LSS

Summary

LSS (lanosterol synthase, HGNC:6708) is a protein-coding gene on chromosome 21q22.3, encoding Lanosterol synthase (P48449). Key enzyme in the cholesterol biosynthesis pathway.

The protein encoded by this gene catalyzes the conversion of (S)-2,3 oxidosqualene to lanosterol. The encoded protein is a member of the terpene cyclase/mutase family and catalyzes the first step in the biosynthesis of cholesterol, steroid hormones, and vitamin D. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 4047 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cataract 44 (Strong, GenCC) — +5 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 389 total — 20 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 55
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_002340

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6708
Approved symbol	LSS
Name	lanosterol synthase
Location	21q22.3
Locus type	gene with protein product
Status	Approved
Aliases	OSC
Ensembl gene	ENSG00000160285
Ensembl biotype	protein_coding
OMIM	600909
Entrez	4047

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 21 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000356396, ENST00000397728, ENST00000419093, ENST00000450351, ENST00000457828, ENST00000464357, ENST00000472272, ENST00000474319, ENST00000484808, ENST00000491729, ENST00000522411, ENST00000908050, ENST00000908051, ENST00000908052, ENST00000908053, ENST00000908054, ENST00000908055, ENST00000937737, ENST00000937738, ENST00000937739, ENST00000937740, ENST00000957229, ENST00000957230, ENST00000957231, ENST00000957232, ENST00000957233

RefSeq mRNA: 4 — MANE Select: NM_002340 NM_001001438, NM_001145436, NM_001145437, NM_002340

CCDS: CCDS13733, CCDS46654, CCDS54489

Canonical transcript exons

ENST00000397728 — 22 exons

Exon	Start	End
ENSE00001051152	46205836	46205941
ENSE00001051158	46215180	46215298
ENSE00001051167	46194491	46194661
ENSE00001051174	46209554	46209625
ENSE00001051175	46210688	46210744
ENSE00001051179	46208251	46208301
ENSE00001051181	46213738	46213835
ENSE00001051182	46191881	46191959
ENSE00001051183	46196202	46196267
ENSE00001051185	46206672	46206768
ENSE00001285727	46207428	46207577
ENSE00001296974	46213025	46213052
ENSE00003470036	46228434	46228599
ENSE00003491878	46222630	46222738
ENSE00003493068	46188446	46191235
ENSE00003493443	46195676	46195756
ENSE00003500657	46215685	46215793
ENSE00003525946	46219476	46219572
ENSE00003532484	46221854	46221975
ENSE00003581204	46227552	46227690
ENSE00003648196	46228732	46228774
ENSE00003784869	46216389	46216524

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.5777 / max 668.0896, expressed in 1823 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
190920	64.7968	1823
190919	1.3405	679
190918	0.4404	127

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of stomach	UBERON:0001199	98.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.83	gold quality
skin of leg	UBERON:0001511	97.48	gold quality
zone of skin	UBERON:0000014	97.34	gold quality
right ovary	UBERON:0002118	97.32	gold quality
skin of abdomen	UBERON:0001416	97.25	gold quality
corpus callosum	UBERON:0002336	97.25	gold quality
pituitary gland	UBERON:0000007	97.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.06	gold quality
ventricular zone	UBERON:0003053	97.04	gold quality
left ovary	UBERON:0002119	96.79	gold quality
cerebellar hemisphere	UBERON:0002245	96.69	gold quality
cerebellum	UBERON:0002037	96.65	gold quality
cerebellar cortex	UBERON:0002129	96.64	gold quality
ectocervix	UBERON:0012249	96.57	gold quality
adenohypophysis	UBERON:0002196	96.40	gold quality
ovary	UBERON:0000992	96.31	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.30	gold quality
ganglionic eminence	UBERON:0004023	96.18	gold quality
right lung	UBERON:0002167	96.12	gold quality
substantia nigra	UBERON:0002038	96.04	gold quality
right adrenal gland cortex	UBERON:0035827	95.97	gold quality
right adrenal gland	UBERON:0001233	95.92	gold quality
hypothalamus	UBERON:0001898	95.91	gold quality
tibial nerve	UBERON:0001323	95.66	gold quality
apex of heart	UBERON:0002098	95.50	gold quality
body of uterus	UBERON:0009853	95.45	gold quality
adrenal tissue	UBERON:0018303	95.44	gold quality
esophagus mucosa	UBERON:0002469	95.42	gold quality
vagina	UBERON:0000996	95.31	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HDAC3, YY1

miRNA regulators (miRDB)

16 targeting LSS, 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-4493	99.90	66.48	977
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-6811-3P	98.62	66.54	944
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-640	98.44	66.93	644
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-6747-3P	97.73	64.84	1596
HSA-MIR-335-5P	97.10	68.12	1022

