SQLE

Summary

SQLE (squalene epoxidase, HGNC:11279) is a protein-coding gene on chromosome 8q24.13, encoding Squalene monooxygenase (Q14534). Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.

Enables FAD binding activity and squalene monooxygenase activity. Involved in lipid droplet formation; regulation of cell population proliferation; and sterol biosynthetic process. Located in intracellular membrane-bounded organelle and membrane.

Source: NCBI Gene 6713 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 75 total — 1 pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003129

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11279
Approved symbol	SQLE
Name	squalene epoxidase
Location	8q24.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000104549
Ensembl biotype	protein_coding
OMIM	602019
Entrez	6713

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 2 retained_intron

ENST00000265896, ENST00000518604, ENST00000518931, ENST00000520493, ENST00000521232, ENST00000523430, ENST00000873973, ENST00000873974, ENST00000939649, ENST00000939650, ENST00000939651

RefSeq mRNA: 1 — MANE Select: NM_003129 NM_003129

CCDS: CCDS47918

Canonical transcript exons

ENST00000265896 — 11 exons

Exon	Start	End
ENSE00000703271	125008971	125009084
ENSE00000703272	125009172	125009343
ENSE00000703274	125011537	125011632
ENSE00000703278	125018631	125018727
ENSE00000871765	125021753	125022283
ENSE00000871767	125005525	125005705
ENSE00000871769	124998505	124999694
ENSE00001028522	125003176	125003428
ENSE00001089200	125018059	125018201
ENSE00001089205	125020784	125020871
ENSE00001089208	125007391	125007487

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.2461 / max 579.9814, expressed in 1815 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
90526	28.7188	1802
90527	10.3118	1703
90529	0.4433	173
90537	0.4194	204
90531	0.2929	114
90530	0.2890	131
90528	0.2179	111
90533	0.1555	33
90534	0.1500	25
90535	0.1411	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.23	gold quality
ventricular zone	UBERON:0003053	98.94	gold quality
ganglionic eminence	UBERON:0004023	98.62	gold quality
embryo	UBERON:0000922	98.38	gold quality
cortical plate	UBERON:0005343	98.18	gold quality
gingival epithelium	UBERON:0001949	97.67	gold quality
esophagus squamous epithelium	UBERON:0006920	97.39	gold quality
bronchial epithelial cell	CL:0002328	97.35	gold quality
gingiva	UBERON:0001828	97.21	gold quality
cartilage tissue	UBERON:0002418	96.63	gold quality
squamous epithelium	UBERON:0006914	96.61	gold quality
epithelium of bronchus	UBERON:0002031	96.55	gold quality
nipple	UBERON:0002030	96.36	gold quality
bronchus	UBERON:0002185	96.34	gold quality
epithelium of esophagus	UBERON:0001976	96.21	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.06	gold quality
esophagus mucosa	UBERON:0002469	96.01	gold quality
spinal cord	UBERON:0002240	95.65	gold quality
inferior vagus X ganglion	UBERON:0005363	95.43	gold quality
tibia	UBERON:0000979	95.22	gold quality
penis	UBERON:0000989	95.13	gold quality
corpus callosum	UBERON:0002336	94.89	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.75	gold quality
cranial nerve II	UBERON:0000941	94.68	gold quality
superior vestibular nucleus	UBERON:0007227	94.49	gold quality
skin of abdomen	UBERON:0001416	94.41	gold quality
islet of Langerhans	UBERON:0000006	94.37	gold quality
pons	UBERON:0000988	94.27	gold quality
skin of leg	UBERON:0001511	94.02	gold quality
zone of skin	UBERON:0000014	93.80	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	645.88
E-MTAB-8142	yes	67.43
E-MTAB-4850	no	813.84
E-MTAB-8205	no	436.65
E-MTAB-10290	no	321.13
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, NFYA, SREBF1, SREBF2

miRNA regulators (miRDB)

34 targeting SQLE, 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-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-133A-3P	99.27	71.53	1270
HSA-MIR-133B	99.27	71.53	1270
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-6881-3P	98.04	68.24	1777

Literature-anchored findings (GeneRIF, showing 40)

