FDFT1

Summary

FDFT1 (farnesyl-diphosphate farnesyltransferase 1, HGNC:3629) is a protein-coding gene on chromosome 8p23.1, encoding Squalene synthase (P37268). Catalyzes the condensation of 2 farnesyl pyrophosphate (FPP) moieties to form squalene. It is a selective cancer dependency (DepMap: 10.0% of cell lines).

This gene encodes a membrane-associated enzyme located at a branch point in the mevalonate pathway. The encoded protein is the first specific enzyme in cholesterol biosynthesis, catalyzing the dimerization of two molecules of farnesyl diphosphate in a two-step reaction to form squalene.

Source: NCBI Gene 2222 — RefSeq curated summary.

At a glance

• Gene–disease (curated): squalene synthase deficiency (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 46
• Clinical variants (ClinVar): 172 total — 3 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 37
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 10.0% of screened cell lines
• MANE Select transcript: NM_004462

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3629
Approved symbol	FDFT1
Name	farnesyl-diphosphate farnesyltransferase 1
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	SQS
Ensembl gene	ENSG00000079459
Ensembl biotype	protein_coding
OMIM	184420
Entrez	2222

Gene structure

Transcript identifiers

Ensembl transcripts: 49 — 39 protein_coding, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000220584, ENST00000443614, ENST00000446331, ENST00000525283, ENST00000525551, ENST00000525571, ENST00000525607, ENST00000525900, ENST00000525954, ENST00000527045, ENST00000528643, ENST00000528729, ENST00000528812, ENST00000529464, ENST00000529521, ENST00000530337, ENST00000530664, ENST00000531733, ENST00000532266, ENST00000615631, ENST00000622850, ENST00000866105, ENST00000866106, ENST00000866107, ENST00000866108, ENST00000866109, ENST00000866110, ENST00000938346, ENST00000938347, ENST00000938348, ENST00000938349, ENST00000938350, ENST00000938351, ENST00000938352, ENST00000938353, ENST00000938354, ENST00000938355, ENST00000938356, ENST00000938357, ENST00000938358, ENST00000938359, ENST00000938360, ENST00000938361, ENST00000938362, ENST00000938363, ENST00000938364, ENST00000938365, ENST00000941570, ENST00000941571

RefSeq mRNA: 11 — MANE Select: NM_004462 NM_001287742, NM_001287743, NM_001287744, NM_001287745, NM_001287747, NM_001287748, NM_001287749, NM_001287750, NM_001287751, NM_001287756, NM_004462

CCDS: CCDS5985, CCDS75696, CCDS75697, CCDS87579

Canonical transcript exons

ENST00000220584 — 8 exons

Exon	Start	End
ENSE00001323254	11838388	11839298
ENSE00002193497	11802741	11802931
ENSE00003470002	11826024	11826215
ENSE00003483410	11809667	11809850
ENSE00003538514	11830244	11830420
ENSE00003550057	11821750	11821878
ENSE00003552359	11831518	11831670
ENSE00003627695	11808794	11808891

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 99.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 170.1171 / max 1546.4089, expressed in 1827 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87423	158.5721	1827
87425	9.3373	1324
87420	0.8722	322
87424	0.7856	393
87421	0.2355	154
87426	0.1217	48
205072	0.0830	31
205074	0.0691	28
205073	0.0356	7
205071	0.0051	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
embryo	UBERON:0000922	99.44	gold quality
ganglionic eminence	UBERON:0004023	99.44	gold quality
adrenal tissue	UBERON:0018303	99.28	gold quality
ventricular zone	UBERON:0003053	99.25	gold quality
cortical plate	UBERON:0005343	99.00	gold quality
mucosa of transverse colon	UBERON:0004991	98.62	gold quality
left testis	UBERON:0004533	98.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.39	gold quality
right testis	UBERON:0004534	98.36	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.34	gold quality
minor salivary gland	UBERON:0001830	98.13	gold quality
right adrenal gland	UBERON:0001233	97.96	gold quality
islet of Langerhans	UBERON:0000006	97.90	gold quality
right adrenal gland cortex	UBERON:0035827	97.90	gold quality
right lung	UBERON:0002167	97.81	gold quality
skin of abdomen	UBERON:0001416	97.72	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	97.59	gold quality
body of stomach	UBERON:0001161	97.57	gold quality
skin of leg	UBERON:0001511	97.56	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.54	gold quality
rectum	UBERON:0001052	97.48	gold quality
transverse colon	UBERON:0001157	97.43	gold quality
left adrenal gland	UBERON:0001234	97.33	gold quality
upper lobe of left lung	UBERON:0008952	97.03	gold quality
left adrenal gland cortex	UBERON:0035825	97.01	gold quality
gastrocnemius	UBERON:0001388	96.98	gold quality
esophagus mucosa	UBERON:0002469	96.89	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.82	gold quality
ectocervix	UBERON:0012249	96.78	gold quality
muscle of leg	UBERON:0001383	96.77	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1225.14
E-HCAD-5	no	19.60
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, NFYA, NR0B1, NR1H3, SREBF1, SREBF2

miRNA regulators (miRDB)

79 targeting FDFT1, 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-6873-3P	100.00	71.42	2626
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 10.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 22)