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• oxidosqualene cyclase is active as a monomer (PMID:14766201)
• two crystal structures of the human membrane protein OSC: the target protein with an inhibitor that showed cholesterol lowering in vivo opens the way for the structure-based design of new OSC inhibitors (PMID:15525992)
• Suppression of 2,3-oxidosqualene cyclase by high fat diet contributes to liver X receptor-alpha-mediated improvement of hepatic lipid profile. (PMID:19119143)
• There were no significant differences in OSC mRNA expression at various stages of breast cancer, or between tumor and normal mammary cells. (PMID:25051231)
• Lanosterol synthase gene polymorphisms influence both the salt sensitivity of BP and changes in circulating EO in response to a low salt diet. (PMID:26667413)
• LSS gene mutation is associated with Congenital cataract. (PMID:29016354)
• In the cholesterol biosynthesis pathway, lanosterol synthase leads to the cyclization of (S)-2,3-oxidosqualene into lanosterol. Our data suggest LSS as a major gene causing a rare recessive neuroectodermal syndrome. (PMID:30723320)
• Investigated lanosterol synthase as a possible target for treatment of glioma. (PMID:30923116)
• Study describes identification of novel mutation 1885T>A (p.Trp629Arg) in the LSS gene in the squalene cyclase, C-terminal domain associated with hypotrichosis 14 in a Chinese family. (PMID:31322293)
• Study identified two patients with novel biallelic LSS mutations who exhibited congenital hypotrichosis and midline anomalies but did not have cataracts. Epidermis-specific Lss knockout mice showed neonatal lethality due to dehydration, indicating that LSS could be involved in skin barrier integrity. Knockout of Lss in the epidermis caused hypotrichosis in adult mice. Lens-specific Lss knockout mice had cataracts. (PMID:32101538)
• The Polymorphism rs2968 of LSS Gene Confers Susceptibility to Age-Related Cataract. (PMID:32877255)
• Novel mutations in Chinese hypotrichosis simplex patients associated with LSS gene. (PMID:33222230)
• Four hypotrichosis families with mutations in the gene LSS presenting with and without neurodevelopmental phenotypes. (PMID:34318586)
• LSS rs2254524 Increases the Risk of Hypertension in Children and Adolescents with Obesity. (PMID:37628669)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lss	ENSDARG00000061274
mus_musculus	Lss	ENSMUSG00000033105
rattus_norvegicus	Lss	ENSRNOG00000054549

Protein

Protein identifiers

Lanosterol synthase — P48449 (reviewed: P48449)

Alternative names: 2,3-epoxysqualene–lanosterol cyclase, Oxidosqualene–lanosterol cyclase

All UniProt accessions (3): P48449, C9J315, H7C3A5

UniProt curated annotations — full annotation on UniProt →

Function. Key enzyme in the cholesterol biosynthesis pathway. Catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol nucleus. Through the production of lanosterol may regulate lens protein aggregation and increase transparency.

Subunit / interactions. Monomer.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed. Expressed in the hair bulb, the outer root sheath and hair matrix of the hair follicle epithelium. Also detected in dermal papilla, epidermis, sweat glands, sebaceous glands, and blood vessels.

Disease relevance. Cataract 44 (CTRCT44) [MIM:616509] An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. The disease is caused by variants affecting the gene represented in this entry. Hypotrichosis 14 (HYPT14) [MIM:618275] A form of hypotrichosis, a condition characterized by the presence of less than the normal amount of hair and abnormal hair follicles and shafts, which are thin and atrophic. The extent of scalp and body hair involvement can be very variable, within as well as between families. HYPT14 is an autosomal recessive form characterized by sparse to absent lanugo-like scalp hair, sparse and brittle eyebrows, and sparse eyelashes and body hair. The disease is caused by variants affecting the gene represented in this entry. Alopecia-intellectual disability syndrome 4 (APMR4) [MIM:618840] An autosomal recessive disorder characterized by alopecia universalis, scaly skin, mild to severe intellectual disability, delayed or absent speech, and motor delay. The disease is caused by variants affecting the gene represented in this entry.

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

Similarity. Belongs to the terpene cyclase/mutase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P48449-1	1	yes
P48449-2	2
P48449-3	3

RefSeq proteins (4): NP_001001438, NP_001138908, NP_001138909, NP_002331* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002365	Terpene_synthase_CS	Conserved_site
IPR008930	Terpenoid_cyclase/PrenylTrfase	Homologous_superfamily
IPR018333	Squalene_cyclase	Family
IPR032696	SQ_cyclase_C	Domain
IPR032697	SQ_cyclase_N	Domain

Pfam: PF13243, PF13249

Enzyme classification (BRENDA):

• EC 5.4.99.7 — Lanosterol synthase (BRENDA: 20 organisms, 41 substrates, 291 inhibitors, 7 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
2,3-EPOXYSQUALENE	0.015–0.035	3
(3S)-2,3-EPOXY-2,3-DIHYDROSQUALENE	0.075	1
(3S)-2,3-OXIDOSQUALENE	0.011	1
(3S)-SQUALENE EPOXIDE	0.055	1
3-[(3E,7E,15E)-16-ETHYL-3,7,12,20-TETRAMETHYLHEN	0.231	1

Catalyzed reactions (Rhea), 1 shown:

• (S)-2,3-epoxysqualene = lanosterol (RHEA:14621)

UniProt features (93 total): helix 39, sequence variant 22, strand 12, repeat 7, site 3, turn 3, splice variant 2, initiator methionine 1, chain 1, modified residue 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1W6K	X-RAY DIFFRACTION	2.1
1W6J	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48449-F1	98.05	0.98

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 (4): 387 (transition state stabilizer); 444 (transition state stabilizer); 581 (transition state stabilizer); 455 (proton donor)

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2426168	Activation of gene expression by SREBF (SREBP)
R-HSA-9969896	Lanosterol biosynthesis
R-HSA-191273	Cholesterol biosynthesis
R-HSA-1430728	Metabolism
R-HSA-1655829	Regulation of cholesterol biosynthesis by SREBP (SREBF)
R-HSA-556833	Metabolism of lipids
R-HSA-8957322	Metabolism of steroids