• functional promotor regions involved in transcription was determined (PMID:12083769)
• A cDNA library consisting of 220 upregulated genes in tumour tissue was established and named as LSCC. Differential expression was confirmed in five of these genes, including IGFBP5, SQLE, RAP2B, CLDN1, and TBL1XR1. (PMID:17316888)
• Distant metastasis-free survival in stage I/II breast cancer cases was significantly inversely related to SQLE mRNA in multivariate Cox analysis in two independent patient cohorts of 160 patients each (PMID:18728668)
• MARCH6 and squalene monooxygenase (SM) physically interact, and consistent with MARCH6 acting as an E3 ligase, its overexpression reduces SM abundance in a RING-dependent manner. (PMID:24449766)
• Data suggest that unsaturated fatty acids (oleate; oleoyl-CoA) stabilize SM/SQLE (which catalyzes 1st oxygenation step in cholesterol synthesis) most likely via inhibition of poly-ubiquitination by MARCH6 (membrane-associated ring finger [C3HC4] 6). (PMID:24840124)
• overexpression of SQLE in HCC cells promoted cell proliferation and migration, while downregulation of SQLE inhibited the tumorigenicity of Hepatocellular carcinoma cells in vitro and in vivo. (PMID:25787749)
• this study have identified a Squalene Monooxygenase region integrally associated with the endoplasmic reticulum membrane that is likely to interact with cholesterol or respond to cholesterol-induced membrane effects. (PMID:26434806)
• our results pinpoint SQLE as a bona fide metabolic oncogene by amplification, and as a therapeutic target in BC. These findings could have implications in other cancer types. (PMID:26777065)
• Data indicate that microRNA miR-133b-dependent squalene epoxidase (SQLE) plays a critical role in the potential metastasis mechanisms in esophageal squamous cell carcinoma (ESCC). (PMID:28069586)
• Both HMGCR and SQLE promoters have two SREs that may act as a homing region to attract a single SREBP-2 homodimer. (PMID:28342963)
• Higher Gleason grade was associated with lower LDLR expression, lower SOAT1 and higher SQLE expression. Besides high SQLE expression, cancers that became lethal despite primary treatment were characterized by low LDLR expression (odds ratio for highest versus lowest quintile, 0.37; 95% CI 0.18-0.76) and by low SOAT1 expression (odds ratio, 0.41; 95% CI 0.21-0.83). (PMID:28595267)
• Taken together, our results support a model whereby the amphipathic helix in squalene monooxygenase N100 attaches reversibly to the ER membrane depending on cholesterol levels; with excess, the helix is ejected and unravels, exposing a hydrophobic patch, which then serves as a degradation signal. (PMID:28972164)
• Increasingly growing evidence underlines the positive correlation between SE over-expression and poor prognosis in different malignances. SE promotes tumor cell proliferation and migration via many pathways suggesting its oncogenic role. [review] (PMID:29596888)
• Further survival analysis indicated that high expression of SQLE indicated poor prognosis in lung squamous cell carcinoma. Our study presents novel evidence of potential biomarkers or therapeutic targets for lung SCC therapy and prognosis. (PMID:30734525)
• The shape of squalene epoxidase expands the arsenal against cancer. Review. (PMID:30792392)
• findings reveal the degron architecture of SM N100, introducing the role of non-canonical ubiquitination sites and deepening our molecular understanding of how SM is degraded in response to cholesterol. (PMID:30940729)
• OSBPL2 deficiency upregulates SQLE expression and increases the accumulation of cholesterol and cholesteryl ester by suppressing AMPK signalling, which provides new evidence of the connection between OSBPL2 and cholesterol synthesis. (PMID:31356817)
• VCP plays a key role in ERAD that contributes to the cholesterol-mediated regulation of Squalene monooxygenase. (PMID:31471528)
• squalene directly bound to the N100 region, thereby reducing interaction with and ubiquitination by MARCH6 (PMID:32170014)
• The MARCH6-SQLE Axis Controls Endothelial Cholesterol Homeostasis and Angiogenic Sprouting. (PMID:32755570)
• Reduction of Squalene Epoxidase by Cholesterol Accumulation Accelerates Colorectal Cancer Progression and Metastasis. (PMID:32946903)
• The mammalian cholesterol synthesis enzyme squalene monooxygenase is proteasomally truncated to a constitutively active form. (PMID:33933449)
• Squalene epoxidase promotes colorectal cancer cell proliferation through accumulating calcitriol and activating CYP24A1-mediated MAPK signaling. (PMID:34268906)
• MiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer. (PMID:34417456)
• Ferroptosis regulators, especially SQLE, play an important role in prognosis, progression and immune environment of breast cancer. (PMID:34715817)
• Squalene synthase predicts poor prognosis in stage I-III colon adenocarcinoma and synergizes squalene epoxidase to promote tumor progression. (PMID:34939274)
• SQLE facilitates the pancreatic cancer progression via the lncRNA-TTN-AS1/miR-133b/SQLE axis. (PMID:35638462)
• SQLE, A Key Enzyme in Cholesterol Metabolism, Correlates With Tumor Immune Infiltration and Immunotherapy Outcome of Pancreatic Adenocarcinoma. (PMID:35720314)
• Downregulated ferroptosis-related gene SQLE facilitates temozolomide chemoresistance, and invasion and affects immune regulation in glioblastoma. (PMID:35962621)
• Squalene epoxidase promotes hepatocellular carcinoma development by activating STRAP transcription and TGF-beta/SMAD signalling. (PMID:36581319)
• Squalene epoxidase facilitates cervical cancer progression by modulating tumor protein p53 signaling pathway. (PMID:36843235)
• Report of terbinafine resistant Trichophyton spp. in Italy: Clinical presentations, molecular identification, antifungal susceptibility testing and mutations in the squalene epoxidase gene. (PMID:37139949)
• Detection of Squalene Epoxidase Mutations in United States Patients with Onychomycosis: Implications for Management. (PMID:37236595)
• SQLE promotes pancreatic cancer growth by attenuating ER stress and activating lipid rafts-regulated Src/PI3K/Akt signaling pathway. (PMID:37542052)
• Squalene epoxidase promotes breast cancer progression by regulating CCNB1 protein stability. (PMID:37839786)
• Knockdown of SQLE promotes CD8+ T cell infiltration in the tumor microenvironment. (PMID:37993027)
• The expression of squalene epoxidase in human gastric cancer and its clinical significance. (PMID:38084535)
• Squalene monooxygenase facilitates bladder cancer development in part by regulating PCNA. (PMID:38280406)
• Identifying squalene epoxidase as a metabolic vulnerability in high-risk osteosarcoma using an artificial intelligence-derived prognostic index. (PMID:38372422)
• Age-related cholesterol and colorectal cancer progression: Validating squalene epoxidase for high-risk cases. (PMID:38517197)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sqleb	ENSDARG00000063319
danio_rerio	sqlea	ENSDARG00000079946
mus_musculus	Sqle	ENSMUSG00000022351
rattus_norvegicus	Sqle	ENSRNOG00000009550