• Results report the high-resolution x-ray structures of human farnesyl pyrophosphate synthase in complexes with risedronate and zoledronate, two of the leading nitrogen-containing bisphosphonates in clinical use. (PMID:16684881)
• in prostate cancer cells SQS expression is enhanced by androgens, channeling intermediates of the mevalonate/isoprenoid pathway toward cholesterol synthesis (PMID:17483544)
• lysine in codon 45 is conserved across 11 mammals and lies in an exonic splicing enhancer site, suggesting this coding variant in the squalene synthase gene influences plasma cholesterol levels, by affecting the intracellular production of cholesterol (PMID:18350552)
• the liver X receptor alpha directly silencing the expression of two key cholesterologenic enzymes (lanosterol 14alpha-demethylase (CYP51A1), and squalene synthase (farnesyl diphosphate farnesyl transferase 1)) via novel negative LXR DNA response elements (PMID:18676367)
• squalene synthase may be involved in the etiology of hypercholesterolemia (PMID:19054015)
• FDFT1 rs7001819 showed no association with obesity, neither when analysing quantitative traits nor when performing case-control studies of obesity (PMID:19245693)
• In multivariate models adjusted for age, body mass index, diabetes, waist/hip ratios, and levels of glycated hemoglobin, the NAFLD activity score was associated with the SNP rs2645424 on chromosome 8 in farnesyl diphosphate farnesyl transferase 1 (FDFT1) (PMID:20708005)
• NASH is intimately related to fibrosis progression, the FDFT1 SNP is a good candidate for a link with inflammation and fibrosis. (PMID:21439984)
• CTSB and FDFT1 are excluded as candidates for keratolytic winter erythema (PMID:21945151)
• FDFT1 and its encoded enzyme, squalene synthase, may play an important role in prostate cancer development and its aggressive phenotypes. (PMID:22546838)
• ABHD5, PGRMC1 and SQS are novel markers for sebaceous carcinoma and can reliably distinguish sebaceous neoplasms from non-sebaceous tumors, specifically BCC with clear cell features. (PMID:23557589)
• The minor allele in FDFT1 was associated with advanced fibrosis in the non-steatotic but not in the steatotic subgroup in patients with chronic hepatitis C. (PMID:23870067)
• this finding yields a new method of colorimetric screening for the cellular activity of squalene synthases, which are major targets for cholesterol-lowering drugs. (PMID:24333579)
• Several critical residues that are involved in binding of NADPH have been identified in the active site of squalene synthase. (PMID:24531458)
• HCV infection increases FDFT1 protein level but not FDFT1 mRNA level. (PMID:24690320)
• Up-regulation of SQS promotes metastasis of lung cancer by enhancing tumor necrosis factor-alpha receptor 1 and nuclear factor-kappaB activation and matrix metallopeptidase 1 expression. (PMID:25152164)
• The results indicate that the ennea-peptide CLSPHSMFC, tetra-peptides SMFC, CKTE, and WHQW can effectively inhibit Squalene Synthase activities (IC50 values equal to 64, 76, 87, and 90 muM, respectively) (PMID:26922723)
• We have demonstrated the differential relative expression levels of FDFT1 mRNA and protein in various types of cancer based on TMAs and IHC for protein expression, and qPCR analysis for the illustration of mRNA expression. (PMID:30468409)
• Ubiquitin specific peptidase 32 acts as an oncogene in epithelial ovarian cancer by deubiquitylating farnesyl-diphosphate farnesyltransferase 1. (PMID:33744759)
• Squalene synthase predicts poor prognosis in stage I-III colon adenocarcinoma and synergizes squalene epoxidase to promote tumor progression. (PMID:34939274)
• Intramembrane protease SPP defines a cholesterol-regulated abundance control of the mevalonate pathway enzyme squalene synthase. (PMID:38218226)
• Spectroscopic diagnosis and metabolite characterization of cisplatin resistance regulated by FDFT1 in bladder cancer tissue. (PMID:38810354)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fdft1	ENSDARG00000101062
mus_musculus	Fdft1	ENSMUSG00000021273
rattus_norvegicus	Fdft1	ENSRNOG00000021314

Protein

Protein identifiers

Squalene synthase — P37268 (reviewed: P37268)

Alternative names: FPP:FPP farnesyltransferase, Farnesyl-diphosphate farnesyltransferase, Farnesyl-diphosphate farnesyltransferase 1

All UniProt accessions (10): P37268, A0A1W2PQ47, A0AA34QVU5, E9PJG4, E9PNJ2, E9PNM1, E9PQ90, E9PS69, E9PSH1, Q6IAX1

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the condensation of 2 farnesyl pyrophosphate (FPP) moieties to form squalene. Proceeds in two distinct steps. In the first half-reaction, two molecules of FPP react to form the stable presqualene diphosphate intermediate (PSQPP), with concomitant release of a proton and a molecule of inorganic diphosphate. In the second half-reaction, PSQPP undergoes heterolysis, isomerization, and reduction with NADPH or NADH to form squalene. It is the first committed enzyme of the sterol biosynthesis pathway.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed.

Disease relevance. Squalene synthase deficiency (SQSD) [MIM:618156] An autosomal recessive disorder characterized by profound developmental delay, brain abnormalities, 2/3 syndactyly of the toes, facial dysmorphisms, low total and LDL-cholesterol, and abnormal urine organic acids. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Terpene metabolism; lanosterol biosynthesis; lanosterol from farnesyl diphosphate: step 1/3.

Similarity. Belongs to the phytoene/squalene synthase family.

Isoforms (5)

UniProt ID	Names	Canonical?
P37268-1	1	yes
P37268-2	2
P37268-3	3
P37268-4	4
P37268-5	5

RefSeq proteins (11): NP_001274671, NP_001274672, NP_001274673, NP_001274674, NP_001274676, NP_001274677, NP_001274678, NP_001274679, NP_001274680, NP_001274685, NP_004453* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002060	Squ/phyt_synthse	Family
IPR006449	Squal_synth-like	Family
IPR008949	Isoprenoid_synthase_dom_sf	Homologous_superfamily
IPR019845	Squalene/phytoene_synthase_CS	Conserved_site
IPR033904	Trans_IPPS_HH	Domain
IPR044844	Trans_IPPS_euk-type	Family

Pfam: PF00494

Enzyme classification (BRENDA):

• EC 2.5.1.21 — squalene synthase (BRENDA: 49 organisms, 61 substrates, 208 inhibitors, 29 Km, 8 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NADPH	0.004–0.5	9
FARNESYL DIPHOSPHATE	0.0004–0.0095	7
(2E,6E)-FARNESYL DIPHOSPHATE	0.0038–0.061	5
NADH	0.004–3.6	2
TRANS-FARNESYL DIPHOSPHATE	0.001	1