MSigDB gene sets: 332 (showing top): GRUETZMANN_PANCREATIC_CANCER_DN, MODULE_522, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, BILD_SRC_ONCOGENIC_SIGNATURE, TERAMOTO_OPN_TARGETS_CLUSTER_1, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, MORF_SKP1A, GERY_CEBP_TARGETS, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_STEROID_BIOSYNTHETIC_PROCESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (5): steroid biosynthetic process (GO:0006694), cholesterol biosynthetic process (GO:0006695), triterpenoid biosynthetic process (GO:0016104), regulation of protein stability (GO:0031647), lipid metabolic process (GO:0006629)

GO Molecular Function (4): lanosterol synthase activity (GO:0000250), protein binding (GO:0005515), isomerase activity (GO:0016853), intramolecular transferase activity (GO:0016866)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), lipid droplet (GO:0005811), membrane (GO:0016020), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Metabolism of steroids	2
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1
Cholesterol biosynthesis	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
steroid metabolic process	1
lipid biosynthetic process	1
cholesterol metabolic process	1
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
triterpenoid metabolic process	1
terpenoid biosynthetic process	1
regulation of biological quality	1
primary metabolic process	1
oxidosqualene cyclase activity	1
binding	1
catalytic activity	1
isomerase activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intracellular membraneless organelle	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1374 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LSS	FDFT1	P37268	968
LSS	SQLE	Q14534	841
LSS	MVD	P53602	763
LSS	CYP51A1	Q16850	748
LSS	HMGCR	P04035	744
LSS	DHCR24	Q15392	735
LSS	HMGCS1	Q01581	734
LSS	DHCR7	Q9UBM7	730
LSS	NSDHL	Q15738	729
LSS	SC5D	O75845	718
LSS	MVK	Q03426	717
LSS	IDI1	Q13907	716
LSS	FDPS	P14324	715
LSS	MSMO1	Q15800	713
LSS	TM7SF2	O76062	702

IntAct

77 interactions, top by confidence:

A	B	Type	Score
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
SUMO1	CBX4	psi-mi:“MI:0914”(association)	0.600
LSS	CIB1	psi-mi:“MI:0915”(physical association)	0.560
YIF1A	LSS	psi-mi:“MI:0915”(physical association)	0.560
LSS	TMEM167B	psi-mi:“MI:0915”(physical association)	0.560
LSS	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
LSS	TMEM86B	psi-mi:“MI:0915”(physical association)	0.560
LSS	SLC10A6	psi-mi:“MI:0915”(physical association)	0.560
LSS	AQP6	psi-mi:“MI:0915”(physical association)	0.560
ALOX5	DDHD2	psi-mi:“MI:0914”(association)	0.530
APP	LSS	psi-mi:“MI:0915”(physical association)	0.370
LSS	GPR35	psi-mi:“MI:0915”(physical association)	0.370
NR4A1	LSS	psi-mi:“MI:0915”(physical association)	0.370
MYH9	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Klc2	MTA3	psi-mi:“MI:0914”(association)	0.350
FIP1L1	WWP2	psi-mi:“MI:0914”(association)	0.350
MYO5C	CLIC1	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
TNFRSF10A	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
PNKD	EXOC5	psi-mi:“MI:0914”(association)	0.350
GATD1		psi-mi:“MI:0914”(association)	0.350
LYPD4	DPYSL4	psi-mi:“MI:0914”(association)	0.350
GML	CLSTN1	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
KLF15	COL6A1	psi-mi:“MI:0914”(association)	0.350
NUTM2F	IRF6	psi-mi:“MI:0914”(association)	0.350

BioGRID (111): LSS (Affinity Capture-MS), LSS (Affinity Capture-MS), LSS (Affinity Capture-MS), LSS (Affinity Capture-MS), LSS (Affinity Capture-MS), LSS (Affinity Capture-MS), LSS (Affinity Capture-MS), LSS (Affinity Capture-MS), LSS (Affinity Capture-MS), LSS (Affinity Capture-MS), LSS (Affinity Capture-MS), LSS (Affinity Capture-MS), LSS (Affinity Capture-MS), LSS (Affinity Capture-RNA), LSS (Affinity Capture-MS)

ESM2 similar proteins: A0A067DDU9, A0A067FI21, A0A0S2IHL6, A0A0U2U4F3, A0A125SXN3, A0AAW1L0L7, A8C980, A8CDT2, A8CDT3, B6EXY6, B9X0J1, E2IUA6, E2IUA7, E2IUA8, E2IUA9, E2IUB0, E7DN63, E7DN64, F8WQD0, H2KWF1, K7NBZ9, O82139, O82140, O82146, P0C8Y0, P0DXI1, P38605, P48449, P48450, P84466, Q1G1A4, Q2R712, Q2XPU6, Q2XPU7, Q6BE23, Q6BE24, Q6BE25, Q6Z2X6, Q764T8, Q8BLN5

Diamond homologs: A0A067DDU9, A0A067ECN5, A0A067FI21, A0A0E0SP71, A0A0S2IHL6, A0A0U2U4F3, A0A125SXN1, A0A125SXN2, A0A125SXN3, A0A455LN86, A0A455LRW3, A0A5B8NBE6, A0A5B8NBN0, A0AAW1L0L7, A1CVK0, A8C980, A8C981, A8CDT2, A8CDT3, B0Y5B4, B6EXY6, B9X0J1, D7NJ68, E2IUA6, E2IUA7, E2IUA8, E2IUA9, E2IUB0, E4V6I8, E7DN63, E7DN64, F8WQD0, H2KWF1, K7NBZ9, O23390, O82139, O82140, O82146, P0C8Y0, P0DXI1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	20
Likely pathogenic	13
Uncertain significance	148
Likely benign	101
Benign	74