Protein

Protein identifiers

Squalene monooxygenase — Q14534 (reviewed: Q14534)

Alternative names: Squalene epoxidase

All UniProt accessions (4): E5RJH9, E7EVQ6, Q14534, H0YBN7

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.

Subunit / interactions. Interacts (via N-terminal domain) with MARCHF6. Interacts with SMIM22; this interaction modulates lipid droplet formation.

Subcellular location. Microsome membrane. Endoplasmic reticulum membrane.

Tissue specificity. Detected in liver (at protein level).

Post-translational modifications. Ubiquitinated by MARCHF6 in response to high cholesterol levels in intracellular membranes, leading to proteasomal degradation.

Activity regulation. Inhibited by NB-598 ((E)N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[(3,3’-bi-thiophen-5-yl)methoxy]benzene-methanamine). Contrary to fungal enzymes, the mammalian enzyme is only slightly inhibited by terbinafine. Inhibited by tellurite, tellurium dioxide, selenite, and selenium dioxide.

Domain organisation. The C-terminal hydrophobic region contains two helices that mediate interaction with membranes. Contrary to predictions, this region does not contain transmembrane helices. The N-terminal region mediates interaction with MARCHF6, leading to SQLE ubiquitination and proteasomal degradation when cholosterol levels are high. The first part of the N-terminal region contains a hydrophobic region that inserts into the membrane; contrary to predictions, there are no transmembrane helices. The second part contains a region that can form an amphipathic region that associates with membranes. This region is ejected from the membrane by high cholesterol levels and becomes disordered in an aqueous environment. This is critical for cholesterol-dependent proteasomal degradation. Additional parts of the N-terminal region are predicted to be disordered and contribute to flagging the protein for proteasomal degradation already under basal conditions.

Pathway. Terpene metabolism; lanosterol biosynthesis; lanosterol from farnesyl diphosphate: step 2/3.

Similarity. Belongs to the squalene monooxygenase family.

RefSeq proteins (1): NP_003120* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013698	Squalene_epoxidase	Domain
IPR036188	FAD/NAD-bd_sf	Homologous_superfamily
IPR040125	Squalene_monox	Family

Pfam: PF08491, PF13450

Enzyme classification (BRENDA):

• EC 1.14.14.17 — squalene monooxygenase (BRENDA: 31 organisms, 40 substrates, 145 inhibitors, 18 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SQUALENE	0.0036–7.7	11
FAD	0.0004–0.3	3
(3S)-SQUALENE-2,3-EPOXIDE	0.0043	1
1-CARBA-1-DEAZA-FAD	0.0008	1
O2	0.0043	1
REDUCED NADPH-CYTOCHROME P450 REDUCTASE	—	1

Catalyzed reactions (Rhea), 1 shown:

• squalene + reduced [NADPH–hemoprotein reductase] + O2 = (S)-2,3-epoxysqualene + oxidized [NADPH–hemoprotein reductase] + H2O + H(+) (RHEA:25282)

UniProt features (74 total): helix 20, strand 17, sequence conflict 12, binding site 8, mutagenesis site 6, region of interest 4, topological domain 2, turn 2, chain 1, site 1, intramembrane region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6C6N	X-RAY DIFFRACTION	2.3
6C6P	X-RAY DIFFRACTION	2.5
6C6R	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14534-F1	85.78	0.77

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 (1): 195 (important for enzyme activity)

Ligand- & substrate-binding residues (8): 161; 166; 234; 250; 408; 421; 133–134; 153–154

Mutagenesis-validated functional residues (6):