Catalyzed reactions (Rhea), 5 shown:

• presqualene diphosphate + NADH + H(+) = squalene + diphosphate + NAD(+) (RHEA:22228)
• presqualene diphosphate + NADPH + H(+) = squalene + diphosphate + NADP(+) (RHEA:22232)
• 2 (2E,6E)-farnesyl diphosphate = presqualene diphosphate + diphosphate (RHEA:22672)
• 2 (2E,6E)-farnesyl diphosphate + NADPH + H(+) = squalene + 2 diphosphate + NADP(+) (RHEA:32295)
• 2 (2E,6E)-farnesyl diphosphate + NADH + H(+) = squalene + 2 diphosphate + NAD(+) (RHEA:32299)

UniProt features (47 total): helix 24, binding site 8, splice variant 4, transmembrane region 2, sequence variant 2, sequence conflict 2, turn 2, strand 2, chain 1

Structure

Experimental structures (PDB)

32 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6PYW	X-RAY DIFFRACTION	1.38
6PYJ	X-RAY DIFFRACTION	1.44
6PYV	X-RAY DIFFRACTION	1.45
3VJ8	X-RAY DIFFRACTION	1.52
3VJ9	X-RAY DIFFRACTION	1.52
6PZ5	X-RAY DIFFRACTION	1.53
3WEG	X-RAY DIFFRACTION	1.75
3VJA	X-RAY DIFFRACTION	1.76
3WEI	X-RAY DIFFRACTION	1.79
3V66	X-RAY DIFFRACTION	1.8
3WEK	X-RAY DIFFRACTION	1.85
3WEH	X-RAY DIFFRACTION	1.87
3VJC	X-RAY DIFFRACTION	1.89
3ASX	X-RAY DIFFRACTION	2
3Q2Z	X-RAY DIFFRACTION	2
3Q30	X-RAY DIFFRACTION	2
3WEJ	X-RAY DIFFRACTION	2
8WTQ	X-RAY DIFFRACTION	2
8WTR	X-RAY DIFFRACTION	2
3VJB	X-RAY DIFFRACTION	2.05
3WCM	X-RAY DIFFRACTION	2.06
1EZF	X-RAY DIFFRACTION	2.15
3WCJ	X-RAY DIFFRACTION	2.2
3WCF	X-RAY DIFFRACTION	2.22
3WCL	X-RAY DIFFRACTION	2.24
3WCI	X-RAY DIFFRACTION	2.3
3WEF	X-RAY DIFFRACTION	2.35
3WCH	X-RAY DIFFRACTION	2.5
3WCD	X-RAY DIFFRACTION	2.75
3WC9	X-RAY DIFFRACTION	2.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P37268-F1	89.14	0.74

Functional residue map

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

Ligand- & substrate-binding residues (8): 317; 52; 77; 80; 83; 84; 218; 315

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-9969896	Lanosterol biosynthesis
R-HSA-191273	Cholesterol biosynthesis

MSigDB gene sets: 389 (showing top): HORIUCHI_WTAP_TARGETS_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, JI_RESPONSE_TO_FSH_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MODULE_16, PUJANA_CHEK2_PCC_NETWORK, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, KOKKINAKIS_METHIONINE_DEPRIVATION_96HR_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_STEROID_BIOSYNTHETIC_PROCESS, KOKKINAKIS_METHIONINE_DEPRIVATION_48HR_UP, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN

GO Biological Process (10): steroid biosynthetic process (GO:0006694), cholesterol biosynthetic process (GO:0006695), farnesyl diphosphate metabolic process (GO:0045338), lipid metabolic process (GO:0006629), steroid metabolic process (GO:0008202), cholesterol metabolic process (GO:0008203), lipid biosynthetic process (GO:0008610), hexose transmembrane transport (GO:0008645), biosynthetic process (GO:0009058), sterol biosynthetic process (GO:0016126)

GO Molecular Function (7): metal ion binding (GO:0046872), squalene synthase [NAD(P)H] activity (GO:0051996), catalytic activity (GO:0003824), protein binding (GO:0005515), transferase activity (GO:0016740), transferase activity, transferring alkyl or aryl (other than methyl) groups (GO:0016765), D-glucose transmembrane transporter activity (GO:0055056)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Regulation of lipid metabolism by PPARalpha	1
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Cholesterol biosynthesis	1
Metabolism of steroids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	2
sterol metabolic process	2
steroid metabolic process	1
lipid biosynthetic process	1
cholesterol metabolic process	1
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
phospholipid metabolic process	1
terpenoid metabolic process	1
primary metabolic process	1
secondary alcohol metabolic process	1
biosynthetic process	1
monosaccharide transmembrane transport	1
metabolic process	1
steroid biosynthetic process	1
cation binding	1
prenyltransferase activity	1
molecular_function	1
binding	1
catalytic activity	1
transferase activity	1
hexose transmembrane transporter activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2902 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FDFT1	LSS	P48449	968
FDFT1	HMGCS1	Q01581	945
FDFT1	SQLE	Q14534	939
FDFT1	HMGCR	P04035	926
FDFT1	MSMO1	Q15800	917
FDFT1	FDPS	P14324	910
FDFT1	DHCR7	Q9UBM7	906
FDFT1	HMGCS2	P54868	901
FDFT1	CYP51A1	Q16850	896
FDFT1	SC5D	O75845	876
FDFT1	GGPS1	O95749	873
FDFT1	NSDHL	Q15738	847
FDFT1	MVK	Q03426	843
FDFT1	IDI1	Q13907	842
FDFT1	HSD17B7	P56937	839

IntAct

152 interactions, top by confidence:

A	B	Type	Score
HRAS	MTHFD2	psi-mi:“MI:0914”(association)	0.730
P2RX4	FAM20B	psi-mi:“MI:0914”(association)	0.640
FAM174A	GAK	psi-mi:“MI:0914”(association)	0.640
FDFT1	CREB3	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	CD79A	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	JAGN1	psi-mi:“MI:0915”(physical association)	0.560
CD74	FDFT1	psi-mi:“MI:0915”(physical association)	0.560
CLN5	FDFT1	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	ELOVL4	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	TLCD4	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	SLC35C2	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	FAM209A	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	PANX1	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	AQP6	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	GPR152	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	NCAPH2	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	TMX2	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	ARL13B	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	GJA8	psi-mi:“MI:0915”(physical association)	0.560
CD79A	FDFT1	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	USP32	psi-mi:“MI:0914”(association)	0.530
P2RX1	ATE1	psi-mi:“MI:0914”(association)	0.530
SRPRB	CTDNEP1	psi-mi:“MI:0914”(association)	0.530
STK32C	FDFT1	psi-mi:“MI:0914”(association)	0.530

BioGRID (195): FDFT1 (Affinity Capture-MS), FDFT1 (Affinity Capture-MS), FDFT1 (Affinity Capture-MS), FDFT1 (Affinity Capture-MS), FDFT1 (Affinity Capture-MS), FDFT1 (Affinity Capture-MS), FDFT1 (Affinity Capture-MS), FDFT1 (Affinity Capture-MS), FDFT1 (Affinity Capture-Western), CREB3 (Two-hybrid), FDFT1 (Affinity Capture-MS), FDFT1 (Affinity Capture-MS), USP32 (Affinity Capture-MS), UNC93B1 (Affinity Capture-MS), CNNM1 (Affinity Capture-MS)

ESM2 similar proteins: A0A142ZC57, A0A144YEA5, A0A169T193, A0A1D8PI71, A0A1L9WQI2, A0A1P7Y0A2, A0A1P7Y0A8, A0A1P7Y0C9, A0A1P7Y0D0, A0A1P7Y0D4, A0A1Y1C7Q5, A0A2Z6AQX7, A0A345BJQ0, A0A348DU52, A0A386JV86, A0A3G1DJL2, A0A6S6QR11, A0A8H4CUY8, A0SJQ5, C9E894, D0VFU8, D2K762, G0Y286, G0Y287, G0Y288, O48666, O65688, O74165, P29704, P36596, P37268, P53798, P53799, P53800, P78589, P9WEP0, P9WEV2, P9WEV7, Q02769, Q0CRW6

Diamond homologs: A0A142ZC57, A0A144YEA5, A0A1D8PI71, A0A1P7Y0A2, A0A1P7Y0A8, A0A1P7Y0C9, A0A1P7Y0D0, A0A1P7Y0D4, A0A345BJQ0, A0A3G1DJL2, A0SJQ5, C9E894, D0VFU8, D2K762, G0Y286, G0Y287, G0Y288, O48666, O65688, O74165, P29704, P36596, P37268, P53798, P53799, P53800, P78589, Q02769, Q32KR6, Q4WAG4, Q54DR1, Q5R6U3, Q752X9, Q7S4Z6, Q92459, Q9HGZ6, Q9SDW9, Q9Y753, V6RPN0, P37269

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	5
Uncertain significance	105
Likely benign	26
Benign	15

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
152005	GRCh38/hg38 8p23.1(chr8:11739235-11803434)x1	Pathogenic
442916	GRCh37/hg19 8p23.1(chr8:11608214-11683083)x1	Pathogenic
587360	NC_000008.10:g.11667760_11787743del	Pathogenic
587361	NM_004462.5(FDFT1):c.880-24_880-23delinsAG	Likely pathogenic
587362	NC_000008.11:g.11802586_11802601del	Likely pathogenic
599353	NC_000008.10:g.11667760_11787743del119984	Likely pathogenic
635939	Single allele	Likely pathogenic
996898	NM_004462.5(FDFT1):c.899T>A (p.Leu300Ter)	Likely pathogenic

SpliceAI

1535 predictions. Top by Δscore:

Variant	Effect	Δscore
8:11808889:GCG:G	donor_gain	1.0000
8:11809663:A:AG	acceptor_gain	1.0000
8:11809664:C:G	acceptor_gain	1.0000
8:11809665:A:AG	acceptor_gain	1.0000
8:11809666:G:GG	acceptor_gain	1.0000
8:11809666:GC:G	acceptor_gain	1.0000
8:11809666:GCA:G	acceptor_gain	1.0000
8:11809666:GCAA:G	acceptor_gain	1.0000
8:11809666:GCAAC:G	acceptor_gain	1.0000
8:11809848:ACGGT:A	donor_loss	1.0000
8:11809849:CGGTG:C	donor_loss	1.0000
8:11809850:GGT:G	donor_loss	1.0000
8:11809851:G:GG	donor_gain	1.0000
8:11821874:ACAAG:A	donor_loss	1.0000
8:11821875:CAAGG:C	donor_loss	1.0000
8:11821876:AAGG:A	donor_loss	1.0000
8:11821877:AGGTT:A	donor_loss	1.0000
8:11821878:GGTT:G	donor_loss	1.0000
8:11821879:G:GC	donor_loss	1.0000
8:11821880:T:G	donor_loss	1.0000
8:11826022:A:AG	acceptor_gain	1.0000
8:11826023:G:GG	acceptor_gain	1.0000
8:11826213:GAG:G	donor_gain	1.0000
8:11826215:GG:G	donor_loss	1.0000
8:11826216:GTA:G	donor_loss	1.0000
8:11826217:T:G	donor_loss	1.0000
8:11831506:T:TA	acceptor_gain	1.0000
8:11831509:T:A	acceptor_gain	1.0000
8:11831515:TAG:T	acceptor_loss	1.0000
8:11831516:A:AG	acceptor_gain	1.0000