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1256057	NM_002340.6(LSS):c.647G>A (p.Trp216Ter)	Pathogenic
1707553	NM_002340.6(LSS):c.1955C>T (p.Thr652Ile)	Pathogenic
1966922	NM_002340.6(LSS):c.304del (p.Leu102fs)	Pathogenic
2084020	NM_002340.6(LSS):c.422G>A (p.Trp141Ter)	Pathogenic
2120289	NM_002340.6(LSS):c.443del (p.Lys148fs)	Pathogenic
221227	NM_002340.6(LSS):c.1741T>C (p.Trp581Arg)	Pathogenic
2227722	NM_002340.6(LSS):c.494del (p.Gly165fs)	Pathogenic
2500989	NM_002340.6(LSS):c.1522G>C (p.Gly508Arg)	Pathogenic
2500990	NM_002340.6(LSS):c.1016C>T (p.Ser339Leu)	Pathogenic
2972956	NM_002340.6(LSS):c.1810C>T (p.Arg604Ter)	Pathogenic
4751137	NM_002340.6(LSS):c.775del (p.Leu259fs)	Pathogenic
4805866	NM_002340.6(LSS):c.676_685dup (p.Leu229fs)	Pathogenic
599317	NM_002340.6(LSS):c.1025T>G (p.Ile342Ser)	Pathogenic
599320	NM_002340.6(LSS):c.743T>C (p.Leu248Pro)	Pathogenic
599321	NM_002340.6(LSS):c.304C>G (p.Leu102Val)	Pathogenic
599322	NM_002340.6(LSS):c.423G>A (p.Trp141Ter)	Pathogenic
834065	NM_002340.6(LSS):c.2114C>A (p.Thr705Lys)	Pathogenic
834066	NM_002340.6(LSS):c.779G>C (p.Arg260Pro)	Pathogenic
834068	NM_002340.6(LSS):c.35G>A (p.Gly12Asp)	Pathogenic
982379	NM_002340.6(LSS):c.1109+2T>C	Pathogenic
1098866	NM_002340.6(LSS):c.429-1G>A	Likely pathogenic
1256056	NM_002340.6(LSS):c.857A>G (p.Tyr286Cys)	Likely pathogenic
1707082	NM_002340.6(LSS):c.1702C>T (p.Arg568Trp)	Likely pathogenic
2861308	NM_002340.6(LSS):c.626A>T (p.Asn209Ile)	Likely pathogenic
3065729	NM_002340.6(LSS):c.1317+1G>T	Likely pathogenic
3121356	NM_002340.6(LSS):c.1565-2del	Likely pathogenic
3681234	NM_002340.6(LSS):c.1989-1G>A	Likely pathogenic
4072283	NM_002340.6(LSS):c.523C>T (p.Arg175Ter)	Likely pathogenic
4081501	NM_002340.6(LSS):c.1021del (p.Thr341fs)	Likely pathogenic
4813367	NM_002340.6(LSS):c.1670+1G>T	Likely pathogenic

SpliceAI

4929 predictions. Top by Δscore:

Variant	Effect	Δscore
21:46191064:A:AC	donor_gain	1.0000
21:46191065:C:CC	donor_gain	1.0000
21:46194580:AAAGT:A	donor_gain	1.0000
21:46195670:A:AC	donor_gain	1.0000
21:46195671:C:CC	donor_gain	1.0000
21:46195671:CTCA:C	donor_gain	1.0000
21:46195674:AC:A	donor_gain	1.0000
21:46195675:CC:C	donor_gain	1.0000
21:46195675:CCCAT:C	donor_gain	1.0000
21:46204757:A:AC	donor_gain	1.0000
21:46205883:AAGCG:A	donor_gain	1.0000
21:46205937:GTCCC:G	acceptor_gain	1.0000
21:46205938:TCCC:T	acceptor_gain	1.0000
21:46205938:TCCCC:T	acceptor_loss	1.0000
21:46205939:CCC:C	acceptor_gain	1.0000
21:46205939:CCCC:C	acceptor_gain	1.0000
21:46205940:CC:C	acceptor_gain	1.0000
21:46205940:CCC:C	acceptor_gain	1.0000
21:46205940:CCCTG:C	acceptor_loss	1.0000
21:46205941:CC:C	acceptor_gain	1.0000
21:46205942:C:CC	acceptor_gain	1.0000
21:46205942:C:T	acceptor_gain	1.0000
21:46205942:CTG:C	acceptor_loss	1.0000
21:46205943:T:A	acceptor_loss	1.0000
21:46206667:CTCA:C	donor_loss	1.0000
21:46206668:TCACC:T	donor_loss	1.0000
21:46206669:CA:C	donor_loss	1.0000
21:46206670:A:AC	donor_gain	1.0000
21:46206670:ACC:A	donor_loss	1.0000
21:46206671:C:A	donor_loss	1.0000

