FASN

Summary

FASN (fatty acid synthase, HGNC:3594) is a protein-coding gene on chromosome 17q25.3, encoding Fatty acid synthase (P49327). Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. It is a selective cancer dependency (DepMap: 21.1% of cell lines).

The enzyme encoded by this gene is a multifunctional protein. Its main function is to catalyze the synthesis of palmitate from acetyl-CoA and malonyl-CoA, in the presence of NADPH, into long-chain saturated fatty acids. In some cancer cell lines, this protein has been found to be fused with estrogen receptor-alpha (ER-alpha), in which the N-terminus of FAS is fused in-frame with the C-terminus of ER-alpha.

Source: NCBI Gene 2194 — RefSeq curated summary.

At a glance

• Gene–disease (curated): FAS-related autoimmune lymphoproliferative immune disorder (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 25
• Clinical variants (ClinVar): 3,016 total — 74 pathogenic, 37 likely-pathogenic
• Phenotypes (HPO): 187
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 21.1% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004104

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3594
Approved symbol	FASN
Name	fatty acid synthase
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	FAS, SDR27X1
Ensembl gene	ENSG00000169710
Ensembl biotype	protein_coding
OMIM	600212
Entrez	2194

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 12 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000306749, ENST00000578424, ENST00000579410, ENST00000580382, ENST00000584610, ENST00000634990, ENST00000635197, ENST00000635733, ENST00000636628, ENST00000636968, ENST00000637026, ENST00000637525, ENST00000637693, ENST00000940341, ENST00000940342, ENST00000940343, ENST00000940344, ENST00000940345, ENST00000940346

RefSeq mRNA: 1 — MANE Select: NM_004104 NM_004104

CCDS: CCDS11801

Canonical transcript exons

ENST00000306749 — 43 exons

Exon	Start	End
ENSE00001163260	82082009	82082160
ENSE00001163279	82083202	82083425
ENSE00001163286	82083517	82083639
ENSE00001163293	82083772	82083891
ENSE00001163299	82083975	82084153
ENSE00001163306	82084234	82084384
ENSE00001163312	82084513	82084716
ENSE00001163317	82084799	82084953
ENSE00001163322	82085035	82085156
ENSE00001163328	82085238	82085402
ENSE00001163334	82085482	82085871
ENSE00001163338	82086254	82086558
ENSE00001163343	82087050	82087253
ENSE00001379760	82098121	82098236
ENSE00002430713	82087685	82087861
ENSE00002430931	82093598	82093771
ENSE00002445152	82092697	82092812
ENSE00002445306	82090375	82090564
ENSE00002447069	82092897	82093019
ENSE00002462052	82088969	82089172
ENSE00002462687	82087325	82087504
ENSE00002465117	82089250	82089384
ENSE00002473356	82090882	82091069
ENSE00002476146	82088116	82088307
ENSE00002487461	82095320	82095472
ENSE00002491931	82088761	82088876
ENSE00002492700	82092455	82092589
ENSE00002502969	82087954	82088034
ENSE00002514446	82091222	82091684
ENSE00002515186	82093219	82093419
ENSE00002525767	82089632	82089726
ENSE00002529317	82088390	82088562
ENSE00002529623	82081164	82081352
ENSE00002531041	82081601	82081843
ENSE00002722063	82078338	82079280
ENSE00002726439	82096319	82096452
ENSE00003491795	82079357	82079608
ENSE00003526112	82082527	82082678
ENSE00003570680	82080370	82080590
ENSE00003607244	82080692	82080922
ENSE00003625386	82082323	82082414
ENSE00003633938	82082914	82083115
ENSE00003684368	82080140	82080238

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 98.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 154.6220 / max 3429.4589, expressed in 1821 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168919	151.6832	1816
208465	2.8038	1214
168906	0.1350	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.79	gold quality
endometrium epithelium	UBERON:0004811	98.49	gold quality
skin of abdomen	UBERON:0001416	98.47	gold quality
cerebellar hemisphere	UBERON:0002245	98.43	gold quality
cerebellar cortex	UBERON:0002129	98.38	gold quality
skin of leg	UBERON:0001511	98.35	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.27	gold quality
omental fat pad	UBERON:0010414	98.26	gold quality
cortical plate	UBERON:0005343	98.25	gold quality
adenohypophysis	UBERON:0002196	98.19	gold quality
peritoneum	UBERON:0002358	98.18	gold quality
right lobe of liver	UBERON:0001114	97.96	gold quality
adipose tissue	UBERON:0001013	97.85	gold quality
nipple	UBERON:0002030	97.67	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.64	gold quality
cerebellum	UBERON:0002037	97.59	gold quality
right frontal lobe	UBERON:0002810	97.57	gold quality
lower esophagus mucosa	UBERON:0035834	97.43	gold quality
pituitary gland	UBERON:0000007	97.29	gold quality
right lung	UBERON:0002167	97.28	gold quality
body of stomach	UBERON:0001161	97.08	gold quality
ventricular zone	UBERON:0003053	97.00	gold quality
right adrenal gland cortex	UBERON:0035827	96.90	gold quality
upper lobe of left lung	UBERON:0008952	96.63	gold quality
upper lobe of lung	UBERON:0008948	96.60	gold quality
nerve	UBERON:0001021	96.57	gold quality
tibial nerve	UBERON:0001323	96.57	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.57	gold quality
minor salivary gland	UBERON:0001830	96.55	gold quality
prefrontal cortex	UBERON:0000451	96.53	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	4619.53
E-MTAB-10855	yes	4457.06
E-MTAB-3929	yes	349.12
E-MTAB-8495	yes	171.35
E-GEOD-76312	yes	72.05
E-ANND-3	yes	24.91
E-ENAD-17	no	28.19
E-CURD-112	no	2.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, CCDC3, CEBPA, CNBP, CREBZF, EGR1, ESR1, FOS, FOXO1, HIF1A, HNF4A, ID1, JUN, KLF5, MLXIPL, MYC, NR1H3, NR1H4, NR5A2, PC, PKNOX1, PPARD, RORA, SP1, SP3, SREBF1, SREBF2, STAT3, STAT5A, TP53, TP63, TP73, USF1, USF2, WT1, XBP1, ZBTB7A, ZBTB7C

miRNA regulators (miRDB)

47 targeting FASN, 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-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-122B-3P	99.21	68.90	1333
HSA-MIR-21-3P	99.21	68.95	1312
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-4651	99.06	67.57	2002

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 21.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• We present the first three-dimensional reconstruction of human fatty acid synthase obtained by electron cryomicroscopy and single-particle image processing (PMID:11756679)
• regulation of expression by liver X receptors (PMID:11790787)
• Domain movements in human fatty acid synthase by quantized elastic deformational model (PMID:12060737)
• expression of FAS is affected by polyunsaturated fatty acids in human cells (PMID:12213084)
• Fatty acid synthase in the specimens of non-small cell lung cancer patients has no correlation with most clinical factors, except that, in early lesions, it may signify poor prognosis. (PMID:12515624)
• Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c. (PMID:12531699)
• Data point to a link between fatty acid synthase overexpression and dysregulation of membrane composition and functioning in tumor cells. (PMID:12646257)
• RNA interference-mediated silencing of this gene attenuates growth and induces morphological changes and apoptosis of prostate cancer cells. (PMID:12839976)
• compelling evidence that human mitochondria contain a malonyl-CoA/acyl carrier protein-dependent fatty acid synthase system (PMID:12882974)
• a strong association between FAS expression and prostate tumor initiation and progression (PMID:12939396)
• FAS plays in important cellular processes such as apoptosis and proliferation. Because of the frequent overexpression of this enzyme prostate cancer, FAS constitutes a therapeutic target in this disease [review]. (PMID:14689581)
• cellular FAS activity is important for induction of immediate-early gene BZLF1 transcription from the intact latent EBV genome (PMID:15047835)
• Regions responsible for hormonal regulation of the FAS gene lie in the proximal portion of the gene’s 5’-flanking region, within which we identified an insulin response element. (PMID:15113941)
• Val1483Ile substitution in FAS is protective against obesity in Pima Indians, an effect possibly explained by the role of this gene in the regulation of substrate oxidation. (PMID:15220220)
• Data suggest that HER2 may act as the key molecular sensor of energy imbalance after the perturbation of tumor-associated fatty acid synthase hyperactivity in cancer cells. (PMID:15235125)
• breast cancer-associated FAS plays an active role in human breast cancer chemosensitivity (PMID:15254710)
• 2.6-A resolution structure (PMID:15507492)
• study reveals for the first time that extracellular acidosis can work in an epigenetic fashion by up-regulating the transcriptional expression of FAS gene (PMID:15523670)
• Repression of FAS mRNA expression is the consequence of feedback inhibition of FAS expression by long chain fatty acyl-CoAs, which are formed by FACL3 during its upregulation by vitamin D3 in prostate cancer cells. (PMID:15556626)
• FAS blockade should result in a concomitant down-regulation of VEGF (PMID:15669079)
• Our results indicate that the specific inhibition of fatty acid synthase (FAS) gene by siRNA leads to apoptosis of prostate tumor cells, and inhibition of PI 3-kinase pathway synergizes with FAS siRNA to enhance tumor cell death. (PMID:15897909)
• increased expression in 7 of 8 patients with invasive Paget’s disease of the vulva (PDV), 3 of 4 patients with microinvasive PDV & 1 of 8 patients with noninvasive PDV; statistical analysis revealed increased expression was associated with invasive PDV (PMID:16175090)
• analysis of human fatty-acid synthase substrate recognition (PMID:16215233)
• Fatty acid synthase (FAS) gene, encoding for a key enzyme involved in the biogenesis of membrane lipids in rapidly proliferating cells, is a conserved target of the p53 family throughout the evolution. (PMID:16582625)
• Tamoxifen can modulate appetite through alterations in FAS expression and malonyl-CoA levels suggesting a link between hypothalamic sex steroid receptors, fatty acid metabolism, and feeding behavior. (PMID:16644689)
• thiazolidinediones upregulate the adipocyte lipid storage genes DGAT and FAS but have no significant effect on LPL (PMID:16894240)
• HCV-3a core protein has a stronger effect on fatty acid synthase activation in comparison to HCV-1b core, which could contribute to the higher prevalence and severity of steatosis in HCV-3a infections (PMID:17188392)
• FAS protein was expressed in all the three breast cancer cell lines with different levels, but its expression in NIH3T3 was not detected. FAS protein was localized primarily in cytosol. (PMID:17488603)
• FASN gene expression in adipose tissue is linked to visceral fat accumulation, impaired insulin sensitivity, increased circulating fasting insulin, IL-6, leptin and RBP4 (PMID:17492427)
• reduced expression of the fatty acid synthase gene in adipose tissues of obese subjects. (PMID:17618104)
• The crystal structure of the thioesterase domain of FAS is determined. (PMID:17618296)
• the major mechanism of HER2-mediated induction of FASN and ACCalpha in the breast cancer cells used in this study is translational regulation primarily through the mTOR signaling pathway. (PMID:17631500)
• By using cerulenin and C75, two known inhibitors of FAS we were able to significantly block CVB3 replication. (PMID:17662476)
• Fatty acid synthase [FAS] activity levels were higher in cancer than in the corresponding normal mucosa. Tumors on the left side of the colon showed higher FAS activity; tumors from male patients showed higher activity than tumors from females. (PMID:17687193)
• Surface analysis identified the ligand-binding pocket of the thioesterase domain that encompasses the catalytic triad of Ser2308, His2481, Asp2338. Docking of palmitate into this pocket revealed the ligand-binding mode (PMID:17847090)
• cannot definitely establish FASN as a novel oncogene in breast cancer, but this study reveals that exacerbated endogenous FA biosynthesis in non-cancerous epithelial cells is sufficient to induce a cancer-like phenotype dependent on HER1/HER2 duo (PMID:18211286)
• Dietary soy protein, by decreasing circulating insulin levels and colon FASN expression, attenuates insulin-induced DNA damage and FASN-mediated anti-apoptosis during carcinogenesis. (PMID:18239060)
• FAS gene is up-regulated by hypoxia via activation of the Akt and HIF1 followed by the induction of the SREBP-1 gene, and that hypoxia-induced chemoresistance is partly due to the up-regulation of FAS. (PMID:18281474)
• FASN overexpression is a new mechanism of drug resistance and may be an ideal target for chemosensitization in breast cancer chemotherapy. (PMID:18281512)
• expression in squamous cell carcinoma of the tongue is associated with microscopic characteristics that determine disease progression and prognosis (PMID:18410580)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fasn	ENSDARG00000087657
mus_musculus	Fasn	ENSMUSG00000025153
rattus_norvegicus	Fasn	ENSRNOG00000045636
drosophila_melanogaster	FASN2	FBGN0042627
drosophila_melanogaster	FASN1	FBGN0283427
caenorhabditis_elegans	F32H2.6	WBGENE00009343

Paralogs (1): OXSM (ENSG00000151093)

Protein

Protein identifiers

Fatty acid synthase — P49327 (reviewed: P49327)

Alternative names: Type I fatty acid synthase

All UniProt accessions (7): A0A0U1RQF0, A0A0U1RRG3, A0A1B0GTR5, A0A1B0GVK4, A0A1B0GWG8, P49327, J3KTF0

UniProt curated annotations — full annotation on UniProt →

Function. Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4’-phosphopantetheine of the acyl carrier protein ([ACP]) domain. (Microbial infection) Fatty acid synthetase activity is required for SARS coronavirus-2/SARS-CoV-2 replication.

Subunit / interactions. Homodimer which is arranged in a head to tail fashion (PubMed:17618296, PubMed:18022563, Ref.34). Interacts with CEACAM1; this interaction is insulin and phosphorylation-dependent; reduces fatty-acid synthase activity.

Subcellular location. Cytoplasm. Melanosome.

Tissue specificity. Ubiquitous. Prominent expression in brain, lung, liver and mammary gland.

Post-translational modifications. S-nitrosylation of Fatty acid synthase at cysteine residues Cys-1471 or Cys-2091 is important for the enzyme dimerization. In adipocytes, S-nitrosylation of Fatty acid synthase occurs under physiological conditions and gradually increases during adipogenesis.

Activity regulation. Activated by S-nitrosylation which promotes enzyme dimerization. Cerulenin, a potent non-competitive pharmacological inhibitor of FAS, binds covalently to the active site of the condensing enzyme region, inactivating a key enzyme step in fatty acid synthesis.

Pathway. Lipid metabolism; fatty acid biosynthesis.

Miscellaneous. The relatively low beta-ketoacyl synthase activity may be attributable to the low 4’-phosphopantetheine content of the protein.

RefSeq proteins (1): NP_004095* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001031	Thioesterase	Domain
IPR001227	Ac_transferase_dom_sf	Homologous_superfamily
IPR006162	Ppantetheine_attach_site	PTM
IPR009081	PP-bd_ACP	Domain
IPR011032	GroES-like_sf	Homologous_superfamily
IPR013149	ADH-like_C	Domain
IPR013217	Methyltransf_12	Domain
IPR013968	PKS_KR	Domain
IPR014030	KAS_N	Domain
IPR014031	KAS_C	Domain
IPR014043	Acyl_transferase_dom	Domain
IPR016035	Acyl_Trfase/lysoPLipase	Homologous_superfamily
IPR016036	Malonyl_transacylase_ACP-bd	Homologous_superfamily
IPR016039	Thiolase-like	Homologous_superfamily
IPR018201	Ketoacyl_synth_AS	Active_site
IPR020806	PKS_PP-bd	Domain
IPR020807	PKS_DH	Domain
IPR020841	PKS_Beta-ketoAc_synthase_dom	Domain
IPR020843	ER	Domain
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR032821	PKS_assoc	Domain
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR036736	ACP-like_sf	Homologous_superfamily
IPR042104	PKS_dehydratase_sf	Homologous_superfamily
IPR049391	FAS_pseudo-KR	Domain
IPR049552	PKS_DH_N	Domain
IPR049900	PKS_mFAS_DH	Domain
IPR050091	PKS_NRPS_Biosynth_Enz	Family
IPR057326	KR_dom	Domain

Pfam: PF00107, PF00109, PF00550, PF00698, PF00975, PF02801, PF08242, PF08659, PF16197, PF21089, PF21149

Enzyme classification (BRENDA):

• EC 2.3.1.39 — [acyl-carrier-protein] S-malonyltransferase (BRENDA: 37 organisms, 73 substrates, 50 inhibitors, 77 Km, 35 kcat entries)
• EC 2.3.1.85 — fatty-acid synthase system (BRENDA: 19 organisms, 29 substrates, 130 inhibitors, 45 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
MALONYL-COA	0.0013–1.4	43
MALONYL-COA	0.001–0.1	12
NADPH	0.0041–2.7	11
[ACYL-CARRIER PROTEIN]	0.075–3.5	10
ACETYL-COA	0.0005–0.008	10
ACYL-CARRIER PROTEIN	0.042–1.3	7
AN [ACYL-CARRIER PROTEIN]	0.011–0.04	6
METHYLMALONYL-COA	0.016–0.58	4
MALONYL COA	0.0094–0.015	2
ACETOACETYL-COA	0.11	1
ACETYL-COA	0.2	1
HOLO-ACYL-CARRIER PROTEIN	0.0141	1
PANTETHEINE	0.0013	1
3-HYDROXYBUTANOYL-COA	0.0017	1
3-METHYLBUTANOYL-COA	0.0021	1

Catalyzed reactions (Rhea), 12 shown:

• a (3R)-hydroxyacyl-[ACP] = a (2E)-enoyl-[ACP] + H2O (RHEA:13097)
• a (3R)-hydroxyacyl-[ACP] + NADP(+) = a 3-oxoacyl-[ACP] + NADPH + H(+) (RHEA:17397)
• a 2,3-saturated acyl-[ACP] + NADP(+) = a (2E)-enoyl-[ACP] + NADPH + H(+) (RHEA:22564)
• a fatty acyl-[ACP] + malonyl-[ACP] + H(+) = a 3-oxoacyl-[ACP] + holo-[ACP] + CO2 (RHEA:22836)
• tetradecanoyl-[ACP] + H2O = tetradecanoate + holo-[ACP] + H(+) (RHEA:30123)
• holo-[ACP] + acetyl-CoA = acetyl-[ACP] + CoA (RHEA:41788)
• holo-[ACP] + malonyl-CoA = malonyl-[ACP] + CoA (RHEA:41792)
• acetyl-[ACP] + malonyl-[ACP] + H(+) = 3-oxobutanoyl-[ACP] + holo-[ACP] + CO2 (RHEA:41800)
• 3-oxobutanoyl-[ACP] + NADPH + H(+) = (3R)-hydroxybutanoyl-[ACP] + NADP(+) (RHEA:41804)
• (3R)-hydroxybutanoyl-[ACP] = (2E)-butenoyl-[ACP] + H2O (RHEA:41808)
• (2E)-butenoyl-[ACP] + NADPH + H(+) = butanoyl-[ACP] + NADP(+) (RHEA:41812)
• butanoyl-[ACP] + malonyl-[ACP] + H(+) = 3-oxohexanoyl-[ACP] + holo-[ACP] + CO2 (RHEA:41820)

UniProt features (341 total): strand 125, helix 112, turn 29, modified residue 28, sequence conflict 19, active site 8, region of interest 6, binding site 5, sequence variant 4, domain 3, chain 1, cross-link 1

Structure

Experimental structures (PDB)

34 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
3TJM	X-RAY DIFFRACTION	1.48
4W82	X-RAY DIFFRACTION	1.7
4Z49	X-RAY DIFFRACTION	1.7
8ZEV	X-RAY DIFFRACTION	1.8
8G7X	X-RAY DIFFRACTION	1.81
4W9N	X-RAY DIFFRACTION	1.84
9MJ9	ELECTRON MICROSCOPY	2
7MHD	X-RAY DIFFRACTION	2.03
3HHD	X-RAY DIFFRACTION	2.15
6NNA	X-RAY DIFFRACTION	2.26
4PIV	X-RAY DIFFRACTION	2.3
2PX6	X-RAY DIFFRACTION	2.3
5C37	X-RAY DIFFRACTION	2.3
2JFK	X-RAY DIFFRACTION	2.4
8GKC	ELECTRON MICROSCOPY	2.45
9B7Z	ELECTRON MICROSCOPY	2.5
1XKT	X-RAY DIFFRACTION	2.6
2CG5	X-RAY DIFFRACTION	2.7
8EYI	ELECTRON MICROSCOPY	2.7
8EYK	ELECTRON MICROSCOPY	2.7
9B80	ELECTRON MICROSCOPY	2.7
7MHE	X-RAY DIFFRACTION	2.8
2JFD	X-RAY DIFFRACTION	2.81
8VG4	ELECTRON MICROSCOPY	3.11
8VF7	ELECTRON MICROSCOPY	3.2
8VLP	ELECTRON MICROSCOPY	3.2
8VLE	ELECTRON MICROSCOPY	3.3
8VLO	ELECTRON MICROSCOPY	3.3
8VM0	ELECTRON MICROSCOPY	3.3
8VM5	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49327-F1	85.65	0.48

Functional residue map

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

Catalytic / active sites (8): 161 (for beta-ketoacyl synthase activity); 293 (for beta-ketoacyl synthase activity); 331 (for beta-ketoacyl synthase activity); 581 (for malonyltransferase activity); 878 (proton acceptor; for dehydratase activity); 1031 (proton donor; for dehydratase activity); 2308 (for thioesterase activity); 2481 (for thioesterase activity)

Ligand- & substrate-binding residues (5): 647–648; 671; 773; 1671–1688; 1886–1901

Post-translational modifications (29): 1, 63, 70, 207, 298, 436, 528, 673, 725, 992, 1174, 1411, 1471, 1584, 1594, 1704, 1704, 1771, 1847, 1995 …

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-163765	ChREBP activates metabolic gene expression
R-HSA-199220	Vitamin B5 (pantothenate) metabolism
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-75105	Fatty acyl-CoA biosynthesis
R-HSA-9029558	NR1H2 & NR1H3 regulate gene expression linked to lipogenesis
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9918487	Dengue Virus Genome Translation and Replication

MSigDB gene sets: 1230 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, MODULE_93, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_EPITHELIUM_DEVELOPMENT, HORIUCHI_WTAP_TARGETS_DN, JI_RESPONSE_TO_FSH_UP, FARMER_BREAST_CANCER_CLUSTER_7, GOBP_REGULATION_OF_STRESS_ACTIVATED_PROTEIN_KINASE_SIGNALING_CASCADE, GOBP_RESPONSE_TO_INTERLEUKIN_4, GOBP_RESPONSE_TO_PEPTIDE, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_ESTABLISHMENT_OF_ENDOTHELIAL_INTESTINAL_BARRIER, GOBP_CELLULAR_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (21): osteoblast differentiation (GO:0001649), acetyl-CoA metabolic process (GO:0006084), fatty acid metabolic process (GO:0006631), fatty acid biosynthetic process (GO:0006633), inflammatory response (GO:0006954), response to nutrient (GO:0007584), ether lipid biosynthetic process (GO:0008611), neutrophil differentiation (GO:0030223), monocyte differentiation (GO:0030224), mammary gland development (GO:0030879), host-mediated perturbation of viral process (GO:0044788), fatty-acyl-CoA biosynthetic process (GO:0046949), response to caloric restriction (GO:0061771), cellular response to interleukin-4 (GO:0071353), establishment of endothelial intestinal barrier (GO:0090557), epithelial cell development (GO:0002064), lipid metabolic process (GO:0006629), lipid biosynthetic process (GO:0008610), biosynthetic process (GO:0009058), tissue development (GO:0009888), response to nutrient levels (GO:0031667)

GO Molecular Function (19): RNA binding (GO:0003723), fatty acid synthase activity (GO:0004312), [acyl-carrier-protein] S-acetyltransferase activity (GO:0004313), [acyl-carrier-protein] S-malonyltransferase activity (GO:0004314), 3-oxoacyl-[acyl-carrier-protein] synthase activity (GO:0004315), 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity (GO:0004316), fatty acyl-[ACP] hydrolase activity (GO:0016297), (3R)-hydroxyacyl-[acyl-carrier-protein] dehydratase activity (GO:0019171), phosphopantetheine binding (GO:0031177), identical protein binding (GO:0042802), cadherin binding (GO:0045296), enoyl-[acyl-carrier-protein] reductase (NADPH) activity (GO:0141148), catalytic activity (GO:0003824), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), hydrolase activity (GO:0016787), lyase activity (GO:0016829)

GO Cellular Component (8): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), melanosome (GO:0042470), glycogen granule (GO:0042587), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Dengue Virus Infection	2
Integration of energy metabolism	1
Metabolism of water-soluble vitamins and cofactors	1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Fatty acid metabolism	1
NR1H2 and NR1H3-mediated signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	4
cellular anatomical structure	4
cytoplasm	3
lipid metabolic process	2
lipid biosynthetic process	2
response to nutrient levels	2
acyltransferase activity, transferring groups other than amino-acyl groups	2
ossification	1
cell differentiation	1
acyl-CoA metabolic process	1
monocarboxylic acid metabolic process	1
fatty acid metabolic process	1
monocarboxylic acid biosynthetic process	1
defense response	1
response to chemical	1
ether lipid metabolic process	1
glycerol ether biosynthetic process	1
granulocyte differentiation	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
gland development	1
host-mediated perturbation of symbiont process	1
fatty-acyl-CoA metabolic process	1
acyl-CoA biosynthetic process	1
fatty acid derivative biosynthetic process	1
response to stress	1
response to interleukin-4	1
cellular response to cytokine stimulus	1
establishment of endothelial barrier	1
epithelial cell differentiation	1
cell development	1
primary metabolic process	1
biosynthetic process	1
metabolic process	1
anatomical structure development	1
nucleic acid binding	1
S-acetyltransferase activity	1
S-malonyltransferase activity	1
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	1
thiolester hydrolase activity	1

Protein interactions and networks

STRING

5026 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FASN	ACACA	Q13085	965
FASN	SREBF1	P36956	957
FASN	ACACB	O00763	909
FASN	ACLY	P53396	895
FASN	SCD	O00767	890
FASN	ELOVL6	Q9H5J4	881
FASN	PPARG	P37231	860
FASN	DGAT2	Q96PD7	829
FASN	CPT1A	P50416	810
FASN	HMGCR	P04035	807
FASN	SREBF2	Q12772	794
FASN	ACSL1	P33121	791
FASN	PPARA	Q07869	784
FASN	ESR1	P03372	780
FASN	HMGCS1	Q01581	769

IntAct

281 interactions, top by confidence:

A	B	Type	Score
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
HTT	FASN	psi-mi:“MI:0915”(physical association)	0.670
CDS1	CDS2	psi-mi:“MI:0914”(association)	0.670
FASN	LNX1	psi-mi:“MI:0915”(physical association)	0.560
FASN	ADIPOQ	psi-mi:“MI:0915”(physical association)	0.560
FASN		psi-mi:“MI:0915”(physical association)	0.560
LACC1	FASN	psi-mi:“MI:0915”(physical association)	0.540

BioGRID (1244): FASN (Affinity Capture-MS), FASN (Affinity Capture-MS), FASN (Affinity Capture-MS), FASN (Affinity Capture-MS), FASN (Affinity Capture-MS), FASN (Affinity Capture-MS), USP2 (Affinity Capture-Western), FASN (Affinity Capture-Western), FASN (Affinity Capture-MS), PTGR2 (Affinity Capture-MS), KIF3A (Affinity Capture-MS), IMPDH1 (Affinity Capture-MS), HAUS4 (Affinity Capture-MS), FASN (Two-hybrid), FASN (Affinity Capture-MS)

ESM2 similar proteins: A1L134, A5A779, A6QLU7, E1BNQ4, E2QUI9, O00519, O08914, O60294, P12785, P17256, P49327, P79106, P83006, P97612, Q05AM4, Q08602, Q0VGK3, Q5EA80, Q5NVK5, Q5R7A2, Q5R824, Q5XIA3, Q64FG0, Q6DH69, Q6GMR7, Q6NUM9, Q6QHF9, Q6UX53, Q71SP7, Q7TMC8, Q865R1, Q86TX2, Q8BQJ6, Q8BYL4, Q8BYR1, Q8C0L6, Q8CHW4, Q8IW45, Q8N0W3, Q8NF37

Diamond homologs: A0A0C1BUW8, A0A0C1E3B7, A0A0S1RUN4, A0A0S2E7V8, A0A0S2E7W3, A0A0S2E7W7, A0A0S2E7X0, A0A0S2E7Z1, A0A179HJB8, A0A336U965, A0A6F9DYX9, A7XRY0, B2HGV4, B3FWS8, B7STY1, C5D6U5, F8P1W3, I3PB36, I6NXV7, M4IRL4, M4IS88, M4IS92, O31826, P12276, P27743, P39518, P44446, P49327, P9WES4, Q0CBN5, Q0CRX1, Q0CT94, Q0CU19, Q0CWD0, Q0D034, Q0DV32, Q0K844, Q1MWN4, Q5B7T4, Q5FVE4

SIGNOR signaling

24 interactions.

A	Effect	B	Mechanism
SREBF1	“up-regulates quantity by expression”	FASN	“transcriptional regulation”
FASN	up-regulates	Lipogenesis
FASN	“up-regulates quantity by stabilization”	CTNNB1
FASN	“up-regulates activity”	WNT1
FASN	“up-regulates quantity”	“long-chain fatty acid anion”	“chemical modification”
FASN	“down-regulates quantity”	acetyl-CoA	“chemical modification”
FASN	“down-regulates quantity”	malonyl-CoA	“chemical modification”
KAT8	“down-regulates quantity by destabilization”	FASN	acetylation
HDAC3	“up-regulates quantity by stabilization”	FASN	deacetylation
TRIM21	“down-regulates quantity by destabilization”	FASN	ubiquitination
NADPH(4-)	“up-regulates activity”	FASN	binding
FASN	“up-regulates quantity”	“hexadecanoic acid”	“chemical modification”
FASN	“down-regulates quantity”	NADPH(4-)	“chemical modification”
HACD1	“up-regulates activity”	FASN	“chemical activation”
HACD2	“up-regulates activity”	FASN	“chemical activation”
HACD3	“up-regulates activity”	FASN	“chemical activation”
HACD4	“up-regulates activity”	FASN	“chemical activation”
HACD	“up-regulates activity”	FASN	“chemical activation”
FASN	“up-regulates quantity”	“coenzyme A(4-)”	“chemical modification”
FASN	“up-regulates quantity”	NADP(3-)	“chemical modification”
FASN	up-regulates	Fatty_Acid_Biosynthesis
ERBB2	“up-regulates activity”	FASN	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 192 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
Signaling by high-kinase activity BRAF mutants	6	13.8×	1e-03
RHO GTPases activate IQGAPs	5	12.5×	3e-03
MAP2K and MAPK activation	6	12.4×	1e-03
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	8	11.2×	3e-04
Signaling by moderate kinase activity BRAF mutants	6	11.0×	1e-03
Paradoxical activation of RAF signaling by kinase inactive BRAF	6	11.0×	1e-03
Signaling downstream of RAS mutants	6	11.0×	1e-03
Aggrephagy	6	10.8×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrion organization	9	8.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

3016 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	74
Likely pathogenic	37
Uncertain significance	1409
Likely benign	1230
Benign	137

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1067934	NM_000043.6(FAS):c.778G>A (p.Asp260Asn)	Pathogenic
1070181	NM_000043.6(FAS):c.676+1G>T	Pathogenic
1070958	NM_000043.6(FAS):c.442A>T (p.Lys148Ter)	Pathogenic
1071139	NM_000043.6(FAS):c.644T>A (p.Leu215Ter)	Pathogenic
1074734	NM_000043.6(FAS):c.657del (p.Val220fs)	Pathogenic
1357498	NM_000043.6(FAS):c.816del (p.Glu272fs)	Pathogenic
1373595	NM_000043.6(FAS):c.707_708insG (p.Ile236fs)	Pathogenic
1413808	NM_000043.6(FAS):c.182_183insTTAT (p.Lys61fs)	Pathogenic
1443489	NM_000043.6(FAS):c.312dup (p.Arg105Ter)	Pathogenic
1451181	NM_000043.6(FAS):c.259G>T (p.Glu87Ter)	Pathogenic
1455090	NM_000043.6(FAS):c.403del (p.Cys135fs)	Pathogenic
1457614	NM_000043.6(FAS):c.528G>A (p.Trp176Ter)	Pathogenic
1506283	NM_000043.6(FAS):c.506-16A>G	Pathogenic
16497	NM_000043.6(FAS):c.232del (p.Asp78fs)	Pathogenic
16498	NM_000043.6(FAS):c.334+2dup	Pathogenic
16499	NM_000043.6(FAS):c.721A>C (p.Thr241Pro)	Pathogenic
16500	NM_000043.6(FAS):c.569-2A>C	Pathogenic
16501	NM_000043.6(FAS):c.817C>T (p.Gln273Ter)	Pathogenic
16504	NM_000043.6(FAS):c.779A>T (p.Asp260Val)	Pathogenic
16505	NM_000043.6(FAS):c.749G>C (p.Arg250Pro)	Pathogenic
16507	NM_000043.6(FAS):c.651+2T>A	Pathogenic
16508	NM_000043.6(FAS):c.73G>A (p.Ala25Thr)	Pathogenic
16509	NM_000043.6(FAS):c.968_987dup (p.Glu330fs)	Pathogenic
16510	NM_000043.6(FAS):c.763A>G (p.Asn255Asp)	Pathogenic
16511	NM_000043.6(FAS):c.353A>G (p.Asn118Ser)	Pathogenic
16512	NM_000043.6(FAS):c.532T>C (p.Cys178Arg)	Pathogenic
16513	NM_000043.6(FAS):c.740G>C (p.Gly247Ala)	Pathogenic
16514	NM_000043.6(FAS):c.651+2T>C	Pathogenic
16515	NM_000043.6(FAS):c.692_693insT (p.Lys231fs)	Pathogenic
16516	NM_000043.6(FAS):c.778G>T (p.Asp260Tyr)	Pathogenic

SpliceAI

6741 predictions. Top by Δscore:

Variant	Effect	Δscore
17:82079278:TACCT:T	acceptor_loss	1.0000
17:82079280:CCT:C	acceptor_loss	1.0000
17:82079281:C:CA	acceptor_loss	1.0000
17:82079352:CGCA:C	donor_loss	1.0000
17:82079353:GCAC:G	donor_loss	1.0000
17:82079354:CA:C	donor_loss	1.0000
17:82079355:A:AC	donor_gain	1.0000
17:82079355:A:C	donor_loss	1.0000
17:82079356:C:CC	donor_gain	1.0000
17:82079606:CACCT:C	acceptor_loss	1.0000
17:82079608:CCTG:C	acceptor_loss	1.0000
17:82079609:C:CA	acceptor_loss	1.0000
17:82080138:AC:A	donor_gain	1.0000
17:82080139:CC:C	donor_gain	1.0000
17:82080364:TCTCA:T	donor_loss	1.0000
17:82080365:CTCA:C	donor_loss	1.0000
17:82080366:TCA:T	donor_loss	1.0000
17:82080367:CACCT:C	donor_loss	1.0000
17:82080368:A:T	donor_loss	1.0000
17:82080369:C:CA	donor_loss	1.0000
17:82080918:CAGCT:C	acceptor_gain	1.0000
17:82080919:AGCT:A	acceptor_gain	1.0000
17:82080922:TC:T	acceptor_loss	1.0000
17:82080923:C:CC	acceptor_gain	1.0000
17:82081160:GCACC:G	donor_loss	1.0000
17:82081161:CA:C	donor_loss	1.0000
17:82081162:A:AC	donor_gain	1.0000
17:82081162:A:C	donor_loss	1.0000
17:82081163:C:CA	donor_loss	1.0000
17:82081163:C:CC	donor_gain	1.0000

AlphaMissense

16223 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:82083590:G:C	S1756R	0.999
17:82083590:G:T	S1756R	0.999
17:82083592:T:G	S1756R	0.999
17:82083620:G:C	N1746K	0.999
17:82083620:G:T	N1746K	0.999
17:82083561:A:G	F1766S	0.998
17:82090504:A:G	S581P	0.998
17:82093382:G:C	S164R	0.998
17:82093382:G:T	S164R	0.998
17:82093384:T:G	S164R	0.998
17:82083627:A:T	V1744D	0.997
17:82083806:G:C	F1728L	0.997
17:82083806:G:T	F1728L	0.997
17:82083808:A:G	F1728L	0.997
17:82089131:G:C	S714R	0.997
17:82089131:G:T	S714R	0.997
17:82089133:T:G	S714R	0.997
17:82089139:A:G	W712R	0.997
17:82089139:A:T	W712R	0.997
17:82089665:G:C	N644K	0.997
17:82089665:G:T	N644K	0.997
17:82096328:A:G	W40R	0.997
17:82096328:A:T	W40R	0.997
17:82083560:G:C	F1766L	0.996
17:82083560:G:T	F1766L	0.996
17:82083562:A:G	F1766L	0.996
17:82083579:A:C	L1760W	0.996
17:82083624:A:G	L1745S	0.996
17:82084565:G:C	N1572K	0.996
17:82084565:G:T	N1572K	0.996

dbSNP variants (sampled 300 via entrez): RS1000057160 (17:82081529 C>A,T), RS1000499781 (17:82086297 G>A), RS1000503457 (17:82086512 C>T), RS1000691046 (17:82082795 T>C), RS1000783032 (17:82098612 G>A,T), RS1000919802 (17:82097755 C>T), RS1000960709 (17:82090231 C>T), RS1001371193 (17:82098166 G>A), RS1001378134 (17:82098109 G>A,C), RS1001425157 (17:82099033 C>T), RS1001510211 (17:82083960 G>C), RS1001587249 (17:82097059 G>A), RS1001987486 (17:82078701 C>G,T), RS1002352184 (17:82086639 C>A,T), RS1002460348 (17:82094122 C>A)

Disease associations

OMIM: gene MIM:600212 | disease phenotypes: MIM:601859, MIM:611788

GenCC curated gene-disease

Disease	Classification	Inheritance
autoimmune lymphoproliferative syndrome type 1	Definitive	Autosomal dominant
autoimmune lymphoproliferative syndrome	Definitive	Autosomal dominant
neurodevelopmental disorder	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
FAS-related autoimmune lymphoproliferative immune disorder	Definitive	SD

Mondo (10): autoimmune lymphoproliferative syndrome type 1 (MONDO:0011158), aortic aneurysm, familial thoracic 6 (MONDO:0012730), thrombocytopenia (MONDO:0002049), esotropia (MONDO:0004896), hearing loss disorder (MONDO:0005365), familial isolated clinodactyly of fingers (MONDO:0017461), autoimmune lymphoproliferative syndrome (MONDO:0017979), hepatoblastoma (MONDO:0018666), autism spectrum disorder (MONDO:0005258), neurodevelopmental disorder (MONDO:0700092)

Orphanet (4): Autoimmune lymphoproliferative syndrome (Orphanet:3261), Familial isolated clinodactyly of fingers (Orphanet:295014), Hepatoblastoma (Orphanet:449), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

187 total (30 of 187 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000031	Epididymitis
HP:0000083	Renal insufficiency
HP:0000099	Glomerulonephritis
HP:0000155	Oral ulcer
HP:0000360	Tinnitus
HP:0000407	Sensorineural hearing impairment
HP:0000488	Retinopathy
HP:0000499	Abnormal eyelash morphology
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000541	Retinal detachment
HP:0000554	Uveitis
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000622	Blurred vision
HP:0000708	Atypical behavior
HP:0000737	Irritability
HP:0000854	Thyroid adenoma
HP:0000978	Bruising susceptibility
HP:0001025	Urticaria
HP:0001045	Vitiligo
HP:0001053	Hypopigmented skin patches
HP:0001061	Acne
HP:0001094	Iridocyclitis
HP:0001097	Keratoconjunctivitis sicca
HP:0001250	Seizure
HP:0001251	Ataxia

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000763_3	Immunoglobulin A	6.000000e-06
GCST000852_5	Atrioventricular conduction	7.000000e-07
GCST001762_158	Obesity-related traits	7.000000e-06
GCST001762_384	Obesity-related traits	5.000000e-06
GCST001762_542	Obesity-related traits	9.000000e-06
GCST001762_634	Obesity-related traits	7.000000e-06
GCST002073_3	Chronic lymphocytic leukemia	1.000000e-14
GCST002299_13	Chronic lymphocytic leukemia	2.000000e-08
GCST003468_11	Chronic lymphocytic leukemia	9.000000e-14
GCST003814_2	Selective IgA deficiency	7.000000e-08
GCST004146_14	Chronic lymphocytic leukemia	1.000000e-15
GCST004863_8	Mosquito bite size	2.000000e-06
GCST005528_22	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	3.000000e-08
GCST005547_15	Major depressive disorder	2.000000e-06
GCST006585_1308	Blood protein levels	4.000000e-18
GCST006585_2678	Blood protein levels	3.000000e-06
GCST006585_565	Blood protein levels	2.000000e-24
GCST006585_586	Blood protein levels	3.000000e-21
GCST007844_16	Ankylosing spondylitis	5.000000e-06
GCST008863_1	Malate levels	1.000000e-07
GCST009731_57	Blood protein levels in cardiovascular risk	2.000000e-28
GCST010002_133	Refractive error	2.000000e-50
GCST90002392_619	Mean corpuscular volume	4.000000e-12
GCST90002397_543	Mean spheric corpuscular volume	1.000000e-12
GCST90002403_270	Red blood cell count	4.000000e-13

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004747	protein measurement
EFO:0004338	body weight
EFO:0004340	body mass index
EFO:0008378	mosquito bite reaction size measurement
EFO:0010508	malate measurement
EFO:0010610	tumor necrosis factor receptor superfamily member 6 measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D056735	Autoimmune Lymphoproliferative Syndrome	C15.604.515.138; C16.320.089; C20.111.288; C20.683.515.124
D004948	Esotropia	C10.292.562.887.300; C11.590.810.400
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D018197	Hepatoblastoma	C04.557.435.380
D065886	Neurodevelopmental Disorders	F03.625
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C567085	Aortic Aneurysm, Familial Thoracic 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4106134 (PROTEIN COMPLEX), CHEMBL4158 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 188,980 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1219	RABEPRAZOLE	4	12,441
CHEMBL1502	PANTOPRAZOLE	4	14,689
CHEMBL1503	OMEPRAZOLE	4	52,284
CHEMBL175247	ORLISTAT	4	38,186
CHEMBL480	LANSOPRAZOLE	4	24,317
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL3661754	DENIFANSTAT	2	736

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2234767	ACTA2, FAS		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 2.3.1.- Acyltransferases

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
GSK2194069	Inhibition	8.11	pIC50
denifanstat	Inhibition	7.28	pIC50
orlistat	Inhibition	5.87	pIC50

Binding affinities (BindingDB)

987 measured of 1155 human assays (1156 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[[(3S)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-4-(2-fluoro-4-isoquinolin-6-ylphenyl)-1H-1,2,4-triazol-5-one	IC50	3 nM	US-8802864: Triazolones as fatty acid synthase inhibitors
3-[[(3S)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-4-[4-(1H-indol-6-yl)-2-methylphenyl]-1H-1,2,4-triazol-5-one	IC50	5 nM	US-8802864: Triazolones as fatty acid synthase inhibitors
4-[1-[3-(5-chloro-2-methyl-1H-imidazol-4-yl)-4-methylbenzoyl]piperidin-4-yl]benzonitrile	IC50	5 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[4-(1-benzofuran-6-yl)phenyl]-3-[[(3S)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-1H-1,2,4-triazol-5-one	IC50	6 nM	US-8802864: Triazolones as fatty acid synthase inhibitors
4-[1-[3-(5-chloro-2-methyl-1H-imidazol-4-yl)-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	6 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-(5-chloro-2-methyl-1H-imidazol-4-yl)-4-methylbenzoyl]-4-fluoropiperidin-4-yl]benzonitrile	IC50	6 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-(5-chloro-2-cyclopropyl-1H-imidazol-4-yl)-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	7 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-(5-chloro-2-cyclopropyl-1H-imidazol-4-yl)-4-methylbenzoyl]piperidin-4-yl]benzonitrile	IC50	7 nM	US-9428502: Heterocyclic modulators of lipid synthesis
methyl 3-[4-[5-[3-(4-cyanophenyl)azetidine-1-carbonyl]-2-methylphenyl]-5-methyl-1H-imidazol-2-yl]azetidine-1-carboxylate	IC50	8 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-[5-chloro-2-(methoxymethyl)-1H-imidazol-4-yl]-4-methylbenzoyl]piperidin-4-yl]benzonitrile	IC50	9 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-(5-chloro-2-propan-2-yl-1H-imidazol-4-yl)-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	9 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-(5-chloro-2-cyclopropyl-1H-imidazol-4-yl)-4-methylbenzoyl]-4-fluoropiperidin-4-yl]benzonitrile	IC50	9 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-(5-chloro-2-propan-2-yl-1H-imidazol-4-yl)-4-methylbenzoyl]piperidin-4-yl]benzonitrile	IC50	9 nM	US-9428502: Heterocyclic modulators of lipid synthesis
methyl 4-[4-[5-[3-(4-cyanophenyl)azetidine-1-carbonyl]-2-methylphenyl]-5-methyl-1H-imidazol-2-yl]piperidine-1-carboxylate	IC50	9 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-[5-chloro-2-(oxan-4-yl)-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	9 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-[5-chloro-2-(2-hydroxyethyl)-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	9 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-[2-(4-methoxycyclohexyl)-5-(trifluoromethyl)-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	9 nM	US-9428502: Heterocyclic modulators of lipid synthesis
(S)-4-(4-(Benzofuran-5-yl)phenyl)-3-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)methyl)-1H-1,2,4-triazol-5(4H)-one	IC50	10 nM	US-8802864: Triazolones as fatty acid synthase inhibitors
4-[1-[4-cyclobutyl-2-methyl-5-(3,4,6,7-tetrahydropyrano[3,4-d]imidazol-2-yl)benzoyl]-4-fluoropiperidin-4-yl]benzonitrile	IC50	10 nM	US-8871790: Heterocyclic modulators of lipid synthesis
methyl 2-[5-[4-(4-cyanophenyl)-4-fluoropiperidine-1-carbonyl]-2-cyclobutyl-4-methylphenyl]-3,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylate	IC50	10 nM	US-8871790: Heterocyclic modulators of lipid synthesis
methyl 2-[5-[4-(4-cyanophenyl)piperidine-1-carbonyl]-2-cyclobutylphenyl]-3,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylate	IC50	10 nM	US-8871790: Heterocyclic modulators of lipid synthesis
4-[1-[3-(2,5-dimethyl-1H-imidazol-4-yl)-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	10 nM	US-9428502: Heterocyclic modulators of lipid synthesis
5-[5-[3-(4-cyanophenyl)azetidine-1-carbonyl]-2-methylphenyl]-2-cyclopropyl-1H-imidazole-4-carbonitrile	IC50	10 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-[2-cyclopropyl-5-(hydroxymethyl)-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	10 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-[2-(4-hydroxycyclohexyl)-5-methyl-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	10 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[5-(5-chloro-2-methyl-1H-imidazol-4-yl)-2,4-dimethylbenzoyl]azetidin-3-yl]benzonitrile	IC50	11 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[4-methyl-3-[5-methyl-2-(oxan-4-yl)-1H-imidazol-4-yl]benzoyl]azetidin-3-yl]benzonitrile	IC50	11 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[4-methyl-3-[5-methyl-2-(oxolan-3-yl)-1H-imidazol-4-yl]benzoyl]azetidin-3-yl]benzonitrile	IC50	11 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[4-methyl-3-[5-methyl-2-(3-methyloxetan-3-yl)-1H-imidazol-4-yl]benzoyl]azetidin-3-yl]benzonitrile	IC50	11 nM	US-9428502: Heterocyclic modulators of lipid synthesis
5-[5-[3-(4-cyanophenyl)azetidine-1-carbonyl]-2-methylphenyl]-2-(oxan-4-yl)-1H-imidazole-4-carbonitrile	IC50	11 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-[2-(2-cyanoethyl)-5-methyl-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	11 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-[2-(2-hydroxyethyl)-5-(trifluoromethyl)-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	11 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-[2-(2-methoxyethyl)-5-(trifluoromethyl)-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	11 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[5-(5-chloro-2-methyl-1H-imidazol-4-yl)-2,4-dimethylbenzoyl]piperidin-4-yl]benzonitrile	IC50	12 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-(5-chloro-2-cyclopropyl-1H-imidazol-4-yl)-4-methylbenzoyl]-3-fluoroazetidin-3-yl]benzonitrile	IC50	12 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-[2-(2-hydroxyethyl)-5-methyl-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	12 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-[2-(methoxymethyl)-5-(trifluoromethyl)-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	12 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[3-fluoro-1-[4-methyl-3-[2-methyl-5-(trifluoromethyl)-1H-imidazol-4-yl]benzoyl]azetidin-3-yl]benzonitrile	IC50	12 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[2,4-dimethyl-5-[2-methyl-5-(trifluoromethyl)-1H-imidazol-4-yl]benzoyl]-3-fluoroazetidin-3-yl]benzonitrile	IC50	12 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-(2,5-dimethyl-1H-imidazol-4-yl)-4-pyrrolidin-1-ylbenzoyl]azetidin-3-yl]benzonitrile	IC50	12 nM	US-9428502: Heterocyclic modulators of lipid synthesis
3-[[(3S)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-4-[4-(1-methylbenzimidazol-5-yl)phenyl]-1H-1,2,4-triazol-5-one	IC50	13 nM	US-8802864: Triazolones as fatty acid synthase inhibitors
4-[1-[3-[2-(4-hydroxyoxan-4-yl)-5-methyl-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	13 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-[5-chloro-2-(2-methoxyethyl)-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	13 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-[2-(4-methoxycyclohexyl)-5-(trifluoromethyl)-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	13 nM	US-9428502: Heterocyclic modulators of lipid synthesis
5-[5-[3-(4-cyanophenyl)azetidine-1-carbonyl]-2-methylphenyl]-2-(oxolan-3-yl)-1H-imidazole-4-carbonitrile	IC50	14 nM	US-9428502: Heterocyclic modulators of lipid synthesis
methyl 4-[5-chloro-4-[5-[3-(4-cyanophenyl)azetidine-1-carbonyl]-2-methylphenyl]-1H-imidazol-2-yl]-4-methylpiperidine-1-carboxylate	IC50	14 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[3-[5-chloro-2-(methoxymethyl)-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	14 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[2,4-dimethyl-5-[2-methyl-5-(trifluoromethyl)-1H-imidazol-4-yl]benzoyl]azetidin-3-yl]benzonitrile	IC50	14 nM	US-9428502: Heterocyclic modulators of lipid synthesis
4-[1-[2,4-dimethyl-5-(6-pyrrolidin-1-yl-3H-imidazo[4,5-c]pyridin-2-yl)benzoyl]-4-fluoropiperidin-4-yl]benzonitrile	IC50	15 nM	US-8871790: Heterocyclic modulators of lipid synthesis
4-[1-[3-[2-(3-methoxyoxan-3-yl)-5-methyl-1H-imidazol-4-yl]-4-methylbenzoyl]azetidin-3-yl]benzonitrile	IC50	15 nM	US-9428502: Heterocyclic modulators of lipid synthesis

ChEMBL bioactivities

1536 potent at pChembl≥5 of 1628 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	IC50	3	nM	CHEMBL3623457
8.52	IC50	3	nM	CHEMBL3646811
8.30	IC50	5	nM	CHEMBL3646807
8.30	IC50	5	nM	CHEMBL3962197
8.22	IC50	6	nM	CHEMBL2147033
8.22	IC50	6	nM	CHEMBL3623460
8.22	IC50	6	nM	CHEMBL3646804
8.22	IC50	6	nM	CHEMBL3975955
8.22	IC50	6	nM	CHEMBL3915660
8.15	IC50	7	nM	CHEMBL3949918
8.15	IC50	7	nM	CHEMBL3968803
8.11	IC50	7.7	nM	CHEMBL3646801
8.10	IC50	7.9	nM	CHEMBL3623458
8.10	IC50	8	nM	CHEMBL3979428
8.05	IC50	9	nM	CHEMBL3927497
8.05	IC50	9	nM	CHEMBL3975941
8.05	IC50	9	nM	CHEMBL3940149
8.05	IC50	9	nM	CHEMBL3945625
8.05	IC50	9	nM	CHEMBL3960666
8.05	IC50	9	nM	CHEMBL3895704
8.05	IC50	9	nM	CHEMBL3922048
8.05	IC50	9	nM	CHEMBL3936614
8.00	IC50	10	nM	CHEMBL2147032
8.00	IC50	10	nM	CHEMBL3623461
8.00	IC50	10	nM	CHEMBL3646801
8.00	IC50	10	nM	CHEMBL3666601
8.00	IC50	10	nM	CHEMBL3666606
8.00	IC50	10	nM	CHEMBL3666615
8.00	IC50	10	nM	CHEMBL3905299
8.00	IC50	10	nM	CHEMBL3906251
8.00	IC50	10	nM	CHEMBL3935073
8.00	IC50	10	nM	CHEMBL3891794
8.00	IC50	10	nM	CHEMBL4450081
7.96	IC50	11	nM	CHEMBL3902171
7.96	IC50	11	nM	CHEMBL3927676
7.96	IC50	11	nM	CHEMBL3936277
7.96	IC50	11	nM	CHEMBL3977044
7.96	IC50	11	nM	CHEMBL3908611
7.96	IC50	11	nM	CHEMBL3940947
7.96	IC50	11	nM	CHEMBL3894044
7.96	IC50	11	nM	CHEMBL3938270
7.96	IC50	11	nM	CHEMBL4462401
7.96	IC50	11	nM	CHEMBL4553437
7.92	IC50	12	nM	CHEMBL2322360
7.92	IC50	12	nM	CHEMBL3973206
7.92	IC50	12	nM	CHEMBL3936004
7.92	IC50	12	nM	CHEMBL3986980
7.92	IC50	12	nM	CHEMBL3933162
7.92	IC50	12	nM	CHEMBL3971866
7.92	IC50	12	nM	CHEMBL3916409

PubChem BioAssay actives

230 with measured affinity, of 529 total; 50 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-[[(3S)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-4-(2-fluoro-4-isoquinolin-7-ylphenyl)-1H-1,2,4-triazol-5-one	1251224: Inhibition of fatty acid synthase (unknown origin)	ic50	0.0030	uM
4-cyclopropyl-9-(4-isoquinolin-5-ylphenyl)sulfonyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one	1251224: Inhibition of fatty acid synthase (unknown origin)	ic50	0.0060	uM
4-cyclopropyl-9-(4-isoquinolin-6-ylphenyl)sulfonyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one	689725: Inhibition of fatty acid synthase	ic50	0.0060	uM
4-[4-(1-benzofuran-5-yl)phenyl]-3-[[(3S)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-1H-1,2,4-triazol-5-one	1800376: FAS Assay No2 from Article 10.1038/nchembio.1603: “A human fatty acid synthase inhibitor binds ß-ketoacyl reductase in the keto-substrate site.”	ic50	0.0077	uM
5-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-6-[4-(1H-indol-5-yl)phenyl]-1-methylpyrazolo[5,4-d]pyrimidin-4-one	1251224: Inhibition of fatty acid synthase (unknown origin)	ic50	0.0079	uM
4-cyclopropyl-9-(4-quinolin-7-ylphenyl)sulfonyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one	689725: Inhibition of fatty acid synthase	ic50	0.0100	uM
6-[4-[(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)sulfonyl]piperazin-1-yl]naphthalene-2-carbonitrile	1251224: Inhibition of fatty acid synthase (unknown origin)	ic50	0.0100	uM
[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-(4-quinolin-3-ylphenyl)methanone	1602939: Inhibition of full length recombinant human FASN using acetyl-CoA/malonyl-CoA as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins in presence of NADPH	ic50	0.0100	uM
[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-(4-isoquinolin-6-ylphenyl)methanone	1602941: Inhibition of FASN in human BT474 cells preincubated for 1 hr followed by [14C]-acetate addition and measured after 4 hrs by scintillation counting assay	ic50	0.0110	uM
[4-(1,3-benzothiazol-5-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone	1602941: Inhibition of FASN in human BT474 cells preincubated for 1 hr followed by [14C]-acetate addition and measured after 4 hrs by scintillation counting assay	ic50	0.0110	uM
4-[1-[2,4-dimethyl-5-(6-pyrrolidin-1-yl-3H-imidazo[4,5-c]pyridin-2-yl)benzoyl]piperidin-4-yl]benzonitrile	727766: Inhibition of FASN in human HeLa cells assessed as reduction of de novo synthesis of palmitate	ic50	0.0120	uM
[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1-methylindol-5-yl)phenyl]methanone	1602939: Inhibition of full length recombinant human FASN using acetyl-CoA/malonyl-CoA as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins in presence of NADPH	ic50	0.0120	uM
cyclopropyl-[(3S)-3-[[3-[4-(1H-indazol-5-yl)phenyl]-1,2,4-triazol-4-yl]methyl]pyrrolidin-1-yl]methanone	1251224: Inhibition of fatty acid synthase (unknown origin)	ic50	0.0130	uM
1,3-bis[4-[(4-methylpyrimidin-2-yl)sulfamoyl]phenyl]urea	697034: Reversible inhibition of human recombinant FASN ketoreductase site	ic50	0.0158	uM
[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1H-indol-5-yl)phenyl]methanone	1602939: Inhibition of full length recombinant human FASN using acetyl-CoA/malonyl-CoA as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins in presence of NADPH	ic50	0.0160	uM
7-chloro-4-hydroxy-3-[3-(2-methoxyphenyl)phenyl]-2-oxo-1H-quinoline-6-carbonitrile	271417: Inhibition of human FAS	ic50	0.0190	uM
6-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-5-(4-isoquinolin-6-ylphenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0200	uM
6-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-5-(4-quinolin-7-ylphenyl)-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0200	uM
N-[[(3S)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-2-fluoro-4-(1H-indol-5-yl)-N-methylbenzamide	1251224: Inhibition of fatty acid synthase (unknown origin)	ic50	0.0200	uM
6-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-5-[2-fluoro-4-(1-methylindazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0220	uM
6-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-5-[4-(4-pyridin-4-ylphenyl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0230	uM
6-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-5-[4-(6-fluoronaphthalen-2-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0250	uM
[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1-methylindazol-6-yl)phenyl]methanone	1602939: Inhibition of full length recombinant human FASN using acetyl-CoA/malonyl-CoA as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins in presence of NADPH	ic50	0.0260	uM
5-[4-(1-benzofuran-5-yl)phenyl]-6-[[(3R)-1-(1-methylcyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0280	uM
6-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-5-[4-[4-(1-methylpyrazol-4-yl)phenyl]phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0280	uM
6-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-5-[4-(1-methylindazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0300	uM
2-[2-fluoro-4-[4-(1-methylpyrazol-4-yl)phenyl]phenyl]-3-[[(3R)-1-(1-hydroxycyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-5,5-dimethylimidazol-4-one	1246923: Inhibition of fatty acid synthase (unknown origin) by scintillation proximity assay	ic50	0.0302	uM
[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-(4-quinolin-2-ylphenyl)methanone	1602939: Inhibition of full length recombinant human FASN using acetyl-CoA/malonyl-CoA as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins in presence of NADPH	ic50	0.0320	uM
6-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-5-[4-(1H-indazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0320	uM
[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]-[4-(1-methylindol-2-yl)phenyl]methanone	1602939: Inhibition of full length recombinant human FASN using acetyl-CoA/malonyl-CoA as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins in presence of NADPH	ic50	0.0330	uM
6-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-5-[4-(1H-indazol-4-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0330	uM
5-[4-(4-cyanophenyl)piperidine-1-carbonyl]-2-methyl-N-(6-pyrrolidin-1-yl-3-pyridinyl)benzamide	727773: Inhibition of human FASN assessed as release of co-enzyme A	ic50	0.0350	uM
5-[4-(1-benzofuran-5-yl)phenyl]-6-[[(3R)-1-(1-hydroxycyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0360	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148373: Binding affinity to human FASN incubated for 45 mins by Kinobead based pull down assay	kd	0.0377	uM
4-[1-[2,4-dimethyl-5-(6-morpholin-4-yl-3H-imidazo[4,5-c]pyridin-2-yl)benzoyl]piperidin-4-yl]benzonitrile	727773: Inhibition of human FASN assessed as release of co-enzyme A	ic50	0.0400	uM
3-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-2-[4-(1H-indol-3-yl)phenyl]-5,5-dimethylimidazol-4-one	1251225: Inhibition of fatty acid synthase KR domain (unknown origin)	ic50	0.0410	uM
6-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-5-[4-(1H-indol-3-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0410	uM
5-[4-(1,3-benzothiazol-5-yl)phenyl]-6-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0420	uM
4-[1-[3-[6-(azetidin-1-yl)-3H-imidazo[4,5-c]pyridin-2-yl]-4-methylbenzoyl]piperidin-4-yl]benzonitrile	727773: Inhibition of human FASN assessed as release of co-enzyme A	ic50	0.0450	uM
5-[4-(1-benzofuran-5-yl)phenyl]-6-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0460	uM
3-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-2-[4-(1H-indol-5-yl)phenyl]-5,5-dimethylimidazol-4-one	1246923: Inhibition of fatty acid synthase (unknown origin) by scintillation proximity assay	ic50	0.0479	uM
5-[4-(3-chlorophenyl)phenyl]-6-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0500	uM
N-[5-[4-(4-cyanophenyl)piperidine-1-carbonyl]-2-methylphenyl]-6-pyrrolidin-1-ylpyridine-3-carboxamide	727773: Inhibition of human FASN assessed as release of co-enzyme A	ic50	0.0500	uM
6-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-5-[2-methyl-4-(1-methylindazol-5-yl)phenyl]-4,6-diazaspiro[2.4]hept-4-en-7-one	1496856: Inhibition of human full length FASN using [3H]-acetyl-CoA/malonyl-CoA as substrate after 60 mins in presence of NADPH by scintillation proximity assay	ic50	0.0510	uM
7-chloro-4-hydroxy-2-oxo-3-(3-phenylphenyl)-1H-quinoline-6-carbonitrile	271417: Inhibition of human FAS	ic50	0.0520	uM
[4-(1,3-benzoxazol-2-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone	1602939: Inhibition of full length recombinant human FASN using acetyl-CoA/malonyl-CoA as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins in presence of NADPH	ic50	0.0540	uM
7-chloro-3-[3-(4-fluorophenyl)phenyl]-4-hydroxy-2-oxo-1H-quinoline-6-carbonitrile	271417: Inhibition of human FAS	ic50	0.0540	uM
3-[[(3R)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]methyl]-5,5-dimethyl-2-(4-quinolin-7-ylphenyl)imidazol-4-one	1246923: Inhibition of fatty acid synthase (unknown origin) by scintillation proximity assay	ic50	0.0562	uM
[4-(1,3-benzothiazol-2-yl)phenyl]-[4-(1-hydroxycyclopropanecarbonyl)piperazin-1-yl]methanone	1602939: Inhibition of full length recombinant human FASN using acetyl-CoA/malonyl-CoA as substrate preincubated for 60 mins followed by substrate addition and measured after 90 mins in presence of NADPH	ic50	0.0570	uM
4-[1-[2-methyl-5-(6-pyrrolidin-1-yl-3H-imidazo[4,5-c]pyridin-2-yl)benzoyl]piperidin-4-yl]benzonitrile	727773: Inhibition of human FASN assessed as release of co-enzyme A	ic50	0.0600	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects cotreatment, increases methylation, decreases expression, affects reaction (+2 more)	14
Orlistat	decreases response to substance, decreases abundance, decreases chemical synthesis, affects binding, decreases reaction (+5 more)	14
Palmitic Acid	affects abundance, decreases expression, increases phosphorylation, decreases reaction, increases expression (+1 more)	10
T0901317	increases expression, affects cotreatment, decreases expression, decreases reaction	9
Valproic Acid	decreases expression, affects reaction, increases expression, affects cotreatment	9
Oleic Acid	affects expression, increases reaction, decreases reaction, increases expression, affects cotreatment (+1 more)	9
fatostatin	decreases expression, increases response to substance, increases reaction, affects cotreatment	8
Dexamethasone	affects cotreatment, increases expression, increases reaction, decreases response to substance, decreases reaction (+1 more)	6
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance, increases expression	5
Rosiglitazone	increases response to substance, affects cotreatment, decreases reaction, increases expression, decreases abundance (+2 more)	5
Resveratrol	decreases reaction, increases expression, decreases expression, increases abundance, increases activity	5
Benzo(a)pyrene	affects cotreatment, affects expression, decreases expression, increases expression	5
Quercetin	affects cotreatment, decreases reaction, increases expression, decreases expression	5
perfluorooctane sulfonic acid	decreases expression	4
Dichlorodiphenyl Dichloroethylene	affects cotreatment, increases expression, increases reaction, decreases expression	4
Fatty Acids	increases chemical synthesis, affects cotreatment, decreases abundance, decreases activity, decreases chemical synthesis (+2 more)	4
Fatty Acids, Nonesterified	increases expression, increases abundance, increases reaction, affects expression, decreases reaction	4
Metformin	affects cotreatment, decreases expression, decreases reaction, increases expression	4
Oxygen	decreases reaction, affects cotreatment, affects expression, increases expression, increases reaction (+1 more)	4
1-Methyl-3-isobutylxanthine	decreases reaction, affects expression, affects cotreatment, increases expression, increases reaction (+1 more)	4
Cyclosporine	affects cotreatment, affects expression, decreases expression, increases expression	4
nuciferine	decreases reaction, increases expression	3
mono-(2-ethylhexyl)phthalate	increases expression, affects expression	3
perfluorooctanoic acid	decreases expression, increases expression, affects cotreatment	3
perfluorobutyric acid	affects expression, increases expression, affects cotreatment, decreases expression	3
dorsomorphin	decreases reaction, increases expression, affects cotreatment, decreases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	3
Ethanol	affects cotreatment, decreases reaction, increases expression	3
Arsenic	affects expression, affects methylation, affects cotreatment, decreases expression, increases abundance	3
Cisplatin	increases response to substance, increases expression, affects cotreatment, decreases expression, decreases activity	3

ChEMBL screening assays

142 unique, capped per target: 136 binding, 6 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2090997	Binding	Inhibition of FASN/HER2 in human SK-BR-3 cells assessed as reduction in p-ERK1/2 levels after 6 hrs by Western blot analysis	New synthetic inhibitors of fatty acid synthase with anticancer activity. — J Med Chem
CHEMBL2114818	Functional	PubChem BioAssay. Dose response confirmation of uHTS inhibitor hits of the thioesterase domain of fatty acid synthase via a fluorescence intensity assay. (Class of assay: confirmatory)	PubChem BioAssay data set

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1WB	Abcam A-549 FASN KO	Cancer cell line	Male
CVCL_D2AQ	Abcam HCT 116 FASN KO	Cancer cell line	Male
CVCL_E0CZ	Ubigene HeLa FASN KO	Cancer cell line	Female
CVCL_E0WZ	Ubigene KYSE-30 FASN KO	Cancer cell line	Male
CVCL_SN16	HAP1 FASN (-) 1	Cancer cell line	Male
CVCL_SN17	HAP1 FASN (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00039858	PHASE4	COMPLETED	Evaluation of Argatroban Injection in Pediatric Patients Requiring Anticoagulant Alternatives to Heparin
NCT00239733	PHASE4	TERMINATED	Anti-D for Treating Thrombocytopenia in Adults Infected With Hepatitis C Virus With or Without HIV Co-Infection
NCT00907478	PHASE4	COMPLETED	Study on Bone Marrow Morphology in Adults Receiving Romiplostim for Treatment of Thrombocytopenia Associated With Immune Thrombocytopenia Purpura (ITP)
NCT01727401	PHASE4	TERMINATED	Thromboprophylaxis of Venous Thromboembolism in Acutely-ill Medical Inpatients With Thrombocytopenia
NCT02032134	PHASE4	TERMINATED	Protocol for the Infusion of Buffy Coat-derived Cryopreserved Platelets in Patients With Severe Thrombocytopenia
NCT02267993	PHASE4	COMPLETED	Efficacy and Safety of rhTPO for the Treatment of Thrombocytopenia After Chemotherapy in AML Patients
NCT03633019	PHASE4	UNKNOWN	High-dose Use of rhTPO in CIT Patients
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04906083	PHASE4	UNKNOWN	Avatrombopag in Patients With End-stage Liver Disease and Thrombocytopenia
NCT05217719	PHASE4	UNKNOWN	Effects of Recombinant Human Thrombopoietin on Platelet Levels in ICU Patients
NCT05255003	PHASE4	RECRUITING	STrategies for Anticoagulation in Patients With thRombocytopenia and Cancer-associated Thrombosis
NCT05382013	PHASE4	UNKNOWN	Efficacy and Safety of Avatrombopag for Treating TCP in HBV-ACLF Patients Receiving ALSS Treatment
NCT05944458	PHASE4	COMPLETED	Efficacy of Intravenous N-Acetylcysteine in Preventing Linezolid-Induced Thrombocytopenia in Critically Ill Patients
NCT06562738	PHASE4	RECRUITING	Clinical Study on Efficacy and Safety of Hetrombopag in the Preoperative Patients of Thrombocytopenia
NCT01460355	PHASE4	COMPLETED	Comparison of Two Treatments for Strabismus Correction: Botulinum Toxin A Associated to Surgery and Surgery Alone
NCT06077682	PHASE4	UNKNOWN	Cycloplegic Refraction in Pediatric Patients With Esotropia
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00037791	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00039910	PHASE3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00073580	PHASE3	COMPLETED	Angiomax in Patients With HIT/HITTS Type II Undergoing Off-Pump Coronary Artery Bypass Grafting (CABG) (CHOOSE)
NCT00102323	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Refractory to Splenectomy
NCT00102336	PHASE3	COMPLETED	AMG 531 Treatment of Thrombocytopenic Subjects With Immune (Idiopathic) Thrombocytopenic Purpura (ITP) Prior to Splenectomy
NCT00116688	PHASE3	COMPLETED	Open Label Extension Study of Romiplostim (AMG 531) in Thrombocytopenic Patients With Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
NCT00128713	PHASE3	COMPLETED	Optimal Platelet Dose Strategy for Management of Thrombocytopenia
NCT00151866	PHASE3	COMPLETED	Efficacy of Transfusions With Platelets Stored in Platelet Additive Solution II Versus Plasma
NCT00261924	PHASE3	COMPLETED	Efficacy and Safety Study of Platelets Treated for Pathogen Inactivation and Stored for Up to Seven Days
NCT00415532	PHASE3	COMPLETED	Romiplostim (AMG 531) Versus Medical Standard of Care for Immune (Idiopathic) Thrombocytopenic Purpura
NCT00420914	PHASE3	TERMINATED	Strategies for Transfusion of Platelets (SToP)
NCT00501345	PHASE3	TERMINATED	Aspirin in Patients With Myocardial Infarction and Thrombocytopenia
NCT00508820	PHASE3	COMPLETED	An Open Label Study of Romiplostim in Adult Thrombocytopenic Subjects With ITP