UGCG

Summary

UGCG (UDP-glucose ceramide glucosyltransferase, HGNC:12524) is a protein-coding gene on chromosome 9q31.3, encoding Ceramide glucosyltransferase (Q16739). Participates in the initial step of the glucosylceramide-based glycosphingolipid/GSL synthetic pathway at the cytosolic surface of the Golgi.

This gene encodes an enzyme that catalyzes the first glycosylation step in the biosynthesis of glycosphingolipids, which are membrane components containing lipid and sugar moieties. The product of this reaction is glucosylceramide, which is the core structure of many glycosphingolipids.

Source: NCBI Gene 7357 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ichthyosis (Limited, GenCC)
• GWAS associations: 7
• Clinical variants (ClinVar): 36 total
• Phenotypes (HPO): 1
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003358

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12524
Approved symbol	UGCG
Name	UDP-glucose ceramide glucosyltransferase
Location	9q31.3
Locus type	gene with protein product
Status	Approved
Aliases	GCS
Ensembl gene	ENSG00000148154
Ensembl biotype	protein_coding
OMIM	602874
Entrez	7357

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000374279, ENST00000474306, ENST00000489355, ENST00000490110, ENST00000495085, ENST00000856545, ENST00000856546, ENST00000915623, ENST00000940888

RefSeq mRNA: 1 — MANE Select: NM_003358 NM_003358

CCDS: CCDS6782

Canonical transcript exons

ENST00000374279 — 9 exons

Exon	Start	End
ENSE00000983456	111929500	111929678
ENSE00000983457	111931271	111931357
ENSE00000983458	111932170	111932359
ENSE00001462997	111932827	111935369
ENSE00001463003	111896814	111897313
ENSE00003582512	111922849	111922951
ENSE00003601488	111914605	111914746
ENSE00003636237	111926384	111926496
ENSE00003639730	111924777	111924878

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 98.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.3297 / max 5890.4247, expressed in 1823 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98022	43.6792	1814
98023	27.3768	1798
98027	0.2736	113

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	98.09	gold quality
bronchial epithelial cell	CL:0002328	97.83	gold quality
adrenal tissue	UBERON:0018303	97.78	gold quality
jejunal mucosa	UBERON:0000399	97.72	gold quality
vena cava	UBERON:0004087	97.32	gold quality
trabecular bone tissue	UBERON:0002483	97.00	gold quality
epithelium of nasopharynx	UBERON:0001951	96.95	gold quality
pericardium	UBERON:0002407	96.49	gold quality
cartilage tissue	UBERON:0002418	96.40	gold quality
buccal mucosa cell	CL:0002336	96.38	gold quality
bone marrow	UBERON:0002371	95.94	gold quality
oral cavity	UBERON:0000167	95.51	gold quality
lower esophagus mucosa	UBERON:0035834	95.43	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.07	gold quality
mammary duct	UBERON:0001765	94.73	gold quality
penis	UBERON:0000989	94.61	gold quality
nipple	UBERON:0002030	94.47	gold quality
esophagus squamous epithelium	UBERON:0006920	94.23	gold quality
lower lobe of lung	UBERON:0008949	94.23	gold quality
mammalian vulva	UBERON:0000997	94.22	gold quality
decidua	UBERON:0002450	94.20	gold quality
gall bladder	UBERON:0002110	94.19	gold quality
skin of hip	UBERON:0001554	94.18	gold quality
colonic mucosa	UBERON:0000317	94.12	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.12	gold quality
lymph node	UBERON:0000029	94.02	gold quality
pharyngeal mucosa	UBERON:0000355	93.52	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.37	gold quality
cauda epididymis	UBERON:0004360	93.35	gold quality
oocyte	CL:0000023	93.31	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 21.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	2917.25
E-GEOD-150728	yes	1487.85
E-CURD-122	yes	983.44
E-MTAB-9067	yes	698.63
E-HCAD-4	yes	61.30
E-HCAD-6	yes	36.37
E-MTAB-10287	yes	31.19
E-MTAB-6701	yes	27.41
E-GEOD-81547	yes	21.57
E-HCAD-1	yes	19.80
E-CURD-112	yes	18.22
E-CURD-119	yes	16.12
E-MTAB-9467	yes	15.62
E-MTAB-10042	yes	13.24
E-MTAB-6678	yes	12.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, FOS, GLI2, SP1

miRNA regulators (miRDB)

208 targeting UGCG, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4803	99.98	71.99	3117
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787

Literature-anchored findings (GeneRIF, showing 40)