AlphaMissense

4773 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
21:46191215:G:C	F696L	0.999
21:46191215:G:T	F696L	0.999
21:46191217:A:G	F696L	0.999
21:46219549:A:G	W192R	0.999
21:46219549:A:T	W192R	0.999
21:46195752:A:G	W581R	0.998
21:46195752:A:T	W581R	0.998
21:46206673:G:C	F521L	0.998
21:46206673:G:T	F521L	0.998
21:46206675:A:G	F521L	0.998
21:46222637:A:G	W141R	0.998
21:46222637:A:T	W141R	0.998
21:46195750:C:A	W581C	0.997
21:46195750:C:G	W581C	0.997
21:46210723:A:G	W387R	0.997
21:46210723:A:T	W387R	0.997
21:46227562:G:C	F103L	0.997
21:46227562:G:T	F103L	0.997
21:46227564:A:G	F103L	0.997
21:46216484:A:G	W230R	0.996
21:46216484:A:T	W230R	0.996
21:46219547:C:A	W192C	0.996
21:46219547:C:G	W192C	0.996
21:46227591:A:G	W94R	0.996
21:46227591:A:T	W94R	0.996
21:46207544:A:G	W451R	0.995
21:46207544:A:T	W451R	0.995
21:46215184:C:T	G336D	0.995
21:46216471:C:G	R234P	0.995
21:46216478:G:C	H232D	0.995

dbSNP variants (sampled 300 via entrez): RS1000034682 (21:46208642 C>T), RS1000067711 (21:46212885 G>A), RS1000139810 (21:46213941 G>A,T), RS1000204364 (21:46190484 G>A), RS1000235069 (21:46228154 T>C), RS1000278232 (21:46193850 T>C), RS1000288262 (21:46193681 G>A,C), RS1000293730 (21:46217267 A>T), RS1000300290 (21:46227442 G>A), RS1000343428 (21:46208915 T>A,G), RS1000350839 (21:46222689 G>A), RS1000451658 (21:46205543 T>C,G), RS1000468500 (21:46222376 TGACA>T), RS1000671298 (21:46221011 C>T), RS1000672204 (21:46227849 G>A)

Disease associations

OMIM: gene MIM:600909 | disease phenotypes: MIM:616509, MIM:618840, MIM:618275

GenCC curated gene-disease

Disease	Classification	Inheritance
cataract 44	Strong	Autosomal recessive
hypotrichosis 14	Strong	Autosomal recessive
alopecia-intellectual disability syndrome 4	Strong	Autosomal recessive
hypotrichosis simplex	Supportive	Autosomal dominant
total early-onset cataract	Supportive	Autosomal dominant
autosomal recessive palmoplantar keratoderma and congenital alopecia	Limited	Autosomal recessive

Mondo (6): cataract 44 (MONDO:0014673), alopecia-intellectual disability syndrome 4 (MONDO:0030009), hypotrichosis 14 (MONDO:0032649), hypotrichosis simplex (MONDO:0018914), total early-onset cataract (MONDO:0021548), autosomal recessive palmoplantar keratoderma and congenital alopecia (MONDO:0008923)

Orphanet (2): Early onset non-syndromic cataract (Orphanet:91492), Total early-onset cataract (Orphanet:98994)

HPO phenotypes

55 total (30 of 55 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000252	Microcephaly
HP:0000365	Hearing impairment
HP:0000400	Macrotia
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000572	Visual loss
HP:0000613	Photophobia
HP:0000653	Sparse eyelashes
HP:0000713	Agitation
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000815	Hypergonadotropic hypogonadism
HP:0000962	Hyperkeratosis
HP:0000982	Palmoplantar keratoderma
HP:0000987	Atypical scarring of skin
HP:0001019	Erythroderma
HP:0001156	Brachydactyly
HP:0001171	Split hand
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001371	Flexion contracture
HP:0001387	Joint stiffness
HP:0001482	Subcutaneous nodule
HP:0001510	Growth delay
HP:0001596	Alopecia

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004610_99	White blood cell count	8.000000e-09
GCST012441_2	Glutathione peroxidase in non-alcoholic fatty liver disease x mastiha supplementation interaction	9.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0600067	mastiha supplement exposure measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C535336	Cataract, alopecia, sclerodactyly (supp.)
C537160	Hypotrichosis simplex (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3593 (SINGLE PROTEIN)

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 (16 total), top 16:

Ligand	Action	Affinity	Parameter
compound 4 [PMID: 9003518]	Inhibition	9.59	pIC50
29-methylidene-2,3-oxidosqualene	Inhibition	9.52	pIC50
compound 4 [PMID: 22533316]	Inhibition	8.54	pIC50
compound 8 [PMID: 22533316]	Inhibition	8.3	pIC50
Ro 48-8071	Inhibition	8.24	pIC50
compound 6 [PMID: 22533316]	Inhibition	8.11	pIC50
compound 1 [PMID: 22533316]	Inhibition	8.1	pIC50
compound 5 [PMID: 22533316]	Inhibition	8.0	pIC50
compound 9 [PMID: 22533316]	Inhibition	7.95	pIC50
compound 7 [PMID: 22533316]	Inhibition	7.9	pIC50
compound 3 [PMID: 22533316]	Inhibition	7.75	pIC50
compound 10 [PMID: 22533316]	Inhibition	7.54	pIC50
compound 3 [PMID: 9003518]	Inhibition	7.3	pIC50
compound 1 [Gotteland et al., 1997]	Inhibition	7.15	pIC50
compound 4b [Marquart et al., 1994]	Inhibition	6.77	pIC50
compound 4a [Marquart et al., 1994]	Inhibition	6.37	pIC50