Position	Phenotype
35	increased expression levels and decreased degradation in response to high membrane cholesterol levels; when associated w
37	increased expression levels and decreased degradation in response to high membrane cholesterol levels; when associated w
62–73	abolishes degradation in response to high membrane cholesterol levels.
65	increased expression levels and decreased degradation in response to high membrane cholesterol levels; when associated w
69	increased expression levels and decreased degradation in response to high membrane cholesterol levels; when associated w
195	loss of enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 326 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, MYAATNNNNNNNGGC_UNKNOWN, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, HORIUCHI_WTAP_TARGETS_DN, JI_RESPONSE_TO_FSH_UP, TSENG_IRS1_TARGETS_UP, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GCANCTGNY_MYOD_Q6, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, GOLDRATH_ANTIGEN_RESPONSE, PATIL_LIVER_CANCER, PUJANA_CHEK2_PCC_NETWORK, SENESE_HDAC1_AND_HDAC2_TARGETS_DN

GO Biological Process (8): cholesterol biosynthetic process (GO:0006695), sterol biosynthetic process (GO:0016126), regulation of cell population proliferation (GO:0042127), lipid droplet formation (GO:0140042), response to biphenyl (GO:1904614), lipid metabolic process (GO:0006629), cholesterol metabolic process (GO:0008203), sterol metabolic process (GO:0016125)

GO Molecular Function (5): squalene monooxygenase activity (GO:0004506), FAD binding (GO:0071949), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), flavin adenine dinucleotide binding (GO:0050660)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), intracellular membrane-bounded organelle (GO:0043231)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
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
sterol metabolic process	2
cholesterol metabolic process	1
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
steroid biosynthetic process	1
cell population proliferation	1
regulation of cellular process	1
lipid storage	1
lipid droplet organization	1
membraneless organelle assembly	1
response to chemical	1
primary metabolic process	1
secondary alcohol metabolic process	1
steroid metabolic process	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen	1
flavin adenine dinucleotide binding	1
binding	1
catalytic activity	1
nucleotide binding	1
anion binding	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
intracellular anatomical structure	1
membrane-bounded organelle	1
intracellular organelle	1

Protein interactions and networks

STRING

3723 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SQLE	FDFT1	P37268	939
SQLE	CYP51A1	Q16850	908
SQLE	FDPS	P14324	893
SQLE	HMGCS1	Q01581	889
SQLE	HMGCR	P04035	864
SQLE	NSDHL	Q15738	856
SQLE	IDI1	Q13907	842
SQLE	LSS	P48449	841
SQLE	MSMO1	Q15800	837
SQLE	TM7SF2	O76062	830
SQLE	DHCR7	Q9UBM7	829
SQLE	SMIM22	K7EJ46	816
SQLE	MVD	P53602	816
SQLE	SC5D	O75845	811
SQLE	DHCR24	Q15392	810

IntAct

76 interactions, top by confidence:

A	B	Type	Score
FAF2	UBB	psi-mi:“MI:0914”(association)	0.640
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
SQLE	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
SQLE	REEP4	psi-mi:“MI:0915”(physical association)	0.560
SQLE	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
TREML2	SNX2	psi-mi:“MI:0914”(association)	0.530
SLC30A2	RER1	psi-mi:“MI:0914”(association)	0.530
CHRND	TPST2	psi-mi:“MI:0914”(association)	0.530
KCNA2	FADS1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
SQLE	MARCHF6	psi-mi:“MI:0915”(physical association)	0.400
ALDOC	SQLE	psi-mi:“MI:0915”(physical association)	0.370
SQLE	ZNF641	psi-mi:“MI:0915”(physical association)	0.370
CREB3	SQLE	psi-mi:“MI:0915”(physical association)	0.370
TMCO3	POTEF	psi-mi:“MI:0914”(association)	0.350
SLC39A12	POM121C	psi-mi:“MI:0914”(association)	0.350
ATP2B2	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC18A1	LIMK2	psi-mi:“MI:0914”(association)	0.350
SLC17A2	PSMD11	psi-mi:“MI:0914”(association)	0.350
PCDHGA5	MAP2K7	psi-mi:“MI:0914”(association)	0.350
CHRND	EXTL3	psi-mi:“MI:0914”(association)	0.350
HLA-DRB1	CTDNEP1	psi-mi:“MI:0914”(association)	0.350
	LRPPRC	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
SMIM22	SPINT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (75): SQLE (Affinity Capture-Western), SQLE (Affinity Capture-MS), SQLE (Affinity Capture-MS), SQLE (Affinity Capture-MS), SQLE (Affinity Capture-MS), SQLE (Affinity Capture-MS), SQLE (Affinity Capture-MS), SQLE (Affinity Capture-MS), SQLE (Affinity Capture-MS), SQLE (Affinity Capture-MS), SQLE (Affinity Capture-MS), SQLE (Affinity Capture-MS), SQLE (Affinity Capture-MS), SQLE (Affinity Capture-MS), SQLE (Affinity Capture-MS)

