TA:T	acceptor_loss	1.0000
11:61795339:A:AG	acceptor_gain	1.0000
11:61795339:AGTCA:A	acceptor_loss	1.0000
11:61795340:G:GG	acceptor_gain	1.0000
11:61795340:GT:G	acceptor_gain	1.0000
11:61795340:GTC:G	acceptor_gain	1.0000
11:61795340:GTCAT:G	acceptor_gain	1.0000
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

AlphaMissense

2980 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:61863782:C:G	H385D	0.999
11:61840636:T:A	W177R	0.998
11:61840636:T:C	W177R	0.998
11:61848177:T:A	W213R	0.998
11:61848177:T:C	W213R	0.998
11:61848179:G:C	W213C	0.998
11:61848179:G:T	W213C	0.998
11:61848189:C:G	H217D	0.998
11:61848191:C:A	H217Q	0.998
11:61848191:C:G	H217Q	0.998
11:61848198:C:G	H220D	0.998
11:61863765:T:C	L379P	0.998
11:61840630:G:C	A175P	0.997
11:61840645:C:G	H180D	0.997
11:61848159:G:C	G207R	0.997
11:61848200:C:A	H220Q	0.997
11:61848200:C:G	H220Q	0.997
11:61857052:G:C	Q262H	0.997
11:61857052:G:T	Q262H	0.997
11:61863292:A:C	S331R	0.997
11:61863294:C:A	S331R	0.997
11:61863294:C:G	S331R	0.997
11:61863298:T:A	W333R	0.997
11:61863298:T:C	W333R	0.997
11:61863327:C:A	H342Q	0.997
11:61863327:C:G	H342Q	0.997
11:61863755:A:C	S376R	0.997
11:61863757:T:A	S376R	0.997
11:61863757:T:G	S376R	0.997
11:61863759:G:A	G377E	0.997

dbSNP variants (sampled 300 via entrez): RS1000027467 (11:61828987 C>T), RS1000068847 (11:61847594 G>A), RS1000085757 (11:61850818 C>T), RS1000190245 (11:61818959 C>T), RS1000219260 (11:61852984 T>C), RS1000271463 (11:61841346 G>A), RS1000287426 (11:61858057 T>C), RS1000304841 (11:61817350 G>T), RS1000525265 (11:61866044 T>A), RS1000556660 (11:61830803 A>G), RS1000571303 (11:61817366 G>A), RS1000630306 (11:61830528 C>T), RS1000786193 (11:61837739 G>A,C), RS1000844322 (11:61863182 C>A), RS1001019042 (11:61831713 A>G)

Disease associations

OMIM: gene MIM:606149 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

451 associations (top):

Study	Trait	p-value
GCST000282_5	LDL cholesterol	4.000000e-13
GCST000283_3	LDL cholesterol	1.000000e-07
GCST000285_8	Cholesterol, total	2.000000e-10
GCST000286_8	Triglycerides	2.000000e-14
GCST000288_1	HDL cholesterol	4.000000e-06
GCST000290_6	HDL cholesterol	2.000000e-12
GCST000635_2	Response to statin therapy	7.000000e-06
GCST000635_4	Response to statin therapy	3.000000e-06
GCST000753_1	Metabolic syndrome	4.000000e-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
GCST001178_4	Plasma omega-3 polyunsaturated fatty acid level (eicosapentaenoic acid)	4.000000e-55
GCST001179_16	Plasma omega-3 polyunsaturated fatty acid levels (docosapentaenoic acid)	3.000000e-152
GCST001180_8	Plasma omega-3 polyunsaturated fatty acid levels (alphalinolenic acid)	3.000000e-63
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
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
GCST001834_5	Oleic acid (18:1n-9) levels	2.000000e-32
GCST001840_3	Stearic acid (18:0) levels	1.000000e-20
GCST001841_1	Palmitoleic acid (16:1n-7) levels	7.000000e-13
GCST001852_1	Metabolite levels	3.000000e-09
GCST002216_25	Triglycerides	7.000000e-38
GCST002221_47	Cholesterol, total	3.000000e-37

EFO canonical traits (73, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0000195	metabolic syndrome
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:0004723	coronary artery calcification
EFO:0004515	muscle measurement
EFO:0004979	comprehensive strength index
EFO:0004471	insulin sensitivity measurement
EFO:0004541	HbA1c measurement
EFO:0005680	omega-6 polyunsaturated fatty acid measurement
EFO:0005094	P wave duration
EFO:0004682	QT interval
EFO:0004461	iron biomarker measurement
EFO:0006341	transferrin 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:0005054	QRS complex
EFO:0007975	gondoic acid measurement
EFO:0007973	palmitoleic acid measurement
EFO:0007974	vaccenic acid measurement
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6097 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.39	Kd	407.6	nM	CHEMBL5653589
6.39	ED50	407.6	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 104 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148357: Binding affinity to human FADS2 incubated for 45 mins by Kinobead based pull down assay	kd	0.4077	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	5
bisphenol A	affects expression, decreases expression, increases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
cobaltous chloride	decreases expression	2
perfluorooctanoic acid	affects expression, decreases expression	2
Sunitinib	increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Amiodarone	decreases reaction, increases expression, affects expression, affects reaction, increases uptake (+1 more)	2
Arsenic	affects cotreatment, decreases expression, increases abundance, decreases ubiquitination	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Cisplatin	affects cotreatment, increases expression	2
Estradiol	affects expression, affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Aflatoxin B1	affects methylation, decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
GSK-J4	decreases expression	1
afuresertib	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	increases expression	1
tremortin	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
trichostatin A	decreases expression	1
beta-lapachone	decreases expression	1
o,p’-DDT	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1050579	Binding	Binding affinity to delta-6 saturase in human HepG2 cells by whole cell assay	Thiazole analog as stearoyl-CoA desaturase 1 inhibitor. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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