ChEMBL bioactivities

201 potent at pChembl≥5 of 215 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.66	IC50	0.22	nM	CHEMBL64905
8.72	IC50	1.905	nM	CHEMBL609978
8.72	IC50	1.9	nM	CHEMBL542453
8.64	IC50	2.3	nM	CHEMBL63335
8.54	IC50	2.9	nM	CHEMBL112210
8.54	IC50	2.884	nM	CHEMBL67133
8.54	IC50	2.9	nM	CHEMBL67133
8.52	IC50	3	nM	CHEMBL482527
8.52	IC50	3	nM	CHEMBL63524
8.46	IC50	3.467	nM	CHEMBL65024
8.46	IC50	3.5	nM	CHEMBL65024
8.46	IC50	3.5	nM	CHEMBL543877
8.39	IC50	4.074	nM	CHEMBL611484
8.39	IC50	4.074	nM	CHEMBL66638
8.39	IC50	4.1	nM	CHEMBL66638
8.39	IC50	4.1	nM	CHEMBL115085
8.39	IC50	4.1	nM	CHEMBL116705
8.37	IC50	4.3	nM	CHEMBL135109
8.34	IC50	4.6	nM	CHEMBL115020
8.34	IC50	4.571	nM	CHEMBL611485
8.34	IC50	4.6	nM	CHEMBL135109
8.30	IC50	5	nM	CHEMBL448434
8.27	IC50	5.37	nM	CHEMBL416694
8.27	IC50	5.4	nM	CHEMBL416694
8.27	IC50	5.4	nM	CHEMBL114259
8.25	IC50	5.6	nM	CHEMBL116000
8.24	IC50	5.7	nM	CHEMBL324162
8.22	IC50	6	nM	CHEMBL484125
8.21	IC50	6.166	nM	CHEMBL611486
8.21	IC50	6.2	nM	CHEMBL115923
8.20	IC50	6.31	nM	CHEMBL611757
8.20	IC50	6.3	nM	CHEMBL115375
8.19	IC50	6.457	nM	CHEMBL304858
8.19	IC50	6.457	nM	CHEMBL293005
8.19	IC50	6.5	nM	CHEMBL304858
8.19	IC50	6.5	nM	CHEMBL324162
8.17	IC50	6.761	nM	CHEMBL611758
8.17	IC50	6.7	nM	CHEMBL554209
8.12	IC50	7.5	nM	CHEMBL304858
8.11	IC50	7.8	nM	CHEMBL2164235
8.11	IC50	7.762	nM	CHEMBL612024
8.11	IC50	7.8	nM	CHEMBL324034
8.10	IC50	8	nM	CHEMBL481608
8.10	IC50	7.943	nM	CHEMBL112693
8.10	IC50	7.9	nM	CHEMBL112693
8.06	IC50	8.71	nM	CHEMBL612025
8.06	IC50	8.7	nM	CHEMBL114266
8.00	IC50	10	nM	CHEMBL2164234
7.95	IC50	11.2	nM	CHEMBL2164237
7.95	IC50	11.3	nM	CHEMBL66412