AlphaMissense

2773 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:11830403:T:C	F288L	0.997
8:11830405:C:A	F288L	0.997
8:11830405:C:G	F288L	0.997
8:11808854:T:C	F54L	0.996
8:11808856:C:A	F54L	0.996
8:11808856:C:G	F54L	0.996
8:11826051:G:A	G180R	0.996
8:11826051:G:C	G180R	0.996
8:11826058:G:A	G182D	0.996
8:11826052:G:A	G180E	0.995
8:11826057:G:C	G182R	0.995
8:11830410:C:A	A290D	0.995
8:11809699:G:C	R77P	0.993
8:11826070:T:C	L186P	0.993
8:11830409:G:C	A290P	0.993
8:11831524:G:C	A296P	0.993
8:11831609:T:C	L324P	0.993
8:11808846:G:T	S51I	0.992
8:11808876:T:C	L61P	0.992
8:11826061:T:C	L183P	0.992
8:11826204:T:A	W231R	0.992
8:11826204:T:C	W231R	0.992
8:11809709:C:A	D80E	0.991
8:11809709:C:G	D80E	0.991
8:11826061:T:A	L183H	0.991
8:11808823:C:G	C43W	0.990
8:11821809:C:G	C147W	0.990
8:11808845:A:C	S51R	0.989
8:11808847:T:A	S51R	0.989
8:11808847:T:G	S51R	0.989

dbSNP variants (sampled 300 via entrez): RS1000053648 (8:11816529 C>T), RS1000054229 (8:11826495 C>A,G), RS1000069977 (8:11821535 G>T), RS1000073785 (8:11812216 C>A,G), RS1000082458 (8:11809095 C>A,G,T), RS1000098745 (8:11805944 C>T), RS1000125787 (8:11817685 T>A,C,G), RS1000148687 (8:11801319 G>C), RS1000176790 (8:11809201 A>G), RS1000210513 (8:11827661 C>A,G), RS1000234493 (8:11824728 T>G), RS1000267964 (8:11796672 G>A,C), RS1000295935 (8:11833152 T>C), RS1000309461 (8:11794879 T>C), RS1000322236 (8:11831661 T>C)

Disease associations

OMIM: gene MIM:184420 | disease phenotypes: MIM:618156

GenCC curated gene-disease

Disease	Classification	Inheritance
squalene synthase deficiency	Strong	Autosomal recessive
retinitis pigmentosa	Limited	Autosomal recessive

Mondo (3): squalene synthase deficiency (MONDO:0032566), neurodevelopmental disorder (MONDO:0700092), retinitis pigmentosa (MONDO:0019200)

Orphanet (0):

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000047	Hypospadias
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000609	Optic nerve hypoplasia
HP:0000737	Irritability
HP:0000958	Dry skin
HP:0000992	Cutaneous photosensitivity
HP:0001250	Seizure
HP:0001511	Intrauterine growth retardation
HP:0001531	Failure to thrive in infancy
HP:0001647	Bicuspid aortic valve
HP:0002019	Constipation
HP:0002079	Hypoplasia of the corpus callosum
HP:0002126	Polymicrogyria
HP:0002987	Elbow flexion contracture
HP:0003100	Slender long bone
HP:0003146	Hypocholesterolemia
HP:0003563	Decreased LDL cholesterol concentration
HP:0004691	2-3 toe syndactyly
HP:0005280	Depressed nasal bridge
HP:0006380	Knee flexion contracture
HP:0008689	Bilateral cryptorchidism
HP:0009887	Abnormality of hair pigmentation
HP:0011471	Gastrostomy tube feeding in infancy
HP:0012736	Profound global developmental delay

GWAS associations

46 associations (top):

Study	Trait	p-value
GCST000765_15	Non-alcoholic fatty liver disease histology (other)	7.000000e-07
GCST000766_3	Non-alcoholic fatty liver disease histology (lobular)	3.000000e-06
GCST002281_13	Ejection fraction in Tripanosoma cruzi seropositivity	4.000000e-07
GCST002579_19	Heschl’s gyrus morphology	6.000000e-06
GCST005273_3	Polycystic ovary syndrome	8.000000e-10
GCST007615_27	C-reactive protein levels	3.000000e-13
GCST007615_69	C-reactive protein levels	7.000000e-15
GCST007709_221	General factor of neuroticism	1.000000e-08
GCST007709_248	General factor of neuroticism	4.000000e-09
GCST009391_2	Metabolite levels	9.000000e-06
GCST010002_269	Refractive error	1.000000e-24
GCST010132_11	Processed meat consumption	4.000000e-10
GCST010132_14	Processed meat consumption	2.000000e-15
GCST010132_15	Processed meat consumption	1.000000e-09
GCST010142_4	Fish- and plant-related diet	2.000000e-12
GCST010142_6	Fish- and plant-related diet	3.000000e-12
GCST010142_89	Fish- and plant-related diet	4.000000e-16
GCST010142_90	Fish- and plant-related diet	7.000000e-15
GCST010703_306	Brain morphology (MOSTest)	5.000000e-26
GCST012226_743	Waist circumference adjusted for body mass index	5.000000e-10
GCST012226_744	Waist circumference adjusted for body mass index	2.000000e-14
GCST012226_790	Waist circumference adjusted for body mass index	3.000000e-12
GCST012226_791	Waist circumference adjusted for body mass index	7.000000e-10
GCST012226_792	Waist circumference adjusted for body mass index	4.000000e-09
GCST012228_416	Waist-hip index	5.000000e-11
GCST012228_417	Waist-hip index	1.000000e-10
GCST012228_418	Waist-hip index	4.000000e-10
GCST012228_420	Waist-hip index	4.000000e-14
GCST012230_100	Waist-to-hip ratio adjusted for BMI	3.000000e-10
GCST012230_51	Waist-to-hip ratio adjusted for BMI	1.000000e-09

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0005527	ejection fraction measurement
EFO:0004458	C-reactive protein measurement
EFO:0007660	neuroticism measurement
EFO:0009777	citrulline measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007986	reticulocyte count
EFO:0010701	mean reticulocyte volume
EFO:0004309	platelet count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3338 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 30,887 (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
CHEMBL633	AMIODARONE	4	29,704
CHEMBL435224	LAPAQUISTAT ACETATE	3	959
CHEMBL561057	SQ109	2	224

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Lanosterol biosynthesis pathway

Most potent curated ligand interactions (81 total), top 25:

Ligand	Action	Affinity	Parameter
compound 21 [PMID: 7473541]	Inhibition	11.4	pIC50
zaragozic acid B	Inhibition	10.5	pKi
zaragozic acid C	Inhibition	10.4	pKi
compound 5d [PMID: 7966163]	Inhibition	10.4	pIC50
compound 19 [PMID: 7473541]	Inhibition	10.3	pIC50
compound 6g [PMID: 7966163]	Inhibition	10.22	pIC50
compound 4e [PMID: 7966163]	Inhibition	10.15	pIC50
compound 6d [PMID: 7966163]	Inhibition	10.05	pIC50
compound 6c [PMID: 7966163]	Inhibition	9.92	pIC50
compound 3f [PMID: 7966163]	Inhibition	9.89	pIC50
L-735021	Inhibition	9.85	pIC50
compound 28 [PMID: 7473541]	Inhibition	9.7	pIC50
compound 20 [PMID: 7473541]	Inhibition	9.22	pIC50
zaragozic acid A	Inhibition	9.15	pIC50
J-104118	Inhibition	9.14	pIC50
compound 6 [PMID: 7629799]	Inhibition	9.0	pIC50
SQ-34919	Inhibition	9.0	pIC50
compound 15a [PMID: 22464687]	Inhibition	8.9	pIC50
E5700	Inhibition	8.82	pIC50
compound 1e [Brown et al., 1997]	Inhibition	8.7	pKi
compound 32 [PMID: 19191557]	Inhibition	8.7	pIC50
compound 2e [PMID: 7629799]	Inhibition	8.6	pIC50
J-104123	Inhibition	8.6	pIC50
compound 2d [PMID: 7629799]	Inhibition	8.59	pIC50

ChEMBL bioactivities

194 potent at pChembl≥5 of 204 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.2	nM	CHEMBL507677
9.62	IC50	0.24	nM	ZARAGOZIC ACID A
9.55	IC50	0.28	nM	CHEMBL335394
9.52	IC50	0.3	nM	ZARAGOZIC ACID C
9.52	IC50	0.3	nM	CHEMBL436588
9.35	IC50	0.45	nM	CHEMBL1684849
9.28	IC50	0.52	nM	CHEMBL61985
9.19	IC50	0.64	nM	CHEMBL441322
9.14	IC50	0.73	nM	CHEMBL2115091
9.07	IC50	0.85	nM	CHEMBL1684826
9.02	IC50	0.96	nM	CHEMBL132100
9.00	IC50	1	nM	CHEMBL460895
8.96	IC50	1.1	nM	CHEMBL1684838
8.96	IC50	1.1	nM	CHEMBL1684996
8.96	IC50	1.1	nM	CHEMBL1684999
8.92	IC50	1.2	nM	CHEMBL61935
8.89	IC50	1.3	nM	CHEMBL1684829
8.89	IC50	1.3	nM	CHEMBL1685008
8.89	IC50	1.3	nM	CHEMBL1685025
8.82	IC50	1.5	nM	CHEMBL258717
8.80	IC50	1.6	nM	CHEMBL1684833
8.77	IC50	1.7	nM	CHEMBL1685014
8.70	IC50	2	nM	CHEMBL88601
8.70	IC50	2	nM	ZARAGOZIC ACID F
8.70	IC50	2	nM	CHEMBL490300
8.70	IC50	2	nM	CHEMBL1684994
8.70	IC50	2	nM	CHEMBL1685028
8.64	IC50	2.3	nM	CHEMBL1684837
8.62	IC50	2.4	nM	CHEMBL1684831
8.60	IC50	2.5	nM	CHEMBL143820
8.59	IC50	2.6	nM	CHEMBL1685005
8.55	IC50	2.8	nM	CHEMBL1685017
8.52	IC50	3	nM	CHEMBL160318
8.52	IC50	3	nM	CHEMBL460896
8.49	IC50	3.2	nM	CHEMBL59729
8.49	IC50	3.2	nM	CHEMBL337655
8.43	IC50	3.7	nM	CHEMBL1684832
8.41	IC50	3.9	nM	CHEMBL356514
8.40	IC50	4	nM	CHEMBL330577
8.40	IC50	4	nM	ZARAGOZIC ACID E
8.40	IC50	4	nM	CHEMBL490890
8.30	IC50	5	nM	ZARAGOZIC ACIDS A
8.30	IC50	5	nM	CHEMBL515716
8.30	IC50	5	nM	CHEMBL302601
8.30	IC50	5	nM	CHEMBL86319
8.22	IC50	6	nM	CHEMBL258503
8.17	IC50	6.8	nM	CHEMBL1685029
8.15	IC50	7	nM	CHEMBL315074
8.15	IC50	7	nM	CHEMBL1685018
8.15	IC50	7	nM	CHEMBL265765