• serve as negative regulator for ceramide (PMID:11915344)
• Glucosylceramide synthase and its functional interaction with RTN-1C regulate chemotherapeutic-induced apoptosis in neuroepithelioma cells. (PMID:12873973)
• inhibition of glucosylceramide synthase led to increased CER galactosylation and protected U937 and HL-60 cells from DNR-induced apoptosis (PMID:14766899)
• glucosylceramide synthase is not solely responsible for drug resistance in cancer cells (PMID:15263008)
• p-gp confers resistance to ceramide-induced apoptosis, with modulation of the ceramide-glucosylceramide pathway GCS making a marked contribution to this resistance (PMID:15661399)
• 10 genes were down-regulated following treatment of the T-ALL cells with 0.15 and 1.5 microg/mL of metal ores at 72 h. Transferase activity, transferring glycol groups (PMID:15747776)
• the reticulon family member RTN-1C has been expressed and purified in Escherichia coli and its molecular structure has been analysed by fluorescence and Circular Dichroism spectroscopy (PMID:16500619)
• it is suggested that a high level of GCS in leukemia is possible contributed to multidrug resistance of leukemia cells. (PMID:17709137)
• Western analysis for glucosylceramide synthase showed a significant decrease in Alzheimer disease brain consistent with the hypothesis that enzyme dysfunction contributes to neuronal decay. (PMID:18155680)
• High glucosylceramide synthase is associated with breast cancer. (PMID:18560890)
• GCSshRNA could efficiently suppress GCS and MDR1 expression in vitro and in vivo and these findings may be used as one of the methods to reverse multidrug resistance in breast cancer (PMID:19693666)
• Positive correlation was detected between the expression of GCS and MDR1 mRNA in K562/A02 cells and MDR1 mRNA expression was down regulated after silencing the GCS gene expression. (PMID:20533270)
• study demonstrates, for the first time, that GCS upregulates MDR1 expression modulating drug resistance of cancer. GSLs, in particular globo series GSLs mediate gene expression of MDR1 through cSrc and beta-catenin signaling pathway (PMID:20540746)
• Data indicate that a high expression of glucosylceramide synthase (GCS) seemed to be an indicator of poor prognosis. (PMID:20843709)
• Data show that GCS silencing increased the levels of phosphorylated p53 and p53-responsive genes. (PMID:21278235)
• inhibition of the GCS gene affects the expression of MDR1 mRNA and P-gp function. (PMID:21380926)
• GlcT-1 is up-regulated at the mRNA and protein levels during the course of U937 differentiation, resulting in increased amounts of GlcCer. (PMID:21558327)
• GCS overexpression was highly associated with ER-positive and HER2-positive breast cancer with metastasis. (PMID:21617856)
• Data show that nilotinib induces apoptosis through upregulating ceramide synthase genes and downregulating SK-1 in CML cells in addition to inhibition of BCR/ABL. (PMID:21756066)
• The authors conclude that hepatitis C virus proteins, especially NS5A and NS5B, have positive effects on the expression of human GlcT-1. (PMID:22270805)
• Ceramide glycosylation catalyzed by glucosylceramide synthase is important for cancer stem cells in drug resistance and tumorigenesis. (PMID:22936806)
• DOX could modulate the expression of GCS through the Sp1 site of GCS promoter in ERalpha-positive breast cancer cells (PMID:23133636)
• The results thus show that ARF6 regulates neuronal differentiation through an effect on glucosylceramide synthase and glucosylceramide levels. (PMID:23555901)
• our work indicates that some UGCG polymorphisms are modifying factors in the severity of GD. (PMID:23913449)
• GCS was upregulated in PTCs and might be an independent factor affecting prognosis. (PMID:24342307)
• Our data demonstrates a correlation between the expression of the GCS protein and ER-positive/HER-2 negative breast cancer (PMID:24456584)
• Glucosylceramide synthase mRNA were reduced by 62%. (PMID:24510559)
• We found upregulation of specific sphingolipid enzymes, namely sphingomyelin synthase 1 (SMS1), sphingomyelinase 3 (SMPD3), and glucosylceramide synthase (GCS) in the endometrium of endometriotic women. (PMID:24960545)
• GCS was upregulated in colorectal carcinoma tissues compared to control tissues. (PMID:25535133)
• Glucosylceramide synthase upregulation is associated with sorafenib resistance in hepatocellular carcinoma. (PMID:26811497)
• Results suggest that the changes of DNA methylation status of the glucosylceramide synthase (GCS) promoter correlates with multidrug resistance in breast cancer. (PMID:27191984)
• Studies show a connection between UDP-glucose ceramide glucosyltransferase (UGCG) and multidrug resistance protein 1 (MDR1) overexpression and multidrug resistance development [Review]. (PMID:29409484)
• the GCS inhibitor lucerastat provides a viable mechanism to reduce Gb3 accumulation and lysosome volume, suitable for all Fabry patients regardless of genotype (PMID:29982630)
• findings suggest that complex formation between SMS1 and GCS is part of a critical mechanism controlling the metabolic fate of Cer in the Golgi. (PMID:30242129)
• UGCG influences glutamine metabolism of breast cancer cells. (PMID:31666638)
• UGCG overexpression leads to increased glycolysis and increased oxidative phosphorylation of breast cancer cells. (PMID:32424263)
• Tyrosine-phosphorylation and activation of glucosylceramide synthase by v-Src: Its role in survival of HeLa cells against ceramide. (PMID:32980536)
• beta-Sitosterol 3-O-D-glucoside increases ceramide levels in the stratum corneum via the up-regulated expression of ceramide synthase-3 and glucosylceramide synthase in a reconstructed human epidermal keratinization model. (PMID:33684145)
• UDP-Glucose Ceramide Glycosyltransferase Contributes to the Proliferation and Glycolysis of Cervical Cancer Cells by Regulating the PI3K/AKT Pathway. (PMID:34686508)
• Glucosylceramide in T cells regulates the pathology of inflammatory bowel disease. (PMID:35168060)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	ugcg	ENSDARG00000058221
mus_musculus	Ugcg	ENSMUSG00000028381
rattus_norvegicus	Ugcg	ENSRNOG00000015644
drosophila_melanogaster	GlcT	FBGN0067102
caenorhabditis_elegans		WBGENE00011517
caenorhabditis_elegans		WBGENE00017625
caenorhabditis_elegans		WBGENE00019127

Protein

Protein identifiers

Ceramide glucosyltransferase — Q16739 (reviewed: Q16739)

Alternative names: GLCT-1, Glucosylceramide synthase, Glycosylceramide synthase, UDP-glucose ceramide glucosyltransferase, UDP-glucose:N-acylsphingosine D-glucosyltransferase

All UniProt accessions (1): Q16739

UniProt curated annotations — full annotation on UniProt →

Function. Participates in the initial step of the glucosylceramide-based glycosphingolipid/GSL synthetic pathway at the cytosolic surface of the Golgi. Catalyzes the transfer of glucose from UDP-glucose to ceramide to produce glucosylceramide/GlcCer (such as beta-D-glucosyl-(1<->1’)-N-acylsphing-4-enine). GlcCer is the core component of glycosphingolipids/GSLs, amphipathic molecules consisting of a ceramide lipid moiety embedded in the outer leaflet of the membrane, linked to one of hundreds of different externally oriented oligosaccharide structures. Glycosphingolipids are essential components of membrane microdomains that mediate membrane trafficking and signal transduction, implicated in many fundamental cellular processes, including growth, differentiation, migration, morphogenesis, cell-to-cell and cell-to-matrix interactions. They are required for instance in the proper development and functioning of the nervous system. As an example of their role in signal transduction, they regulate the leptin receptor/LEPR in the leptin-mediated signaling pathway. They also play an important role in the establishment of the skin barrier regulating keratinocyte differentiation and the proper assembly of the cornified envelope. The biosynthesis of GSLs is also required for the proper intestinal endocytic uptake of nutritional lipids. Catalyzes the synthesis of xylosylceramide/XylCer (such as beta-D-xylosyl-(1<->1’)-N-acylsphing-4-enine) using UDP-Xyl as xylose donor.

Subunit / interactions. Interacts with RTN1; regulates the ceramide glucosyltransferase activity of UGCG.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Found in all tissues examined.

Domain organisation. The D1, D2, D3, (Q/R)XXRW motif is a critical part of the GCS active site, involved in catalysis and UDP-sugar binding.

Pathway. Lipid metabolism; sphingolipid metabolism.

Similarity. Belongs to the glycosyltransferase 2 family.

RefSeq proteins (1): NP_003349* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025993	Ceramide_glucosylTrfase	Family
IPR029044	Nucleotide-diphossugar_trans	Homologous_superfamily

Pfam: PF13506

Enzyme classification (BRENDA):

• EC 2.4.1.80 — ceramide glucosyltransferase (BRENDA: 21 organisms, 58 substrates, 244 inhibitors, 13 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
UDP-GLUCOSE	0.0069–0.2	6
CERAMIDE	0.054–0.292	3
N-(6-((4-NITROBENZ-2-OXA-1,3-DIAZOL-7-YL)AMINO)C	0.013–0.02	2
C6-CERAMIDE	0.0406	1
NBD C6-CERAMIDE	0.0388	1

Catalyzed reactions (Rhea), 3 shown:

• an N-acylsphing-4-enine + UDP-alpha-D-glucose = a beta-D-glucosyl-(1<->1’)-N-acylsphing-4-enine + UDP + H(+) (RHEA:12088)
• UDP-alpha-D-xylose + an N-acylsphing-4-enine = a beta-D-xylosyl-(1<->1’)-N-acylsphing-4-enine + UDP + H(+) (RHEA:70243)
• N-(9Z-octadecenoyl)-sphing-4-enine + UDP-alpha-D-xylose = beta-D-xylosyl-(1<->1’)-N-(9Z-octadecenoyl)-sphing-4-enine + UDP + H(+) (RHEA:70247)

UniProt features (19 total): topological domain 6, transmembrane region 5, short sequence motif 4, chain 1, active site 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16739-F1	93.29	0.84

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 (2): 236 (proton acceptor); 193 (may play an important role in binding to the inhibitors depc and pdmp)