PubChem BioAssay actives

197 with measured affinity, of 303 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
2,2-dimethyl-3-[(3E,7E,11E)-3,7,12-trimethyl-14-(6-methylhept-5-en-2-ylsulfanyl)tetradeca-3,7,11-trienyl]oxirane	151641: Compound was tested for inhibition of purified Oxidosqualene-lanosterol cyclase from Candida albicans	ic50	0.0002	uM
[4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]-(4-nitrophenyl)methanone	298048: Inhibition of oxidosqualene cyclase	ic50	0.0019	uM
[4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]-(4-nitrophenyl)methanone;hydrochloride	2978: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0019	uM
2,2-dimethyl-3-[(3E,7E,11E)-3,7,12-trimethyl-15-(4-methylpent-3-enylsulfanyl)pentadeca-3,7,11-trienyl]oxirane	151641: Compound was tested for inhibition of purified Oxidosqualene-lanosterol cyclase from Candida albicans	ic50	0.0023	uM
6-[[3-(4-bromophenyl)-1,2-benzothiazol-6-yl]oxy]-N-methyl-N-prop-2-enylhexan-1-amine;(E)-but-2-enedioic acid	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0029	uM
6-[[3-(4-bromophenyl)-1,2-benzothiazol-6-yl]oxy]-N-methyl-N-prop-2-enylhexan-1-amine	151650: Inhibitory activity against Oxidosqualene-lanosterol cyclase from human liver microsomes	ic50	0.0029	uM
(4-chlorophenyl)-[4-[(4-pyridin-4-ylphenyl)methyl]piperazin-1-yl]methanone	408086: Inhibition of 2,3-oxidosqualene-lanosterol cyclase	ic50	0.0030	uM
(4-bromophenyl)-[4-[(E)-4-[methyl(prop-2-enyl)amino]but-2-enoxy]phenyl]methanone	151650: Inhibitory activity against Oxidosqualene-lanosterol cyclase from human liver microsomes	ic50	0.0030	uM
6-[1-(4-bromophenyl)isoquinolin-6-yl]oxy-N-methyl-N-prop-2-enylhexan-1-amine	151650: Inhibitory activity against Oxidosqualene-lanosterol cyclase from human liver microsomes	ic50	0.0035	uM
6-[1-(4-bromophenyl)isoquinolin-6-yl]oxy-N-methyl-N-prop-2-enylhexan-1-amine;hydrochloride	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0035	uM
6-[[4-(4-bromophenyl)-1H-2,3-benzoxazin-7-yl]oxy]-N-methyl-N-prop-2-enylhexan-1-amine	151650: Inhibitory activity against Oxidosqualene-lanosterol cyclase from human liver microsomes	ic50	0.0041	uM
(4-bromophenyl)-[2-(methylamino)-4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]methanone	298048: Inhibition of oxidosqualene cyclase	ic50	0.0041	uM
(4-bromophenyl)-[2-(methylamino)-4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]methanone;(E)-but-2-enedioic acid	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0041	uM
6-[[4-(4-bromophenyl)-1H-2,3-benzoxazin-7-yl]oxy]-N-methyl-N-prop-2-enylhexan-1-amine;(E)-but-2-enedioic acid	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0041	uM
(E)-but-2-enedioic acid;(4-chlorophenyl)-[2-fluoro-4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]methanone	151646: Tested for Oxidosqualene-lanosterol cyclase inhibition in Trypanosoma brucei	ic50	0.0043	uM
(4-bromophenyl)-[2-methoxy-4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]methanone	298048: Inhibition of oxidosqualene cyclase	ic50	0.0046	uM
(4-bromophenyl)-[2-methoxy-4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]methanone;(E)-but-2-enedioic acid	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0046	uM
2-hydroxypropane-1,2,3-tricarboxylic acid;[4-(trifluoromethyl)phenyl] N-methyl-N-[4-[5-[methyl(prop-2-enyl)amino]pentyl]cyclohexyl]carbamate	699374: Inhibition of human liver microsome 2,3-OSC after 1 hr by Silica gel plate phosphor imaging	ic50	0.0050	uM
(4-bromophenyl)-[4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]methanone	151650: Inhibitory activity against Oxidosqualene-lanosterol cyclase from human liver microsomes	ic50	0.0054	uM
(4-bromophenyl)-[4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]methanone;(E)-but-2-enedioic acid	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0054	uM
6-[[3-(4-bromophenyl)-1-benzothiophen-6-yl]oxy]-N-methyl-N-prop-2-enylhexan-1-amine;(E)-but-2-enedioic acid	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0056	uM
(4-bromophenyl)-[2-fluoro-4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]methanone;(E)-but-2-enedioic acid	699374: Inhibition of human liver microsome 2,3-OSC after 1 hr by Silica gel plate phosphor imaging	ic50	0.0057	uM
1-[4-[[4-(4-chlorophenyl)sulfonylpiperazin-1-yl]methyl]phenyl]-4-methylpiperazine	408086: Inhibition of 2,3-oxidosqualene-lanosterol cyclase	ic50	0.0060	uM
(4-bromophenyl)-[4-[6-[methyl(prop-2-enyl)amino]hexoxy]-2-methylsulfanylphenyl]methanone	298048: Inhibition of oxidosqualene cyclase	ic50	0.0062	uM
(4-bromophenyl)-[4-[6-[methyl(prop-2-enyl)amino]hexoxy]-2-methylsulfanylphenyl]methanone;(E)-but-2-enedioic acid	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0062	uM
(4-bromophenyl)-[2-hydroxy-4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]methanone	298048: Inhibition of oxidosqualene cyclase	ic50	0.0063	uM
(4-bromophenyl)-[2-hydroxy-4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]methanone;(E)-but-2-enedioic acid	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0063	uM
(4-bromophenyl)-[2-fluoro-4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]methanone	151650: Inhibitory activity against Oxidosqualene-lanosterol cyclase from human liver microsomes	ic50	0.0065	uM
(4-bromophenyl)-[4-[[(1S,2S)-2-[[cyclopropyl(prop-2-enyl)amino]methyl]cyclopropyl]methoxy]phenyl]methanone	371186: Inhibition of oxidosqualene cyclase	ic50	0.0065	uM
(4-fluorophenyl)-[4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]methanone;hydrochloride	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0067	uM
(4-fluorophenyl)-[4-[6-[methyl(prop-2-enyl)amino]hexoxy]phenyl]methanone	298048: Inhibition of oxidosqualene cyclase	ic50	0.0068	uM
6-[[3-(4-bromophenyl)-1,1-dioxo-1,2-benzothiazol-6-yl]oxy]-N-methyl-N-prop-2-enylhexan-1-amine;(E)-but-2-enedioic acid	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0078	uM
6-[[3-(4-bromophenyl)-1,1-dioxo-1-benzothiophen-6-yl]oxy]-N-methyl-N-prop-2-enylhexan-1-amine	298048: Inhibition of oxidosqualene cyclase	ic50	0.0078	uM
(E)-but-2-enedioic acid;(4-chlorophenyl) N-methyl-N-[4-[5-[methyl(propyl)amino]pent-1-ynyl]cyclohexyl]carbamate	699374: Inhibition of human liver microsome 2,3-OSC after 1 hr by Silica gel plate phosphor imaging	ic50	0.0078	uM
6-[[1-(4-bromophenyl)-3,4-dihydroisoquinolin-6-yl]oxy]-N-methyl-N-prop-2-enylhexan-1-amine	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0079	uM
(4-bromophenyl)-[4-[4-[[methyl(prop-2-enyl)amino]methyl]phenyl]phenyl]methanone;hydrochloride	699374: Inhibition of human liver microsome 2,3-OSC after 1 hr by Silica gel plate phosphor imaging	ic50	0.0080	uM
(4-bromophenyl)-[6-[6-[methyl(prop-2-enyl)amino]hexoxy]-3-pyridinyl]methanone	298048: Inhibition of oxidosqualene cyclase	ic50	0.0087	uM
(4-bromophenyl)-[6-[6-[methyl(prop-2-enyl)amino]hexoxy]-3-pyridinyl]methanone;(E)-but-2-enedioic acid	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0087	uM
(4-chlorophenyl) N-[4-[5-[ethyl(2-hydroxyethyl)amino]pent-1-ynyl]cyclohexyl]-N-methylcarbamate;hydrochloride	699374: Inhibition of human liver microsome 2,3-OSC after 1 hr by Silica gel plate phosphor imaging	ic50	0.0100	uM
(E)-but-2-enedioic acid;N-[4-[5-[2-hydroxyethyl(methyl)amino]pentyl]cyclohexyl]-N-methyl-4-(trifluoromethyl)benzenesulfonamide	699374: Inhibition of human liver microsome 2,3-OSC after 1 hr by Silica gel plate phosphor imaging	ic50	0.0112	uM
(4-chlorophenyl) N-methyl-N-[4-[4-(piperidin-1-ylmethyl)phenyl]cyclohexyl]carbamate	151650: Inhibitory activity against Oxidosqualene-lanosterol cyclase from human liver microsomes	ic50	0.0113	uM
6-[[4-(4-bromophenyl)-2H-chromen-7-yl]oxy]-N-methyl-N-prop-2-enylhexan-1-amine	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0114	uM
6-[4-(4-bromophenyl)quinazolin-7-yl]oxy-N-methyl-N-prop-2-enylhexan-1-amine	298048: Inhibition of oxidosqualene cyclase	ic50	0.0123	uM
6-[4-(4-bromophenyl)quinazolin-7-yl]oxy-N-methyl-N-prop-2-enylhexan-1-amine;(E)-but-2-enedioic acid	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0123	uM
2-hydroxypropane-1,2,3-tricarboxylic acid;[4-(trifluoromethyl)phenyl] N-[2-[4-[[ethyl(2-hydroxyethyl)amino]methyl]cyclohexyl]ethyl]-N-methylcarbamate	699374: Inhibition of human liver microsome 2,3-OSC after 1 hr by Silica gel plate phosphor imaging	ic50	0.0127	uM
1-(4-chlorophenyl)sulfonyl-4-[(4-pyridin-4-ylphenyl)methyl]piperazine	408086: Inhibition of 2,3-oxidosqualene-lanosterol cyclase	ic50	0.0130	uM
(E)-4-[[3-(4-bromophenyl)-1-benzothiophen-6-yl]oxy]-N-methyl-N-prop-2-enylbut-2-en-1-amine	151650: Inhibitory activity against Oxidosqualene-lanosterol cyclase from human liver microsomes	ic50	0.0135	uM
(4-bromophenyl)-[4-[6-[3-hydroxypropyl(methyl)amino]hexoxy]phenyl]methanone;(E)-but-2-enedioic acid	2979: In vitro inhibition of human 2,3-oxidosqualene cyclase.	ic50	0.0157	uM
(4-bromophenyl)-[4-[6-[3-hydroxypropyl(methyl)amino]hexoxy]phenyl]methanone	298048: Inhibition of oxidosqualene cyclase	ic50	0.0158	uM
4-chloro-N-methyl-N-[1-[4-[[methyl(prop-2-enyl)amino]methyl]phenyl]piperidin-4-yl]benzenesulfonamide;dihydrochloride	1375929: Inhibition of human C-terminal His6-tagged OSC expressed in Pichia pastoris GS115 using 2,3-oxidosqualene as substrate after 90 mins by 1H NMR method	ic50	0.0160	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	6
Aflatoxin B1	affects expression, decreases expression, decreases methylation	6
bisphenol A	affects expression, decreases expression, increases expression	4
sodium arsenite	increases expression, affects expression, decreases expression, affects cotreatment, increases abundance	4
perfluorooctane sulfonic acid	decreases expression	4
Amiodarone	affects expression, increases expression	3
Amitriptyline	increases expression	3
Clozapine	increases expression, affects cotreatment, decreases expression	3
Fluoxetine	increases expression	3
Ketoconazole	increases expression	3
Tamoxifen	decreases expression, increases expression	3
Tobacco Smoke Pollution	decreases expression, increases methylation	3
Cyclosporine	affects cotreatment, affects expression, decreases expression	3
cobaltous chloride	decreases expression	2
perfluorooctanoic acid	decreases expression	2
tebuconazole	increases expression	2
Arsenic	decreases ubiquitination, affects cotreatment, decreases expression, increases abundance	2
trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride	increases expression	2
Chlorpromazine	increases expression	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Imipramine	increases expression	2
Nickel	decreases expression	2
Perhexiline	increases expression	2
Progesterone	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression, affects expression	2
Thioridazine	increases expression	2
beta-Naphthoflavone	affects reaction, decreases expression	2
Sertraline	increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	increases expression	1

ChEMBL screening assays

46 unique, capped per target: 45 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1036573	Binding	Inhibition of human OSC expressed in Saccharomyces cerevisiae SMY8	Oxidosqualene cyclase from Saccharomyces cerevisiae, Trypanosoma cruzi, Pneumocystis carinii and Arabidopsis thaliana expressed in yeast: a model for the development of novel antiparasitic agents. — Bioorg Med Chem Lett
CHEMBL758677	Functional	Tested for Oxidosqualene-lanosterol cyclase inhibition in Trypanosoma cruzi	Oxidosqualene cyclase inhibitors as antimicrobial agents. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03492866	PHASE2	UNKNOWN	Efficacy of Topical Gentamycin for Hereditary Hypotrichosis Simplex Caused by Nonsense Mutations in CDSN
NCT06068348	Not specified	ACTIVE_NOT_RECRUITING	Liquid Biopsy Collection Study