ESM2 similar proteins: A0A0K9RDW0, B9DFG3, C3VEQ2, F4J117, F4KHG6, K4C9E2, O23052, O24163, O49901, O49931, O81360, O82290, P52019, P52020, P93236, Q0DVX2, Q0JCU7, Q14534, Q2VEX9, Q38933, Q40412, Q40424, Q42435, Q43415, Q43503, Q43578, Q56X76, Q5N800, Q6DYE4, Q6ZHJ5, Q84JF5, Q84W55, Q84W56, Q8GXR9, Q93ZA0, Q944I4, Q96375, Q9C664, Q9FGC7, Q9FIG9

Diamond homologs: B7TWW5, E9R5G2, I1RQ76, O13306, O48651, O65402, O65403, O65404, O65726, O65727, O81000, P32476, P52019, P52020, P53572, Q14534, Q4KCZ0, Q75F69, Q8VYH2, Q92206, Q9C1W3, Q9SM02, A0QRI8, Q3S8R0, P9WNY8, P9WNY9, Q7Q6A7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SREBF2	“up-regulates quantity by expression”	SQLE	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	53
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4070986	NM_003129.4(SQLE):c.1278del (p.Asp427fs)	Pathogenic

SpliceAI

1765 predictions. Top by Δscore:

Variant	Effect	Δscore
8:125003174:A:AG	acceptor_gain	1.0000
8:125003175:G:GG	acceptor_gain	1.0000
8:125003175:GC:G	acceptor_gain	1.0000
8:125003175:GCGCA:G	acceptor_gain	1.0000
8:125005511:C:A	acceptor_gain	1.0000
8:125005515:T:A	acceptor_gain	1.0000
8:125005523:A:AG	acceptor_gain	1.0000
8:125005524:G:GA	acceptor_gain	1.0000
8:125005524:GA:G	acceptor_gain	1.0000
8:125005524:GAT:G	acceptor_gain	1.0000
8:125005524:GATA:G	acceptor_gain	1.0000
8:125005701:CCCAA:C	donor_gain	1.0000
8:125005702:CCAAG:C	donor_loss	1.0000
8:125005704:AAGT:A	donor_loss	1.0000
8:125005705:AG:A	donor_loss	1.0000
8:125005706:G:GG	donor_gain	1.0000
8:125005707:T:G	donor_loss	1.0000
8:125007389:A:AG	acceptor_gain	1.0000
8:125007390:G:GG	acceptor_gain	1.0000
8:125007420:A:AG	acceptor_gain	1.0000
8:125007421:G:GG	acceptor_gain	1.0000
8:125007483:TCAAG:T	donor_loss	1.0000
8:125007484:CAAG:C	donor_loss	1.0000
8:125007485:AAG:A	donor_loss	1.0000
8:125007486:AGG:A	donor_loss	1.0000
8:125007488:GTG:G	donor_loss	1.0000
8:125007489:T:G	donor_loss	1.0000
8:125009164:T:TA	acceptor_gain	1.0000
8:125009167:TTTA:T	acceptor_loss	1.0000
8:125009168:TTA:T	acceptor_loss	1.0000

AlphaMissense

3733 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:125018145:T:A	W431R	0.992
8:125018145:T:C	W431R	0.992
8:125005681:G:C	R234P	0.991
8:125009263:G:C	R343P	0.990
8:125018697:G:C	A472P	0.990
8:125020799:T:C	L487P	0.988
8:125018133:G:C	D427H	0.987
8:125007453:T:A	V263D	0.986
8:125008993:T:A	V282D	0.986
8:125021868:A:C	S550R	0.986
8:125021870:T:A	S550R	0.986
8:125021870:T:G	S550R	0.986
8:125018134:A:C	D427A	0.983
8:125008987:T:C	L280P	0.982
8:125008996:T:A	V283D	0.982
8:125018093:G:C	R413S	0.982
8:125018093:G:T	R413S	0.982
8:125009269:T:C	L345P	0.981
8:125018095:A:G	H414R	0.981
8:125018701:T:C	L473P	0.981
8:124999407:T:A	W2R	0.980
8:124999407:T:C	W2R	0.980
8:125009071:G:A	G308D	0.980
8:125018092:G:T	R413M	0.980
8:125021787:T:C	F523L	0.980
8:125021789:C:A	F523L	0.980
8:125021789:C:G	F523L	0.980
8:125003336:T:A	V151D	0.979
8:125007458:T:G	Y265D	0.979
8:125018074:G:T	G407V	0.979

dbSNP variants (sampled 300 via entrez): RS1000201348 (8:125006821 CAGCCTCCCGAGT>C), RS1000310240 (8:125007106 A>T), RS1000355779 (8:125013489 A>T), RS1000958458 (8:124996917 T>C), RS1001209805 (8:125015981 A>G), RS1001487613 (8:125009755 T>C), RS1001626505 (8:124998285 G>A), RS1001653907 (8:125001937 A>G), RS1001744073 (8:124998163 C>G,T), RS1001838721 (8:125000210 G>A), RS1001965139 (8:125006120 G>A), RS1002079678 (8:124996525 G>A), RS1002102388 (8:125006350 G>C), RS1002329500 (8:125012727 C>T), RS1002354978 (8:125008737 A>G)

Disease associations

OMIM: gene MIM:602019 | disease phenotypes: MIM:143890

GenCC curated gene-disease

Mondo (1): hypercholesterolemia, familial, 1 (MONDO:0007750)

Orphanet (1): Homozygous familial hypercholesterolemia (Orphanet:391665)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002509_3	Amyotrophic lateral sclerosis	5.000000e-06
GCST002510_1	Amyotrophic lateral sclerosis or frontotemporal dementia	1.000000e-07
GCST009391_1772	Metabolite levels	6.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0010478	fructose-1-phosphate measurement
EFO:0010479	fructose-6-phosphate measurement
EFO:0010484	glucose-1-phosphate measurement
EFO:0010485	glucose-6-phosphate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3592 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 62,729 (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
CHEMBL822	TERBINAFINE	4	33,025

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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 1b [PMID: 9871762]	Inhibition	7.22	pIC50

ChEMBL bioactivities

60 potent at pChembl≥5 of 67 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	IC50	20	nM	CHEMBL15929
7.70	IC50	20	nM	CHEMBL27885
7.52	Ki	30	nM	TERBINAFINE
7.52	IC50	30	nM	CHEMBL108692
7.52	IC50	30	nM	CHEMBL107546
7.30	IC50	50	nM	CHEMBL281025
7.22	IC50	60	nM	CHEMBL281025
7.22	IC50	60	nM	CHEMBL324433
7.16	IC50	70	nM	CHEMBL326008
7.16	IC50	70	nM	CHEMBL107608
7.16	IC50	70	nM	CHEMBL107568
7.10	IC50	80	nM	CHEMBL281025
7.05	IC50	90	nM	CHEMBL26950
7.05	IC50	90	nM	CHEMBL27154
7.05	IC50	90	nM	CHEMBL322059
7.00	IC50	100	nM	CHEMBL16178
7.00	IC50	100	nM	CHEMBL434507
7.00	IC50	100	nM	CHEMBL323953
6.92	IC50	120	nM	CHEMBL110608
6.89	IC50	130	nM	CHEMBL108144
6.82	IC50	150	nM	CHEMBL26151
6.82	IC50	150	nM	CHEMBL111126
6.82	IC50	150	nM	CHEMBL326241
6.77	IC50	170	nM	CHEMBL26964
6.77	IC50	170	nM	CHEMBL26596
6.70	IC50	200	nM	CHEMBL282077
6.70	IC50	200	nM	CHEMBL284197
6.68	IC50	210	nM	CHEMBL27941
6.68	IC50	210	nM	CHEMBL326204
6.64	IC50	230	nM	CHEMBL26077
6.60	IC50	250	nM	CHEMBL26597
6.59	IC50	255	nM	CHEMBL281666
6.57	IC50	270	nM	CHEMBL267332
6.54	IC50	290	nM	CHEMBL26723
6.52	IC50	300	nM	CHEMBL25755
6.48	IC50	330	nM	CHEMBL27365
6.41	IC50	390	nM	CHEMBL26592
6.40	IC50	400	nM	CHEMBL321207
6.35	IC50	450	nM	CHEMBL280972
6.28	IC50	520	nM	CHEMBL16004
6.06	IC50	870	nM	CHEMBL111114
6.02	IC50	960	nM	CHEMBL16120
6.00	IC50	1000	nM	CHEMBL109348
6.00	IC50	1000	nM	CHEMBL111684
5.75	IC50	1800	nM	CHEMBL26091
5.62	Ki	2400	nM	CHEMBL423562
5.52	IC50	3000	nM	CHEMBL107838
5.40	IC50	4000	nM	CHEMBL416643
5.40	IC50	4000	nM	TRISNORSQUALENE ALCOHOL
5.40	Ki	4000	nM	CHEMBL312758

PubChem BioAssay actives

51 with measured affinity, of 81 total; 48 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]methyl-dimethylsilyl]benzonitrile	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.0200	uM
(E)-N-ethyl-6,6-dimethyl-N-[[3-[(4-thiophen-3-ylthiophen-2-yl)methoxy]phenyl]methyl]hept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.0200	uM
(E)-N-[[3-[[dimethyl-(2-methylphenyl)silyl]methoxy]phenyl]methyl]-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.0300	uM
Terbinafine	204513: Inhibitory activity against Candida albicans Squalene Epoxidase	ki	0.0300	uM
2-[[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]methyl-dimethylsilyl]benzonitrile	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.0300	uM
N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-methylthiophene-2-sulfonamide	204660: In vitro inhibition of pig liver squalene epoxidase in HepG2 cells	ic50	0.0500	uM
(E)-N-ethyl-N-[[3-[[(4-fluorophenyl)-dimethylsilyl]methoxy]phenyl]methyl]-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.0600	uM
N-[[3-[[dimethyl-(2-methylphenyl)silyl]methoxy]phenyl]methyl]-N-ethyl-6-methoxy-6-methylhepta-2,4-diyn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.0700	uM
(E)-N-[[3-[[(4-ethenylphenyl)-dimethylsilyl]methoxy]phenyl]methyl]-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.0700	uM
(E)-N-[[3-[[dimethyl-[2-(trifluoromethyl)phenyl]silyl]methoxy]phenyl]methyl]-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.0700	uM
N-[[3-[[dimethyl-(2-methylphenyl)silyl]methoxy]phenyl]methyl]-N-ethyl-6,6-dimethylhepta-2,4-diyn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.0900	uM
N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-methyl-4-thiophen-3-ylthiophene-2-sulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.0900	uM
N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-ethylthiophene-2-sulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.0900	uM
4-[[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]methyl-dimethylsilyl]benzaldehyde	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.1000	uM
(E)-N-[[3-[[dimethyl-(4-methylphenyl)silyl]methoxy]phenyl]methyl]-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.1200	uM
(E)-N-[[3-[[benzyl(dimethyl)silyl]methoxy]phenyl]methyl]-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.1300	uM
(E)-N-ethyl-N-[[3-[[(2-methoxyphenyl)-dimethylsilyl]methoxy]phenyl]methyl]-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.1500	uM
N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-methylpyridine-3-sulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.1500	uM
(E)-N-[[3-[[dimethyl(phenyl)silyl]methoxy]phenyl]methyl]-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.1500	uM
N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-methyl-1,3-thiazole-2-sulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.1700	uM
N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-propylthiophene-2-sulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.1700	uM
4-cyano-N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-methylbenzenesulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.2000	uM
N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-methyl-1-thiophen-2-ylmethanesulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.2000	uM
(E)-N-[[3-[[(4-bromophenyl)-dimethylsilyl]methoxy]phenyl]methyl]-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.2100	uM
N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-methyl-5-thiophen-3-ylthiophene-2-sulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.2100	uM
N-cyclopropyl-N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]thiophene-2-sulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.2300	uM
N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-methylthiophene-3-sulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.2500	uM
N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-4-fluoro-N-methylbenzenesulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.2550	uM
(E)-N-ethyl-6,6-dimethyl-N-[[3-(3-thiophen-2-ylsulfonylpropoxy)phenyl]methyl]hept-2-en-4-yn-1-amine	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.2900	uM
4-bromo-N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-methylthiophene-2-sulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.3000	uM
4-bromo-N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-methylbenzenesulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.3300	uM
5-bromo-N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-methylthiophene-2-sulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.3900	uM
(E)-N-[[3-[[(4-chlorophenyl)-dimethylsilyl]methoxy]phenyl]methyl]-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.4000	uM
N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]thiophene-2-sulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	0.4500	uM
(E)-N-ethyl-N-[[3-[[(4-methoxyphenyl)-dimethylsilyl]methoxy]phenyl]methyl]-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	0.8700	uM
(E)-N-[[3-[[dimethyl-(4-methylsulfanylphenyl)silyl]methoxy]phenyl]methyl]-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	1.0000	uM
(E)-N-ethyl-N-[[3-[[(4-ethynylphenyl)-dimethylsilyl]methoxy]phenyl]methyl]-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	1.0000	uM
N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-methyl-1-benzothiophene-2-sulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	1.8000	uM
(E)-N-[[3-[[dimethyl-(3-methylphenyl)silyl]methoxy]phenyl]methyl]-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	3.0000	uM
(4E,8E,12E,16E)-4,8,13,17,21-pentamethyldocosa-4,8,12,16,20-pentaen-1-ol	204644: Inhibition of pig liver squalene epoxidase	ic50	4.0000	uM
(5E,9E,13E,17E)-5,9,14,18,22-pentamethyltricosa-5,9,13,17,21-pentaen-1-ol	204644: Inhibition of pig liver squalene epoxidase	ic50	4.0000	uM
4-[[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]methyl-dimethylsilyl]benzamide	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	5.0000	uM
1-[4-[[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]methyl-dimethylsilyl]phenyl]-2,2,2-trifluoroethanone	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	5.0000	uM
N-[3-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]propyl]-N-methylthiophene-2-sulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	6.4000	uM
4-[[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]methyl-dimethylsilyl]benzenethiol	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	8.0000	uM
4-[[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]methyl-dimethylsilyl]phenol	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	8.0000	uM
(E)-N-[[3-[[dimethyl-(2-thiophen-3-ylphenyl)silyl]methoxy]phenyl]methyl]-N-ethyl-6,6-dimethylhept-2-en-4-yn-1-amine	204661: In vitro inhibitory activity against pig liver microsomal squalene epoxidase	ic50	10.0000	uM
N-[2-[3-[[[(E)-6,6-dimethylhept-2-en-4-ynyl]-ethylamino]methyl]phenoxy]ethyl]-N-methyl-5-thiophen-2-ylthiophene-2-sulfonamide	86567: In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
bisphenol A	increases expression, affects expression, decreases expression	4
perfluorooctanoic acid	decreases expression, increases expression	4
sodium arsenite	decreases expression, increases abundance, increases expression	3
perfluorooctane sulfonic acid	decreases expression	3
Benzo(a)pyrene	decreases expression, increases methylation	3
Cyclosporine	decreases expression, increases expression	3
cobaltous chloride	decreases expression, affects cotreatment, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	2
chloropicrin	decreases expression	2
monomethylarsonous acid	decreases expression	2
bisphenol S	affects expression, affects cotreatment, increases expression	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Zoledronic Acid	increases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Doxorubicin	decreases expression	2
Formaldehyde	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tunicamycin	decreases expression	2
Zearalenone	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
Copper Sulfate	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
febrifugine	decreases expression	1

ChEMBL screening assays

23 unique, capped per target: 21 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL693810	Functional	In vitro inhibition of cholesterol biosynthesis in human HepG2 cells.	Sulfonamide derivatives of benzylamine block cholesterol biosynthesis in HepG2 cells: a new type of potent squalene epoxidase inhibitors. — Bioorg Med Chem Lett
CHEMBL806128	Binding	Inhibitory activity against Candida albicans Squalene Epoxidase	Squalene analogues containing isopropylidene mimics as potential inhibitors of pig liver squalene epoxidase and oxidosqualene cyclase. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2HA	Abcam HeLa SQLE KO	Cancer cell line	Female
CVCL_TQ31	HAP1 SQLE (-) 1	Cancer cell line	Male
CVCL_TQ32	HAP1 SQLE (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06231459	PHASE4	COMPLETED	Expression of Pro- and Anti-inflammatory Cytokines During Anti-PCSK9 in Familial Hypercholesterolemia
NCT00000594	PHASE3	COMPLETED	NHLBI Type II Coronary Intervention Study
NCT00092833	PHASE3	TERMINATED	Investigational Drug in Patients With Hypercholesterolemia or in Patients With Sitosterolemia (0653-026)(COMPLETED)
NCT00134485	PHASE3	COMPLETED	Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia
NCT00134511	PHASE3	COMPLETED	Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
NCT00136981	PHASE3	COMPLETED	Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone.
NCT00384293	PHASE3	TERMINATED	Carotid IMT (Intima Media Thickening) Study (0524A-041)(TERMINATED)
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NCT00280995	PHASE2	COMPLETED	Dose-escalating Safety Study of ISIS 301012 in Homozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT00281008	PHASE2	COMPLETED	Study of ISIS 301012 (Mipomersen) in Heterozygous Familial Hypercholesterolemia Subjects on Lipid Lowering Therapy
NCT01375751	PHASE2	COMPLETED	Reduction of Low-Density Lipoprotein Cholesterol (LDL-C) With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study
NCT00515307	PHASE1	COMPLETED	Bone Marrow Stem Cells as a Source of Allogenic Hepatocyte Transplantation in Homozygous Familial Hypercholesterolemia
NCT01583647	PHASE1	TERMINATED	A Study of Extended-release (ER) Niacin/Laropiprant in Adolescents With Heterozygous Familial Hypercholesterolemia (MK-0524A-158)
NCT00005168	Not specified	COMPLETED	Hyperapo B and Coronary Heart Disease
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NCT03018678	Not specified	COMPLETED	Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
NCT03110432	Not specified	COMPLETED	Prospective German Very High Cardiovascular Risk Patients Dyslipidemia Treatment Indication Registry
NCT03795038	Not specified	COMPLETED	Comparison of the Plasma Lipoprotein Apheresis Systems DIAMED and MONET vs. the Whole Blood Apheresis System DALI
NCT03989167	Not specified	RECRUITING	Clinical Decision Support for Familial Hypercholesterolemia
NCT04073797	Not specified	RECRUITING	PET Imaging of Inflammation and Lipid Lowering Study
NCT04118348	Not specified	COMPLETED	Evaluating the Efficacy of Pediatric Lipid Screening Alerts
NCT04313270	Not specified	UNKNOWN	Subclinical Atherosclerosis in Patients With Familial Hypercholesterolemia Treated With Evolocumab®
NCT04526457	Not specified	COMPLETED	Is Family Screening Improved by Genetic Testing of Familial Hypercholesterolemia
NCT04656028	Not specified	ACTIVE_NOT_RECRUITING	Genetic Testing and Motivational Counseling for FH
NCT04722068	Not specified	COMPLETED	Regeneron 1331 Kinetics Sub-Study HoFH
NCT04837638	Not specified	UNKNOWN	Diet Quality and Coronary Artery Calcification in Adults With Heterozygous Familial Hypercholesterolemia
NCT06555120	Not specified	RECRUITING	Screening for Familial Hypercholesterolemia in Children
NCT07543731	Not specified	NOT_YET_RECRUITING	A Real-World Study of Long-Term Adherence and Persistence to Inclisiran, Evolocumab, and Alirocumab