Post-translational modifications (1): 117

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9840309	Glycosphingolipid biosynthesis
R-HSA-1430728	Metabolism
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 414 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_DIGESTION, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_EPITHELIUM_DEVELOPMENT, YANG_BREAST_CANCER_ESR1_LASER_UP, MODULE_255, GOBP_RESPONSE_TO_PEPTIDE, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, GOBP_MEMBRANE_BIOGENESIS, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, AMIT_EGF_RESPONSE_60_HELA, GOZGIT_ESR1_TARGETS_DN, HALMOS_CEBPA_TARGETS_UP

GO Biological Process (14): protein lipidation (GO:0006497), glucosylceramide biosynthetic process (GO:0006679), glycosphingolipid biosynthetic process (GO:0006688), epidermis development (GO:0008544), regulation of signal transduction (GO:0009966), cell differentiation (GO:0030154), keratinocyte differentiation (GO:0030216), leptin-mediated signaling pathway (GO:0033210), neuron development (GO:0048666), establishment of skin barrier (GO:0061436), intestinal lipid absorption (GO:0098856), cornified envelope assembly (GO:1903575), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665)

GO Molecular Function (4): ceramide glucosyltransferase activity (GO:0008120), protein binding (GO:0005515), transferase activity (GO:0016740), glycosyltransferase activity (GO:0016757)

GO Cellular Component (3): Golgi membrane (GO:0000139), membrane (GO:0016020), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Glycosphingolipid metabolism	1
Sphingolipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein modification process	1
lipoprotein biosynthetic process	1
glucosylceramide metabolic process	1
glycosphingolipid biosynthetic process	1
ceramide biosynthetic process	1
glycosphingolipid metabolic process	1
glycolipid biosynthetic process	1
sphingolipid biosynthetic process	1
tissue development	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
cellular developmental process	1
epidermal cell differentiation	1
skin development	1
cytokine-mediated signaling pathway	1
cellular response to leptin stimulus	1
neuron differentiation	1
cell development	1
skin epidermis development	1
intestinal absorption	1
protein-glutamine gamma-glutamyltransferase activity	1
plasma membrane organization	1
membrane assembly	1
primary metabolic process	1
lipid metabolic process	1
UDP-glucosyltransferase activity	1
binding	1
catalytic activity	1
transferase activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1896 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UGCG	GBA1	P04062	928
UGCG	CHIT1	Q13231	923
UGCG	B4GALT6	Q9UBX8	858
UGCG	SPTLC1	O15269	845
UGCG	SPTLC2	O15270	825
UGCG	SPTLC3	Q9NUV7	822
UGCG	CERK	Q8TCT0	783
UGCG	GBA2	Q9HCG7	763
UGCG	SMPD2	O60906	744
UGCG	B4GALT5	O43286	741
UGCG	DEGS1	O15121	732
UGCG	ASAH1	Q13510	730
UGCG	CERS6	Q6ZMG9	726
UGCG	CERS2	Q96G23	716
UGCG	SMPD1	P17405	711

IntAct

42 interactions, top by confidence:

A	B	Type	Score
SLC20A1	LIN7A	psi-mi:“MI:0914”(association)	0.640
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
TSPAN3	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.530
CD83	BTAF1	psi-mi:“MI:0914”(association)	0.530
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
MRAP2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
UGCG	RTN1	psi-mi:“MI:0915”(physical association)	0.370
CHMP4B	ELOC	psi-mi:“MI:0914”(association)	0.350
LMP2	WWP2	psi-mi:“MI:0914”(association)	0.350
TNFRSF10A	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
RUSF1	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
SLC20A1	MPP2	psi-mi:“MI:0914”(association)	0.350
MRAP2	GOSR1	psi-mi:“MI:0914”(association)	0.350
HEPACAM2	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
TMEM231	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
TNFRSF10B	SCAMP1	psi-mi:“MI:0914”(association)	0.350
PTGIR	GPAA1	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
KCNK18	TMEM223	psi-mi:“MI:0914”(association)	0.350
CRLF2	METTL15	psi-mi:“MI:0914”(association)	0.350
CX3CL1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
EDAR	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
TMEM59	GPR89A	psi-mi:“MI:0914”(association)	0.350
KCNE3	PIK3R2	psi-mi:“MI:0914”(association)	0.350
HEPACAM2	PIK3R2	psi-mi:“MI:0914”(association)	0.350
TNFRSF10A	SDCBP	psi-mi:“MI:0914”(association)	0.350
CD83	ABCD4	psi-mi:“MI:0914”(association)	0.350

BioGRID (60): UGCG (Affinity Capture-MS), UGCG (Affinity Capture-MS), UGCG (Affinity Capture-MS), UGCG (Affinity Capture-MS), UGCG (Affinity Capture-MS), UGCG (Affinity Capture-MS), RTN1 (Two-hybrid), UGCG (Affinity Capture-MS), UGCG (Affinity Capture-MS), UGCG (Affinity Capture-MS), UGCG (Affinity Capture-MS), UGCG (Affinity Capture-MS), UGCG (Affinity Capture-MS), UGCG (Affinity Capture-MS), UGCG (Affinity Capture-MS)

ESM2 similar proteins: A0A0E0S977, A0A8V0ZB02, A2Z1F5, A8XAC4, B1WB39, B8AIW3, C4R4B3, F7B909, G4MS28, G5EC84, O01346, O18037, O57428, O88693, P13563, Q03562, Q14849, Q16739, Q1LZ86, Q21054, Q3T0T0, Q3TWI9, Q4LE88, Q4R2Y9, Q52463, Q5BL38, Q5EA42, Q5T3F8, Q5U4S8, Q5XI64, Q61542, Q67WQ7, Q69PA8, Q6ETL8, Q6GLL2, Q6GML1, Q71B07, Q88NC5, Q8AY29, Q8H1Z0

Diamond homologs: A0A1U8QQU5, C4R4B3, G4MS28, I1RPI4, J9W453, O88693, Q16739, Q5AMQ4, Q5BL38, Q5U4S8, Q8AY29, G5EC84, O18037, Q21054, Q9R0E0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SP1	“up-regulates quantity by expression”	UGCG	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 56 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
transmembrane transport	5	19.1×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	22
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1154 predictions. Top by Δscore:

Variant	Effect	Δscore
9:111897311:CACGT:C	donor_loss	1.0000
9:111897313:CGT:C	donor_loss	1.0000
9:111897314:G:GG	donor_gain	1.0000
9:111897318:G:GG	donor_gain	1.0000
9:111914602:TAGCC:T	acceptor_loss	1.0000
9:111914603:A:AG	acceptor_gain	1.0000
9:111914603:AGCC:A	acceptor_gain	1.0000
9:111914604:G:GT	acceptor_gain	1.0000
9:111914604:GC:G	acceptor_gain	1.0000
9:111914604:GCC:G	acceptor_gain	1.0000
9:111914604:GCCG:G	acceptor_gain	1.0000
9:111914604:GCCGA:G	acceptor_gain	1.0000
9:111914742:CCAAA:C	donor_gain	1.0000
9:111914743:CAAA:C	donor_gain	1.0000
9:111914744:AAA:A	donor_gain	1.0000
9:111914744:AAAG:A	donor_loss	1.0000
9:111914745:AA:A	donor_gain	1.0000
9:111914745:AAG:A	donor_loss	1.0000
9:111914746:AGT:A	donor_loss	1.0000
9:111914747:G:GG	donor_gain	1.0000
9:111914747:GT:G	donor_loss	1.0000
9:111914748:T:A	donor_loss	1.0000
9:111914749:AA:A	donor_loss	1.0000
9:111914752:T:G	donor_gain	1.0000
9:111915837:G:GG	donor_gain	1.0000
9:111922847:A:AG	acceptor_gain	1.0000
9:111922848:G:GA	acceptor_gain	1.0000
9:111922848:GT:G	acceptor_gain	1.0000
9:111922848:GTAT:G	acceptor_gain	1.0000
9:111922951:GGT:G	donor_loss	1.0000