PubChem BioAssay actives

159 with measured affinity, of 308 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
(6R,7R)-1-[(4S,5R)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecoxycarbonyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid	204999: compound required to inhibit 50% activity of yeast squalene synthase enzyme (YESS)	ic50	0.0003	uM
(6R,7R)-1-[(4S,5R)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-dodecoxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid	204999: compound required to inhibit 50% activity of yeast squalene synthase enzyme (YESS)	ic50	0.0003	uM
ethyl 1-[4-[4-chloro-N-(2,2-dimethylpropyl)-2-[(2-fluorophenyl)-hydroxymethyl]anilino]-4-oxobutanoyl]piperidine-4-carboxylate	578752: Inhibition of squalene synthase	ic50	0.0004	uM
(6R,7R)-1-[(4S,5R)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-decoxycarbonyloxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid	204999: compound required to inhibit 50% activity of yeast squalene synthase enzyme (YESS)	ic50	0.0006	uM
ethyl 1-[4-[4-chloro-2-[(2-chlorophenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperidine-4-carboxylate	578752: Inhibition of squalene synthase	ic50	0.0008	uM
tetrapotassium;dioxido-oxo-[4-(4-phenylphenyl)-1-phosphonatobutyl]-lambda5-phosphane	346343: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation	ic50	0.0010	uM
(6R,7R)-1-[(4S,5R)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-dodecanoyloxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid	204998: Compound required to inhibit 50% activity of yeast squalene synthase enzyme (YESS)	ic50	0.0010	uM
ethyl 1-[4-[4-chloro-N-(2,2-dimethylpropyl)-2-[hydroxy-(2-methoxyphenyl)methyl]anilino]-4-oxobutanoyl]piperidine-4-carboxylate	578752: Inhibition of squalene synthase	ic50	0.0011	uM
benzyl 4-[4-[4-chloro-2-[(2-chlorophenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperazine-1-carboxylate	578752: Inhibition of squalene synthase	ic50	0.0011	uM
ethyl 1-[4-[4-chloro-2-[(2,3-dimethoxyphenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperidine-4-carboxylate	578752: Inhibition of squalene synthase	ic50	0.0011	uM
1-[4-[4-chloro-N-(2,2-dimethylpropyl)-2-[hydroxy-(2-methoxyphenyl)methyl]anilino]-4-oxobutanoyl]piperidine-3-carboxylic acid	578752: Inhibition of squalene synthase	ic50	0.0013	uM
ethyl 1-[4-[4-chloro-2-[(2,3-dimethoxyphenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperidine-3-carboxylate	578752: Inhibition of squalene synthase	ic50	0.0013	uM
1-[4-[4-chloro-2-[(2-chlorophenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]-N-methylpiperidine-4-carboxamide	578752: Inhibition of squalene synthase	ic50	0.0013	uM
(3R)-3-[2-[2-benzyl-6-[(3R,4S)-3-hydroxy-4-methoxypyrrolidin-1-yl]-3-pyridinyl]ethynyl]-1-azabicyclo[2.2.2]octan-3-ol	326566: Inhibition of human recombinant squalene synthase	ic50	0.0015	uM
N-butyl-1-[4-[4-chloro-2-[(2-chlorophenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperidine-4-carboxamide	578752: Inhibition of squalene synthase	ic50	0.0016	uM
1-[4-[4-chloro-N-(2,2-dimethylpropyl)-2-[hydroxy-(2-methoxyphenyl)methyl]anilino]-4-oxobutanoyl]piperidine-4-carboxylic acid	578752: Inhibition of squalene synthase	ic50	0.0017	uM
tripotassium;4-[3-(1-benzofuran-5-yloxy)phenyl]-1-phosphonatobutane-1-sulfonate	346343: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation	ic50	0.0020	uM
ethyl 1-[4-[4-chloro-2-[(2-chloro-4-fluorophenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperidine-4-carboxylate	578752: Inhibition of squalene synthase	ic50	0.0020	uM
1-[4-[4-chloro-2-[(2,3-dimethoxyphenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperidine-3-carboxylic acid	578752: Inhibition of squalene synthase	ic50	0.0020	uM
ethyl 4-[4-[4-chloro-2-[(2-chlorophenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperazine-1-carboxylate	578752: Inhibition of squalene synthase	ic50	0.0023	uM
1-[4-[4-chloro-2-[(2-chlorophenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]-N-ethylpiperidine-4-carboxamide	578752: Inhibition of squalene synthase	ic50	0.0024	uM
ethyl 1-[4-[4-chloro-N-(2,2-dimethylpropyl)-2-[hydroxy-(2-methoxyphenyl)methyl]anilino]-4-oxobutanoyl]piperidine-3-carboxylate	578752: Inhibition of squalene synthase	ic50	0.0026	uM
1-[4-[4-chloro-2-[(2,3-dimethoxyphenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperidine-4-carboxylic acid	578752: Inhibition of squalene synthase	ic50	0.0028	uM
tetrapotassium;dioxido-oxo-[1-phosphonato-4-[4-[4-(trifluoromethyl)phenyl]phenyl]butyl]-lambda5-phosphane	346343: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation	ic50	0.0030	uM
tripotassium;4-[3-(2-benzylphenoxy)phenyl]-1-phosphonatobutane-1-sulfonate	346343: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation	ic50	0.0030	uM
(6R,7R)-1-[(4S,5R)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-(decylcarbamoyloxy)-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid	204999: compound required to inhibit 50% activity of yeast squalene synthase enzyme (YESS)	ic50	0.0032	uM
1-[4-[4-chloro-2-[(2-chlorophenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]-N-propan-2-ylpiperidine-4-carboxamide	578752: Inhibition of squalene synthase	ic50	0.0037	uM
tripotassium;4-[2-fluoro-5-(4-fluorophenoxy)phenyl]-1-phosphonatobutane-1-sulfonate	346343: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation	ic50	0.0040	uM
tripotassium;4-[3-(2-fluorophenoxy)phenyl]-1-phosphonatobutane-1-sulfonate	346343: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation	ic50	0.0050	uM
(1S,3S,4S,5R,6R,7R)-1-[(4R,5S)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-[(E,4S,6S)-4,6-dimethyloct-2-enoyl]oxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid	204675: Compound was tested for in vitro inhibitory activity against Candida albicans 2005E microsomal SQS	ic50	0.0050	uM
(3R)-3-[2-[2-benzyl-6-(3-methoxypropoxy)-3-pyridinyl]ethynyl]-1-azabicyclo[2.2.2]octan-3-ol	326566: Inhibition of human recombinant squalene synthase	ic50	0.0060	uM
1-[4-[4-chloro-2-[2,3-dihydro-1,4-benzodioxin-5-yl(hydroxy)methyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperidine-3-carboxylic acid	578752: Inhibition of squalene synthase	ic50	0.0068	uM