AlphaMissense

2601 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:111929648:A:C	D236A	1.000
9:111929648:A:T	D236V	1.000
9:111924864:A:T	D144V	0.999
9:111929647:G:C	D236H	0.999
9:111929648:A:G	D236G	0.999
9:111929649:T:A	D236E	0.999
9:111929649:T:G	D236E	0.999
9:111932171:T:A	W276R	0.999
9:111932171:T:C	W276R	0.999
9:111932173:G:C	W276C	0.999
9:111932173:G:T	W276C	0.999
9:111932869:T:A	W353R	0.999
9:111932869:T:C	W353R	0.999
9:111914677:A:C	K57N	0.998
9:111914677:A:T	K57N	0.998
9:111914715:T:C	L70P	0.998
9:111922864:T:C	C86R	0.998
9:111922866:T:G	C86W	0.998
9:111924799:T:A	N122K	0.998
9:111924799:T:G	N122K	0.998
9:111924804:A:T	K124I	0.998
9:111924805:A:C	K124N	0.998
9:111924805:A:T	K124N	0.998
9:111929645:A:T	E235V	0.998
9:111929647:G:T	D236Y	0.998
9:111931357:G:T	R275M	0.998
9:111932184:G:C	R280P	0.998
9:111932243:A:C	S300R	0.998
9:111932245:T:A	S300R	0.998
9:111932245:T:G	S300R	0.998

dbSNP variants (sampled 300 via entrez): RS1000189198 (9:111899154 A>T), RS1000361753 (9:111904516 C>T), RS1000418560 (9:111927664 G>T), RS1000455931 (9:111916040 T>C), RS1000557143 (9:111909847 C>A,T), RS1000646001 (9:111899427 A>G), RS1000653603 (9:111905471 T>TG), RS1000707184 (9:111899691 A>G), RS1000809131 (9:111932160 G>A,T), RS1000847756 (9:111915709 T>C), RS1000863087 (9:111932571 A>C), RS1000903331 (9:111904453 T>A), RS1000925522 (9:111933391 G>A), RS1001050733 (9:111927596 T>C), RS1001056993 (9:111895633 C>G)

Disease associations

OMIM: gene MIM:602874 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
ichthyosis	Limited	Autosomal recessive

Mondo (2): congenital non-bullous ichthyosiform erythroderma (MONDO:0019306), ichthyosis (MONDO:0019269)

Orphanet (1): Congenital ichthyosiform erythroderma (Orphanet:79394)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0007431	Congenital ichthyosiform erythroderma

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004621_129	Red cell distribution width	4.000000e-18
GCST006804_46	Red cell distribution width	3.000000e-13
GCST008169_10	Benign prostatic hyperplasia	2.000000e-06
GCST009391_1120	Metabolite levels	2.000000e-06
GCST90002390_395	Mean corpuscular hemoglobin	2.000000e-16
GCST90002403_615	Red blood cell count	8.000000e-16
GCST90002404_119	Red cell distribution width	5.000000e-44

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0010523	phosphoglyceric acid measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007057	Ichthyosis	C16.131.831.512; C16.614.492; C17.800.428.333; C17.800.804.512

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2063 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 5,614 (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
CHEMBL1029	MIGLUSTAT	4	4,770
CHEMBL2110588	ELIGLUSTAT	4	687
CHEMBL1086997	LUCERASTAT	3	74
CHEMBL4297611	VENGLUSTAT	3	76
CHEMBL3354637	NIZUBAGLUSTAT	2	7

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Ceramide glucosyltransferase

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
nizubaglustat	Inhibition	8.6	pIC50
T-690	Inhibition	7.82	pIC50
venglustat	Inhibition	5.3	pIC50
miglustat	Inhibition	5.13	pKi

Binding affinities (BindingDB)

434 measured of 434 human assays (434 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(1-azabicyclo[2.2.2]octan-3-yl)-7-(2-butoxyphenyl)-1-benzofuran-2-carboxamide	EC50	0.021 nM	US-20230391758: MODIFIED BENZOFURAN-CARBOXAMIDES AS GLUCOSYLCERAMIDE SYNTHASE INHIBITORS
(S)-quinuclidin-3-yl (7-methoxy-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.19 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (7-fluoro-6-(4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.29 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (7-fluoro-6-(4-isobutylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.3 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (7-fluoro-2,2-dimethyl-6-(4-propylphenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.31 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (7-fluoro-6-(3-fluoro-4-methoxyphenyll)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.5 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(4-isobutylphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.53 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(4-isopropoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.55 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6’-(4-propoxyphenyl)-3’,4’-dihydro-1’H-spiro[cyclopropane-1,2’-naphthalen]-1’-yl) carbamate	IC50	0.63 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(4-(2-methoxyethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.64 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(3-fluoro-4-methoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.65 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(3-chlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.697 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6’-(4-propylphenyl)-3’,4’-dihydro-1’H-spiro[cyclopropane-1,2’-naphthalen]-1’-yl)carbamate	IC50	0.75 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.81 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(3-fluoro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.83 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
N-[(1R,2R)-1-[4-(cyclopropylmethoxy)phenyl]-1-hydroxy-3-pyrrolidin-1-ylpropan-2-yl]-2-(2,3-dihydro-1H-inden-2-yl)acetamide	IC50	0.84 nM	US-10202340: Glucosylceramide synthase inhibitors and therapeutic methods using the same
(S)-quinuclidin-3-yl (6-(2-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.85 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (2,2-dimethyl-6-(2-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.86 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(2-(tert-butoxy)pyridin-4-yl)-(7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.86 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
2-(2,3-dihydro-1H-inden-2-yl)-N-[(1R,2R)-1-hydroxy-3-pyrrolidin-1-yl-1-[4-(2,2,2-trifluoroethoxy)phenyl]propan-2-yl]acetamide	IC50	0.87 nM	US-10202340: Glucosylceramide synthase inhibitors and therapeutic methods using the same
(S)-quinuclidin-3-yl (6-(3-fluoro-4-propoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.87 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6’-(4-cyclopropylphenyl)-3’,4’-dihydro-1’H-spiro[cyclopropane-1,2’-naphthalen]-1’-yl)carbamate	IC50	0.93 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(4-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.94 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(2,5-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.95 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(2-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.97 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(2-chloro-4-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.97 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(3-fluorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	0.989 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(2,3-difluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(4-butoxy-3,5-dimethylphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.01 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6’-(4-ethoxyphenyl)-3’,4’-dihydro-1’H-spiro[cyclopropane-1,2’-naphthalen]-1’-yl)carbamate	IC50	1.01 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6’-(4-(2-methoxyethoxy)phenyl)-3’,4’-dihydro-1’H-spiro[cyclopropane-1,2’-naphthalen]-1’-yl)carbamate	IC50	1.03 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (2,2-dimethyl-6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.04 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(2,3-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.05 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(2-chloro-5-methoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.1 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6’-(4-isopropoxyphenyl)-3’,4’-dihydro-1’H-spiro[cyclopropane-1,2’-naphthalen]-1’-yl)carbamate	IC50	1.1 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(3-fluoro-4-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.11 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(3-isopropoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.16 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6’-(3-fluoro-4-methoxyphenyl)-3’,4’-dihydro-1’H-spiro[cyclopropane-1,2’-naphthalen]-1’-yl)carbamate	IC50	1.16 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(2-(methoxymethoxy)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.17 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(3,5-dimethoxyphenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.19 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(3-(difluoromethyl)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.24 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(3-(methoxymethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.33 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(3,5-dimethyl-4-propoxyphenyl)-(7-fluoro-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.34 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(2,5-dichlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.39 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(4-ethoxy-3-fluorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.39 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(4-(trifluoromethoxy)phenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.42 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(4-butoxy-3-chlorophenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.44 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(3,5-dimethyl-4-propoxyphenyl)-7-methoxy-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.45 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
(S)-quinuclidin-3-yl (6-(3-(dimethylamino)phenyl)-2,2-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)carbamate	IC50	1.49 nM	US-12338237: Derivatives having 1,2,3,4-tetrahydronaphthalene moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same

ChEMBL bioactivities

407 potent at pChembl≥5 of 418 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	EC50	0.02	nM	CHEMBL5182897
10.68	EC50	0.021	nM	CHEMBL5170109
10.64	EC50	0.023	nM	CHEMBL5191157
10.36	EC50	0.044	nM	CHEMBL5177098
10.36	EC50	0.044	nM	CHEMBL5195638
10.33	EC50	0.047	nM	CHEMBL5197108
10.00	EC50	0.1	nM	CHEMBL5415069
10.00	EC50	0.1	nM	CHEMBL5414358
10.00	EC50	0.1	nM	CHEMBL5418636
10.00	EC50	0.1	nM	CHEMBL5286071
10.00	EC50	0.1	nM	CHEMBL5413252
10.00	EC50	0.1	nM	CHEMBL5426863
9.70	EC50	0.2	nM	CHEMBL5408662
9.70	EC50	0.2	nM	CHEMBL5395933
9.52	EC50	0.3	nM	CHEMBL5398714
9.52	EC50	0.3	nM	CHEMBL5431661
9.52	IC50	0.3	nM	CHEMBL1911818
9.40	EC50	0.4	nM	CHEMBL5420341
9.08	IC50	0.84	nM	CHEMBL5842505
9.06	IC50	0.87	nM	CHEMBL5969221
9.05	IC50	0.9	nM	CHEMBL5415209
9.05	EC50	0.9	nM	CHEMBL5406074
9.00	IC50	1	nM	CHEMBL5290844
9.00	IC50	1	nM	CHEMBL5842505
9.00	IC50	1	nM	CHEMBL1911818
9.00	IC50	1	nM	CHEMBL1911817
8.77	IC50	1.7	nM	CHEMBL5275403
8.74	IC50	1.8	nM	CHEMBL5425600
8.70	IC50	2	nM	CHEMBL2163821
8.70	IC50	2	nM	CHEMBL1911679
8.70	IC50	2	nM	CHEMBL1911678
8.70	IC50	2	nM	CHEMBL2163825
8.70	IC50	2	nM	CHEMBL2163828
8.70	IC50	2	nM	CHEMBL2163838
8.70	IC50	2	nM	CHEMBL1911816
8.70	IC50	2	nM	CHEMBL1911815
8.70	IC50	2	nM	CHEMBL1911817
8.68	IC50	2.1	nM	CHEMBL5411678
8.60	IC50	2.5	nM	NIZUBAGLUSTAT
8.60	IC50	2.5	nM	CHEMBL5969221
8.59	IC50	2.6	nM	CHEMBL5425600
8.52	IC50	3	nM	CHEMBL2163833
8.52	IC50	3	nM	CHEMBL2163827
8.52	IC50	3	nM	CHEMBL2163826
8.52	IC50	3	nM	CHEMBL2163823
8.52	IC50	3	nM	CHEMBL3354022
8.52	IC50	3	nM	CHEMBL3354024
8.52	IC50	3	nM	CHEMBL3354035
8.52	IC50	3	nM	CHEMBL3354037
8.52	IC50	3	nM	CHEMBL3354634

PubChem BioAssay actives

262 with measured affinity, of 331 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
N-(1-azabicyclo[2.2.2]octan-3-yl)-5-chloro-7-[2-(2-fluoroethoxy)phenyl]-1-benzofuran-2-carboxamide	1880839: Inhibition of GCS in human A-375 cells using C6-ceramide and UDP-glucose as substrate preincubated for 30 mins followed by substrate addition measured after 20 hrs by UDP-Glo glucosylceramide synthase based luminometer analysis	ec50	<0.0001	uM
N-(1,6-naphthyridin-2-yl)-7-[2-(2,2,2-trifluoroethoxy)phenyl]-1-benzofuran-2-carboxamide	1880839: Inhibition of GCS in human A-375 cells using C6-ceramide and UDP-glucose as substrate preincubated for 30 mins followed by substrate addition measured after 20 hrs by UDP-Glo glucosylceramide synthase based luminometer analysis	ec50	<0.0001	uM
5-chloro-7-(5-cyano-2-propan-2-yloxyphenyl)-N-(3-hydroxycyclobutyl)-1-benzofuran-2-carboxamide	1880839: Inhibition of GCS in human A-375 cells using C6-ceramide and UDP-glucose as substrate preincubated for 30 mins followed by substrate addition measured after 20 hrs by UDP-Glo glucosylceramide synthase based luminometer analysis	ec50	<0.0001	uM
N-(1-azabicyclo[2.2.2]octan-3-yl)-7-(2-propoxyphenyl)-1-benzofuran-2-carboxamide	1880839: Inhibition of GCS in human A-375 cells using C6-ceramide and UDP-glucose as substrate preincubated for 30 mins followed by substrate addition measured after 20 hrs by UDP-Glo glucosylceramide synthase based luminometer analysis	ec50	<0.0001	uM
N-(1-azabicyclo[2.2.2]octan-3-yl)-7-(2-butoxyphenyl)-1-benzofuran-2-carboxamide	1880839: Inhibition of GCS in human A-375 cells using C6-ceramide and UDP-glucose as substrate preincubated for 30 mins followed by substrate addition measured after 20 hrs by UDP-Glo glucosylceramide synthase based luminometer analysis	ec50	<0.0001	uM
7-(2-chloro-5-cyanophenyl)-N-[(1S,3R)-3-hydroxycyclopentyl]-1-benzofuran-2-carboxamide	1880839: Inhibition of GCS in human A-375 cells using C6-ceramide and UDP-glucose as substrate preincubated for 30 mins followed by substrate addition measured after 20 hrs by UDP-Glo glucosylceramide synthase based luminometer analysis	ec50	<0.0001	uM
1,4-diazabicyclo[3.2.2]nonan-4-yl-[9-(4-fluorophenyl)-7,8-diazatricyclo[4.3.0.02,4]nona-1(6),8-dien-7-yl]methanone	2011701: Inhibition of GCS in human A-375 cell golgi body using C6-ceramide and UDP-glucose as substrate assessed as reduction in UDP production preincubated for 30 mins followed by substrate addition and measured after 20 hrs by UDP-Glo luminometer analysis	ec50	0.0001	uM
[(2S,4S)-7-(5-chloro-6-methoxy-3-pyridinyl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-dien-9-yl]-(1,4-diazabicyclo[3.2.2]nonan-4-yl)methanone	2011701: Inhibition of GCS in human A-375 cell golgi body using C6-ceramide and UDP-glucose as substrate assessed as reduction in UDP production preincubated for 30 mins followed by substrate addition and measured after 20 hrs by UDP-Glo luminometer analysis	ec50	0.0001	uM
1,4-diazabicyclo[3.2.2]nonan-4-yl-[(2S,4S)-7-[4-(trifluoromethyl)pyrazol-1-yl]-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-dien-9-yl]methanone	2011701: Inhibition of GCS in human A-375 cell golgi body using C6-ceramide and UDP-glucose as substrate assessed as reduction in UDP production preincubated for 30 mins followed by substrate addition and measured after 20 hrs by UDP-Glo luminometer analysis	ec50	0.0001	uM
1,4-diazabicyclo[3.2.2]nonan-4-yl-[1-[4-methoxy-3-(trifluoromethyl)phenyl]-5,6-dihydro-4H-cyclopenta[d]pyrazol-3-yl]methanone	2038985: Inhibition of GCS activity in human A-375 cells using C6 ceramide as substrate pre-incubated for 30 mins followed by substrate addition and measured after 20 hrs by UDP-Glo based luminometric analysis	ec50	0.0001	uM
1,4-diazabicyclo[3.2.2]nonan-4-yl-[1-(3,4-dichlorophenyl)-5,6-dihydro-4H-cyclopenta[d]pyrazol-3-yl]methanone	2038985: Inhibition of GCS activity in human A-375 cells using C6 ceramide as substrate pre-incubated for 30 mins followed by substrate addition and measured after 20 hrs by UDP-Glo based luminometric analysis	ec50	0.0001	uM
1,4-diazabicyclo[3.2.2]nonan-4-yl-[(2S,4S)-7-(4-fluorophenyl)-8,9-diazatricyclo[4.3.0.02,4]nona-1(6),7-dien-9-yl]methanone	2011701: Inhibition of GCS in human A-375 cell golgi body using C6-ceramide and UDP-glucose as substrate assessed as reduction in UDP production preincubated for 30 mins followed by substrate addition and measured after 20 hrs by UDP-Glo luminometer analysis	ec50	0.0001	uM
1,4-diazabicyclo[3.2.2]nonan-4-yl-[3-(4-methoxyphenyl)-5,6-dihydro-4H-cyclopenta[d]pyrazol-1-yl]methanone	2011701: Inhibition of GCS in human A-375 cell golgi body using C6-ceramide and UDP-glucose as substrate assessed as reduction in UDP production preincubated for 30 mins followed by substrate addition and measured after 20 hrs by UDP-Glo luminometer analysis	ec50	0.0002	uM
1,4-diazabicyclo[3.2.2]nonan-4-yl-[3-(4-methylphenyl)-5,6-dihydro-4H-cyclopenta[d]pyrazol-1-yl]methanone	2011701: Inhibition of GCS in human A-375 cell golgi body using C6-ceramide and UDP-glucose as substrate assessed as reduction in UDP production preincubated for 30 mins followed by substrate addition and measured after 20 hrs by UDP-Glo luminometer analysis	ec50	0.0002	uM
[1-(3-chloro-4-methylphenyl)-5,6-dihydro-4H-cyclopenta[d]pyrazol-3-yl]-(1,4-diazabicyclo[3.2.2]nonan-4-yl)methanone	2038985: Inhibition of GCS activity in human A-375 cells using C6 ceramide as substrate pre-incubated for 30 mins followed by substrate addition and measured after 20 hrs by UDP-Glo based luminometric analysis	ec50	0.0003	uM
[1-(3-chloro-4-methoxyphenyl)-5,6-dihydro-4H-cyclopenta[d]pyrazol-3-yl]-(1,4-diazabicyclo[3.2.2]nonan-4-yl)methanone	2038985: Inhibition of GCS activity in human A-375 cells using C6 ceramide as substrate pre-incubated for 30 mins followed by substrate addition and measured after 20 hrs by UDP-Glo based luminometric analysis	ec50	0.0003	uM
2-[2-chloro-4-(trifluoromethyl)phenoxy]-N-[(2R)-3-(2,3-dihydro-1,4-benzodioxin-6-ylmethoxy)-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl]pyridine-3-carboxamide	626356: Inhibition of GCS activity in human A549 cells assessed as amount of GM1 on the cell membrane after 72 hrs by FL-CTB-based fluorescent microscopy	ic50	0.0003	uM
1,4-diazabicyclo[3.2.2]nonan-4-yl-[1-(4-methoxy-3-methylphenyl)-5,6-dihydro-4H-cyclopenta[d]pyrazol-3-yl]methanone	2038985: Inhibition of GCS activity in human A-375 cells using C6 ceramide as substrate pre-incubated for 30 mins followed by substrate addition and measured after 20 hrs by UDP-Glo based luminometric analysis	ec50	0.0004	uM
2-[(1R)-1-cyclopropyl-2-hydroxy-2-methylpropyl]-5,6-difluoro-7-[4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]-3H-isoindol-1-one	2005894: Inhibition of GCS in human A-375 cell golgi body preparations using ceramide and UDP-glucose as substrate by UDP-Glo based luminometric analysis	ic50	0.0009	uM
1,4-diazabicyclo[3.2.2]nonan-4-yl-[1-(3-fluoro-4-methoxyphenyl)-5,6-dihydro-4H-cyclopenta[d]pyrazol-3-yl]methanone	2038985: Inhibition of GCS activity in human A-375 cells using C6 ceramide as substrate pre-incubated for 30 mins followed by substrate addition and measured after 20 hrs by UDP-Glo based luminometric analysis	ec50	0.0009	uM
[3-(3-chloro-4-fluorophenyl)-5,7-dihydro-4H-pyrano[4,3-d]pyrazol-1-yl]-(1,4-diazabicyclo[3.2.2]nonan-4-yl)methanone	1923000: Inhibition of Glucosylceramide synthase (unknown origin) using C6-ceramide and UDP-glucose as substrate preincubated for 30 mins followed by substrate addition and measured after 2 hrs by UDP-Glo luminometer analysis	ic50	0.0010	uM
2-[2-chloro-4-(trifluoromethyl)phenoxy]-N-[(2R)-1-(4-methylpiperazin-1-yl)-1-oxo-3-phenylmethoxypropan-2-yl]pyridine-3-carboxamide	626355: Inhibition of GCS assessed as amount of UDP-glucose consumed during enzyme-catalyzed reaction	ic50	0.0010	uM
1,4-diazabicyclo[3.2.2]nonan-4-yl-[3-[4-(trifluoromethyl)pyrazol-1-yl]-5,7-dihydro-4H-pyrano[4,3-d]pyrazol-1-yl]methanone;hydrochloride	1923042: Inhibition of GCS in human iPSC derived neurons assessed as reduction in brain GlcCer levels	ic50	0.0017	uM
2-[(1R)-1-cyclopropyl-2-hydroxy-2-methylpropyl]-6-fluoro-7-[4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]-3H-isoindol-1-one	2005895: Inhibition of GCS in wild type HDF cells by LC-MS assay	ic50	0.0018	uM
2-(2,4-dichlorophenoxy)-N-[(2R)-1-(4-methylpiperazin-1-yl)-1-oxo-3-phenylmethoxypropan-2-yl]pyridine-3-carboxamide	626355: Inhibition of GCS assessed as amount of UDP-glucose consumed during enzyme-catalyzed reaction	ic50	0.0020	uM
N-[(1R,2S)-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-hydroxy-3-pyrrolidin-1-ylpropan-2-yl]octanamide	626356: Inhibition of GCS activity in human A549 cells assessed as amount of GM1 on the cell membrane after 72 hrs by FL-CTB-based fluorescent microscopy	ic50	0.0020	uM
2-(4-chloro-2-methylphenoxy)-N-[(2R)-1-(4-methylpiperazin-1-yl)-1-oxo-3-phenylmethoxypropan-2-yl]pyridine-3-carboxamide	626355: Inhibition of GCS assessed as amount of UDP-glucose consumed during enzyme-catalyzed reaction	ic50	0.0020	uM
N-[(1R,2S)-1-(2,3-dihydro-1,4-benzodioxin-6-yl)-1-hydroxy-3-pyrrolidin-1-ylpropan-2-yl]nonanamide	626356: Inhibition of GCS activity in human A549 cells assessed as amount of GM1 on the cell membrane after 72 hrs by FL-CTB-based fluorescent microscopy	ic50	0.0020	uM
1-(2,4-dichlorophenyl)-N-[3-(1H-indol-3-yl)-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl]cyclopropane-1-carboxamide	699203: Inhibition of GCS assessed as amount of UDP glucose after 3 hrs by Fluorometry analysis	ic50	0.0020	uM
1-(2,4-dichlorophenyl)-N-[(2S)-3-(2,4-dichlorophenyl)-1-[2-(dimethylamino)ethyl-methylamino]-1-oxopropan-2-yl]cyclopropane-1-carboxamide	699203: Inhibition of GCS assessed as amount of UDP glucose after 3 hrs by Fluorometry analysis	ic50	0.0020	uM
N-[(2S)-1-[(1R,5S)-3-amino-8-azabicyclo[3.2.1]octan-8-yl]-3-(2,4-dichlorophenyl)-1-oxopropan-2-yl]-1-(2,4-dichlorophenyl)cyclopropane-1-carboxamide	699202: Inhibition of GCS in human A549 cells assessed as decrease in GM1 synthesis after 72 hrs by Fluorescence assay	ic50	0.0020	uM
N-[(2S)-1-[(1R,5S)-3-amino-8-azabicyclo[3.2.1]octan-8-yl]-3-(4-bromophenyl)-1-oxopropan-2-yl]-1-[4-(trifluoromethoxy)phenyl]cyclopropane-1-carboxamide	699203: Inhibition of GCS assessed as amount of UDP glucose after 3 hrs by Fluorometry analysis	ic50	0.0020	uM
2-[(1R)-1-cyclopropyl-2-hydroxy-2-methylpropyl]-5-fluoro-7-[4-(5-methyl-1,3,4-oxadiazol-2-yl)phenyl]-3H-isoindol-1-one	2005894: Inhibition of GCS in human A-375 cell golgi body preparations using ceramide and UDP-glucose as substrate by UDP-Glo based luminometric analysis	ic50	0.0021	uM
(2S,3R,4R,5S)-1-[5-[(3-fluoro-4-phenylphenyl)methoxy]pentyl]-2-(hydroxymethyl)piperidine-3,4,5-triol	1166037: Inhibition of glucosylceramide synthase (unknown origin) assessed as catabolism of NBD-glucosylceramide	ic50	0.0025	uM
(2S,3R,4R,5S)-2-(hydroxymethyl)-1-[5-[[4-phenyl-2-(trifluoromethyl)phenyl]methoxy]pentyl]piperidine-3,4,5-triol	1166037: Inhibition of glucosylceramide synthase (unknown origin) assessed as catabolism of NBD-glucosylceramide	ic50	0.0030	uM
(2S,3R,4R,5S)-2-(hydroxymethyl)-1-[5-[[4-phenyl-3-(trifluoromethyl)phenyl]methoxy]pentyl]piperidine-3,4,5-triol	1166037: Inhibition of glucosylceramide synthase (unknown origin) assessed as catabolism of NBD-glucosylceramide	ic50	0.0030	uM
(2R,3R,4R,5S)-2-(hydroxymethyl)-1-[5-(naphthalen-2-ylmethoxy)pentyl]piperidine-3,4,5-triol	1166037: Inhibition of glucosylceramide synthase (unknown origin) assessed as catabolism of NBD-glucosylceramide	ic50	0.0030	uM
(2R,3R,4R,5S)-2-(hydroxymethyl)-1-[5-(pyren-1-ylmethoxy)pentyl]piperidine-3,4,5-triol	1166037: Inhibition of glucosylceramide synthase (unknown origin) assessed as catabolism of NBD-glucosylceramide	ic50	0.0030	uM
(2S,3R,4R,5S)-2-(hydroxymethyl)-1-[5-(naphthalen-2-ylmethoxy)pentyl]piperidine-3,4,5-triol	1166037: Inhibition of glucosylceramide synthase (unknown origin) assessed as catabolism of NBD-glucosylceramide	ic50	0.0030	uM
(2S,3R,4R,5S)-2-(hydroxymethyl)-1-[5-(pyren-1-ylmethoxy)pentyl]piperidine-3,4,5-triol	1166037: Inhibition of glucosylceramide synthase (unknown origin) assessed as catabolism of NBD-glucosylceramide	ic50	0.0030	uM
2-(2,4-dichlorophenoxy)-5-fluoro-N-[(2R)-1-(4-methylpiperazin-1-yl)-1-oxo-3-phenylmethoxypropan-2-yl]pyridine-3-carboxamide	626355: Inhibition of GCS assessed as amount of UDP-glucose consumed during enzyme-catalyzed reaction	ic50	0.0030	uM
N-[(2S)-3-(4-chlorophenyl)-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl]-1-(2,4-dichlorophenyl)cyclopropane-1-carboxamide	699202: Inhibition of GCS in human A549 cells assessed as decrease in GM1 synthesis after 72 hrs by Fluorescence assay	ic50	0.0030	uM
N-[(2S)-1-(4-aminopiperidin-1-yl)-3-(4-bromophenyl)-1-oxopropan-2-yl]-1-(2,4-dichlorophenyl)cyclopropane-1-carboxamide	699203: Inhibition of GCS assessed as amount of UDP glucose after 3 hrs by Fluorometry analysis	ic50	0.0030	uM
N-[(2S)-1-[(1R,5S)-3-amino-8-azabicyclo[3.2.1]octan-8-yl]-3-(4-bromophenyl)-1-oxopropan-2-yl]-1-(2,4-dichlorophenyl)cyclopropane-1-carboxamide	699203: Inhibition of GCS assessed as amount of UDP glucose after 3 hrs by Fluorometry analysis	ic50	0.0030	uM
N-[(2S)-1-[(1S,5R)-3-amino-8-azabicyclo[3.2.1]octan-8-yl]-3-(2,4-dichlorophenyl)-1-oxopropan-2-yl]-1-[4-(trifluoromethoxy)phenyl]cyclopropane-1-carboxamide	699203: Inhibition of GCS assessed as amount of UDP glucose after 3 hrs by Fluorometry analysis	ic50	0.0030	uM
2-[4-(2-hydroxypropan-2-yl)phenyl]-6-(3-methyloxetan-3-yl)-4-[2-(2,2,2-trifluoroethoxy)phenyl]-3H-pyrrolo[3,4-c]pyridin-1-one	1896613: Inhibition of human GCS using C8-ceramide and UDP-glucose as substrate incubated for 1 hrs by Rapidfire mass spectrometric analysis	ic50	0.0036	uM
N-[(2R)-1-[[(3S)-1-azabicyclo[2.2.2]octan-3-yl]amino]-1-oxo-3-phenylmethoxypropan-2-yl]-2-[2-chloro-4-(trifluoromethyl)phenoxy]pyridine-3-carboxamide	626356: Inhibition of GCS activity in human A549 cells assessed as amount of GM1 on the cell membrane after 72 hrs by FL-CTB-based fluorescent microscopy	ic50	0.0040	uM
1-(2,4-dichlorophenyl)-N-[(2S)-3-(2,4-dichlorophenyl)-1-(4-methylpiperazin-1-yl)-1-oxopropan-2-yl]cyclopropane-1-carboxamide	699202: Inhibition of GCS in human A549 cells assessed as decrease in GM1 synthesis after 72 hrs by Fluorescence assay	ic50	0.0040	uM
N-[(2S)-3-(4-bromophenyl)-1-[2-(dimethylamino)ethyl-methylamino]-1-oxopropan-2-yl]-1-(2,4-dichlorophenyl)cyclopropane-1-carboxamide	699203: Inhibition of GCS assessed as amount of UDP glucose after 3 hrs by Fluorometry analysis	ic50	0.0040	uM
4-[2-(2,2-difluoroethoxy)phenyl]-2-[4-(2-hydroxypropan-2-yl)phenyl]-6-(3-methyloxetan-3-yl)-3H-pyrrolo[3,4-c]pyridin-1-one	1896613: Inhibition of human GCS using C8-ceramide and UDP-glucose as substrate incubated for 1 hrs by Rapidfire mass spectrometric analysis	ic50	0.0043	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects expression, decreases expression, affects cotreatment, increases expression	7
Doxorubicin	decreases expression, increases expression, decreases reaction, decreases response to substance, decreases abundance	4
Estradiol	affects cotreatment, decreases expression, increases expression	4
Particulate Matter	increases abundance, increases expression, decreases expression	4
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	3
Valproic Acid	increases expression, decreases expression	3
bisphenol A	affects expression, increases expression	2
trichostatin A	increases expression, affects expression	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	2
bisphenol S	decreases expression, affects cotreatment, increases expression	2
Resveratrol	decreases expression	2
Vorinostat	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Cocaine	increases expression	2
Indomethacin	decreases expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Asbestos, Crocidolite	affects expression, increases expression	2
Lithium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
geldanamycin	increases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
hydroquinone	increases expression	1

ChEMBL screening assays

44 unique, capped per target: 41 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1099879	Binding	Inhibition of GCS by cell-based assay	Dual-action lipophilic iminosugar improves glycemic control in obese rodents by reduction of visceral glycosphingolipids and buffering of carbohydrate assimilation. — J Med Chem
CHEMBL5304914	Functional	Human GCS enzymatic assay	Data for DCP probe TP-060

Cellosaurus cell lines

7 cell lines: 7 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2KD	Abcam HeLa UGCG KO	Cancer cell line	Female
CVCL_B3T2	HeLa-mCAT#8 TAL-UG#3	Cancer cell line	Female
CVCL_B3T3	HeLa-mCAT#8 TAL-UG#7	Cancer cell line	Female
CVCL_B3T4	HeLa-mCAT#8 TAL-CE#14-UG#2	Cancer cell line	Female
CVCL_TW23	HAP1 UGCG (-) 1	Cancer cell line	Male
CVCL_TW24	HAP1 UGCG (-) 2	Cancer cell line	Male
CVCL_TW25	HAP1 UGCG (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04996485	PHASE4	UNKNOWN	Scientific Substantiation and Assessment of the Effectiveness of Pathogenetic Methods of Therapy for Congenital Ichthyosis in Children
NCT00004690	PHASE3	COMPLETED	Phase III Study of Monolaurin Cream Therapy for Patients With Congenital Ichthyosis
NCT05295732	PHASE3	COMPLETED	The ASCEND Study: Evaluating TMB-001 in the Treatment of RXLI or ARCI Ichthyosis
NCT02864082	PHASE2	COMPLETED	A Safety and Tolerability Study of Topical PAT-001 in Congenital Ichthyosis
NCT03041038	PHASE2	COMPLETED	The Efficacy and Safety of Secukinumab in Patients With Ichthyoses
NCT04154293	PHASE2	COMPLETED	A Vehicle Controlled Study to Evaluate Safety and Efficacy of Topical TMB-001 for Treatment of Congenital Ichthyosis
NCT04697056	PHASE2	TERMINATED	A Study to Evaluate the Efficacy and Safety of Imsidolimab (ANB019) in the Treatment of Participants With Ichthyosis
NCT06136403	PHASE2	RECRUITING	A 44-week Monocentric Open Study Assessing the Efficacy and Safety of Deucravacitinib in Adults With Inflammatory Genodermatoses
NCT06362447	PHASE2	NOT_YET_RECRUITING	Efficacy of Injectable Gentamicin in Hereditary Ichthyosis
NCT04549792	EARLY_PHASE1	COMPLETED	An Open-Label and Long-Term Extension Study to Evaluate the Efficacy and Safety of Ustekinumab in the Treatment of Patients With Ichthyoses
NCT07050810	EARLY_PHASE1	ENROLLING_BY_INVITATION	Thera-Clean® Microbubbles System in Patients With Skin Diseases
NCT00074685	Not specified	COMPLETED	National Registry for Ichthyosis and Related Disorders
NCT02655861	Not specified	TERMINATED	A Multi-center, Prospective Evaluation of Infants and Children With Congenital Ichthyosis
NCT03051347	Not specified	COMPLETED	Asthma and Atopic Dermatitis Validation of PROMIS Pediatric Instruments
NCT03417856	Not specified	ENROLLING_BY_INVITATION	Defining the Skin and Blood Biomarkers of Ichthyosis
NCT03464994	Not specified	COMPLETED	Ophthalmological Abnormalities in Hereditary Ichthyosis (ICHTYO-KERATO)
NCT03641261	Not specified	COMPLETED	Therapeutic Education Using an Internet Application in Hereditary Ichthyosis
NCT03796052	Not specified	COMPLETED	Study Determining Safety and Efficacy of Avena Sativa (Oat) Skincare Products for Treating Skin Dryness and Itching in Cancer Patients
NCT05610306	Not specified	COMPLETED	Quality of Life in Middle-aged and Older Patients With Congenital Ichthyosis
NCT05954416	Not specified	RECRUITING	FARD (RaDiCo Cohort) (RaDiCo-FARD)
NCT06123091	Not specified	UNKNOWN	Exploring Patient Reported Outcomes in Inherited Ichthyosis
NCT06330324	Not specified	ENROLLING_BY_INVITATION	Reproductive Options in Inherited Skin Diseases
NCT06330350	Not specified	RECRUITING	Qualitative Study in Patients With Genodermatoses and Healthcare Professionals on Reproductive Counselling
NCT07066150	Not specified	COMPLETED	A Clinical Evaluation of Marula-Derived Ceramide Cream on Skin Barrier Function Enhancement