(1S,3S,4S,5R,6R,7R)-1-[(4S,5S)-4-acetyloxy-3,5-dimethyl-6-phenylhexyl]-6-[(4R,6S)-4,6-dimethyloctanoyl]oxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid	204675: Compound was tested for in vitro inhibitory activity against Candida albicans 2005E microsomal SQS	ic50	0.0070	uM
1-[4-[4-chloro-2-[2,3-dihydro-1,4-benzodioxin-5-yl(hydroxy)methyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperidine-4-carboxylic acid	578752: Inhibition of squalene synthase	ic50	0.0070	uM
ethyl 1-[4-[4-chloro-2-[(2-chloro-3-fluorophenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperidine-4-carboxylate	578752: Inhibition of squalene synthase	ic50	0.0072	uM
ethyl 2-[4-[4-[4-chloro-2-[(2-chlorophenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperazin-1-yl]acetate	578752: Inhibition of squalene synthase	ic50	0.0079	uM
tripotassium;4-[3-(3-fluorophenoxy)phenyl]-1-phosphonatobutane-1-sulfonate	346343: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation	ic50	0.0080	uM
1-[4-[4-chloro-2-[(2-chloro-3-fluorophenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperidine-3-carboxylic acid	578752: Inhibition of squalene synthase	ic50	0.0084	uM
(1S,3S,4S,5R,6R,7R)-6-[(4R,6S)-4,6-dimethyloctanoyl]oxy-4,7-dihydroxy-1-[(4S,5S)-4-hydroxy-3,5-dimethyl-6-phenylhexyl]-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid	204675: Compound was tested for in vitro inhibitory activity against Candida albicans 2005E microsomal SQS	ic50	0.0090	uM
ethyl 1-[4-[4-chloro-2-[2,3-dihydro-1,4-benzodioxin-5-yl(hydroxy)methyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperidine-4-carboxylate	578752: Inhibition of squalene synthase	ic50	0.0100	uM
ethyl 1-[4-[4-chloro-2-[2,3-dihydro-1,4-benzodioxin-5-yl(hydroxy)methyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperidine-3-carboxylate	578752: Inhibition of squalene synthase	ic50	0.0130	uM
tripotassium;4-[3-(3,4-dichlorophenoxy)phenyl]-1-phosphonatobutane-1-sulfonate	346343: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation	ic50	0.0140	uM
(1S,3S,4S,5R,6R,7R)-6-[(4R,6S)-4,6-dimethyloctanoyl]oxy-1-[(5R)-3,5-dimethyl-6-phenylhexyl]-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid	204675: Compound was tested for in vitro inhibitory activity against Candida albicans 2005E microsomal SQS	ic50	0.0140	uM
3-[[2-[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-5H-4,1-benzoxazepin-3-yl]acetyl]amino]propanoic acid	227678: Inhibition of squalene synthase from human hepatoma cells (HepG2)	ic50	0.0150	uM
2-[[2-[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-5H-4,1-benzoxazepin-3-yl]acetyl]amino]acetic acid	227678: Inhibition of squalene synthase from human hepatoma cells (HepG2)	ic50	0.0150	uM
tripotassium;4-[3-(4-fluorophenoxy)phenyl]-1-phosphonatobutane-1-sulfonate	346343: Inhibition of human recombinant squalene synthase expressed in Escherichia coli BL21 (DE3) cells assessed as formation of 1,10-dioic acid metabolite by liquid scintillation	ic50	0.0170	uM
1-[4-[4-chloro-2-[(2-chloro-3-fluorophenyl)-hydroxymethyl]-N-(2,2-dimethylpropyl)anilino]-4-oxobutanoyl]piperidine-4-carboxylic acid	578752: Inhibition of squalene synthase	ic50	0.0170	uM
(2R)-2-[[2-[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-5H-4,1-benzoxazepin-3-yl]acetyl]amino]propanoic acid	227678: Inhibition of squalene synthase from human hepatoma cells (HepG2)	ic50	0.0180	uM
2-[[2-[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-5H-4,1-benzoxazepin-3-yl]acetyl]-methylamino]acetic acid	227678: Inhibition of squalene synthase from human hepatoma cells (HepG2)	ic50	0.0180	uM
1-[2-[(3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-(3-hydroxy-2,2-dimethylpropyl)-2-oxo-5H-4,1-benzoxazepin-3-yl]acetyl]piperidine-4-carboxylic acid	227678: Inhibition of squalene synthase from human hepatoma cells (HepG2)	ic50	0.0180	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	5
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	5
bisphenol A	decreases expression, increases expression, affects expression	4
Cisplatin	increases expression, decreases expression, increases reaction, affects expression, affects cotreatment	4
perfluorooctanoic acid	decreases expression, increases expression	3
perfluorooctane sulfonic acid	decreases expression	3
Resveratrol	affects cotreatment, increases expression, decreases reaction	3
Cyclosporine	affects cotreatment, affects expression, decreases expression	3
deoxynivalenol	decreases expression	2
methacrylaldehyde	affects cotreatment, affects expression, affects oxidation, decreases expression, increases oxidation (+1 more)	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Acrolein	affects cotreatment, affects expression, affects oxidation, decreases expression, increases oxidation (+1 more)	2
Benzo(a)pyrene	decreases expression	2
Ozone	affects cotreatment, affects expression, affects oxidation, decreases expression, increases oxidation (+1 more)	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Rotenone	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Tretinoin	decreases expression, increases expression	2
Tunicamycin	decreases expression	2
beta-Naphthoflavone	affects reaction, decreases expression	2
Copper Sulfate	decreases expression, increases expression	2
Simvastatin	increases activity, decreases reaction, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
afuresertib	increases expression	1
22-hydroxycholesterol	decreases expression	1
tremortin	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, affects expression, affects oxidation, decreases expression	1

ChEMBL screening assays

40 unique, capped per target: 40 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004403	Binding	Inhibition of squalene synthase	Clavaric acid: a triterpenoid inhibitor of farnesyl-protein transferase from Clavariadelphus truncatus. — J Nat Prod

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1WC	Abcam A-549 FDFT1 KO	Cancer cell line	Male
CVCL_D2AR	Abcam HCT 116 FDFT1 KO	Cancer cell line	Male
CVCL_D2ND	Abcam THP-1 FDFT1 KO	Cancer cell line	Male
CVCL_F1Q6	HyCyte Hep-G2 KO-hFDFT1	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
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,
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
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
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene