ASAH1

Summary

ASAH1 (N-acylsphingosine amidohydrolase 1, HGNC:735) is a protein-coding gene on chromosome 8p22, encoding Acid ceramidase (Q13510). Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH.

This gene encodes a member of the acid ceramidase family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. Processing of this preproprotein generates alpha and beta subunits that heterodimerize to form the mature lysosomal enzyme, which catalyzes the degradation of ceramide into sphingosine and free fatty acid. This enzyme is overexpressed in multiple human cancers and may play a role in cancer progression. Mutations in this gene are associated with the lysosomal storage disorder, Farber lipogranulomatosis, and a neuromuscular disorder, spinal muscular atrophy with progressive myoclonic epilepsy.

Source: NCBI Gene 427 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ASAH1-related sphingolipidosis (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 1,058 total — 70 pathogenic, 51 likely-pathogenic
• Phenotypes (HPO): 123
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_177924

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:735
Approved symbol	ASAH1
Name	N-acylsphingosine amidohydrolase 1
Location	8p22
Locus type	gene with protein product
Status	Approved
Aliases	AC, PHP32, FLJ21558, ACDase
Ensembl gene	ENSG00000104763
Ensembl biotype	protein_coding
OMIM	613468
Entrez	427

Gene structure

Transcript identifiers

Ensembl transcripts: 69 — 29 protein_coding, 22 nonsense_mediated_decay, 17 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000314146, ENST00000381733, ENST00000517409, ENST00000518087, ENST00000518746, ENST00000519468, ENST00000519545, ENST00000520051, ENST00000520781, ENST00000521542, ENST00000523593, ENST00000523744, ENST00000635756, ENST00000635769, ENST00000635944, ENST00000635998, ENST00000636009, ENST00000636033, ENST00000636050, ENST00000636128, ENST00000636160, ENST00000636171, ENST00000636269, ENST00000636299, ENST00000636435, ENST00000636455, ENST00000636494, ENST00000636537, ENST00000636563, ENST00000636577, ENST00000636691, ENST00000636701, ENST00000636715, ENST00000636719, ENST00000636815, ENST00000636823, ENST00000636828, ENST00000636920, ENST00000636997, ENST00000637013, ENST00000637014, ENST00000637095, ENST00000637202, ENST00000637244, ENST00000637343, ENST00000637429, ENST00000637484, ENST00000637528, ENST00000637536, ENST00000637561, ENST00000637603, ENST00000637609, ENST00000637636, ENST00000637638, ENST00000637718, ENST00000637752, ENST00000637790, ENST00000637792, ENST00000637805, ENST00000637840, ENST00000637857, ENST00000637872, ENST00000637898, ENST00000637922, ENST00000637946, ENST00000637991, ENST00000638028, ENST00000638069, ENST00000961129

RefSeq mRNA: 4 — MANE Select: NM_177924 NM_001127505, NM_001363743, NM_004315, NM_177924

CCDS: CCDS47813, CCDS6005, CCDS6006, CCDS87583

Canonical transcript exons

ENST00000637790 — 14 exons

Exon	Start	End
ENSE00001296427	18058835	18058891
ENSE00001316023	18059341	18059464
ENSE00003474471	18062279	18062423
ENSE00003485505	18061686	18061740
ENSE00003488563	18075541	18075587
ENSE00003490227	18069792	18069878
ENSE00003497678	18071300	18071390
ENSE00003540193	18067220	18067298
ENSE00003564831	18063185	18063230
ENSE00003575713	18061377	18061458
ENSE00003662942	18064457	18064531
ENSE00003681050	18059572	18059703
ENSE00003799516	18055992	18057623
ENSE00003843873	18083981	18084107

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 99.80.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 135.4995 / max 2742.7372, expressed in 1822 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92062	128.5114	1822
92064	3.0687	1430
92060	1.8389	163
92063	1.6235	807
92061	0.2886	86
92059	0.1683	56

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
heart right ventricle	UBERON:0002080	99.80	gold quality
visceral pleura	UBERON:0002401	99.78	gold quality
pancreatic ductal cell	CL:0002079	99.67	gold quality
pigmented layer of retina	UBERON:0001782	99.64	gold quality
retina	UBERON:0000966	99.61	gold quality
pleura	UBERON:0000977	99.56	gold quality
myocardium	UBERON:0002349	99.48	gold quality
parietal pleura	UBERON:0002400	99.47	gold quality
nasal cavity epithelium	UBERON:0005384	99.46	gold quality
monocyte	CL:0000576	99.40	gold quality
renal medulla	UBERON:0000362	99.37	gold quality
mononuclear cell	CL:0000842	99.36	gold quality
cardiac ventricle	UBERON:0002082	99.35	gold quality
cardiac atrium	UBERON:0002081	99.33	gold quality
heart left ventricle	UBERON:0002084	99.33	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.33	gold quality
lower lobe of lung	UBERON:0008949	99.33	gold quality
leukocyte	CL:0000738	99.32	gold quality
right atrium auricular region	UBERON:0006631	99.32	gold quality
nephron tubule	UBERON:0001231	99.31	gold quality
left ventricle myocardium	UBERON:0006566	99.29	gold quality
thyroid gland	UBERON:0002046	99.28	gold quality
bronchial epithelial cell	CL:0002328	99.27	gold quality
left lobe of thyroid gland	UBERON:0001120	99.27	gold quality
germinal epithelium of ovary	UBERON:0001304	99.27	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	99.27	gold quality
skin of hip	UBERON:0001554	99.25	gold quality
caput epididymis	UBERON:0004358	99.25	gold quality
heart	UBERON:0000948	99.22	gold quality
kidney epithelium	UBERON:0004819	99.21	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 25.

Experiment	Marker?	Max mean expression
E-MTAB-7381	yes	1725.18
E-HCAD-4	yes	203.35
E-CURD-122	yes	68.35
E-MTAB-6701	yes	50.00
E-MTAB-8410	yes	45.30
E-HCAD-10	yes	39.64
E-CURD-46	yes	36.23
E-GEOD-137537	yes	29.51
E-CURD-88	yes	29.50
E-MTAB-9467	yes	27.74
E-MTAB-9221	yes	27.19
E-MTAB-7316	yes	25.84
E-MTAB-10553	yes	25.59
E-MTAB-6678	yes	23.97
E-MTAB-10287	yes	23.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, FLCN, KLF6, TFE3, TP53

miRNA regulators (miRDB)

81 targeting ASAH1, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4282	99.99	75.36	6408
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4789-5P	99.98	70.76	2721
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-568	99.98	69.86	2084
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698

Literature-anchored findings (GeneRIF, showing 40)

• acid ceramidase has a central role in sphingolipid metabolism (PMID:12764132)
• biochemistry of acid ceramidase reaction with acid sphingomyelinase (PMID:12815059)
• p53-dependent expression of acid ceramidase and blockage of A-SMase activation play pivotal roles in protection from gamma-radiation of cells with endogenous functional p53. (PMID:15088070)
• These results provide the first characterization of the Acid Ceremidase promoter from any species and demonstrate that Kruppel-like factor 6 (KLF6) is one transcription factor involved in the regulation of AC gene expression. (PMID:16500425)
• upregulation of haCER1 and AC mediates the Ca2+(o)-induced growth arrest and differentiation of keratinocytes by generating sphingosine and its phosphate (PMID:17713573)
• AC is a critical regulator of prostate cancer progression by affecting not only tumor cell proliferation and migration but also responses to drug therapy (PMID:17881906)
• Positive selection is possibly operating on ASAH1 in the modern human population. (PMID:18245333)
• acid ceramidase was constitutively overexpressed in leukemic LGLs and its inhibition induced apoptosis of leukemic LGLs (PMID:18477771)
• These data identify the ACTH/cAMP signaling pathway and CREB as transcriptional regulators of the ASAH1 gene in the human adrenal cortex. (PMID:19298866)
• high ASAH1 expression correlates with grading & estrogen receptor (ER) status in breast cancer; high ASAH1 expression was associated with larger tumor size; a better prognosis of patients with higher ASAH1 expression in ER-positive subgroup was detected (PMID:19905902)
• Both acidic ceramidase (aCDase) and neutral ceramidase (nCDase) activities declined after low- and high-UVB, but returned to normal only in low-UVB cells (PMID:20520628)
• Acid ceramidase (aCDase) is responsible for ceramide degradation within mammalian cells. An inherited deficiency of aCDase activity results in Farber disease. (PMID:20871013)
• cells deficient in acid ceramidase (aCDase) also exhibited defects in CCL5 induction, whereas cells deficient in sphingosine kinase-1 and -2 exhibited higher levels of CCL5. (PMID:21335555)
• This study supports that the ASAH1 gene may be a potential candidate gene for schizophrenia in Han Chinese subjects. (PMID:21375364)
• a mechanism through which genistein promotes sphingolipid metabolism and support a role for ASAH1 in breast cancer cell growth. (PMID:21493710)
• the level of AC did not correlate with the sensitivity of HNSCC cells to Fas-induced apoptosis. (PMID:21504271)
• down-regulation of aCDase alone or in combination with DTIC may represent a useful tool in the treatment of metastatic melanoma. (PMID:21700700)
• Identification of cystatin SA as a novel inhibitor of acid ceramidase. (PMID:21846728)
• A report of two siblings with Farber disease who carry a novel V97G ASAH1 mutation with the parents and a sister being asymptomatic carriers. (PMID:21893389)
• ASAH1 as a pivotal regulator of steroidogenic capacity in the human adrenal cortex. (PMID:22261821)
• Acid ceramidase, through sphingosine 1-phosphate, promotes an invasive phenotype in prostate cancer by causing overexpression and secretion of cathepsin B through activation and nuclear expression of Ets1. (PMID:22322590)
• ASAH1 inhibition synergistically sensitizes lung cancer cells resistant to the antiproliferative effect of choline kinase alpha inhibitors. (PMID:22515519)
• Our results reveal a wide phenotypic spectrum associated with ASAH1 mutations in spinal muscular atrophy associated with progressive myoclonal epilepsy. (PMID:22703880)
• results demonstrate that ASAH1 is a novel coregulatory protein that represses SF-1 function by directly binding to the receptor on SF-1 target gene promoters and identify a key role for nuclear lipid metabolism in regulating gene transcription (PMID:22927646)
• These observations confirm ASAH1 as a therapeutic target in advanced and chemoresistant forms of prostate cancer (PMID:23423838)
• Acid ceramidase is a prognostic factor in epithelial ovarian cancer (PMID:23518908)
• This work unravels for the first time the mutations underlying the neonatal form of Farber disease and represents the first report of a large deletion identified in the ASAH1 gene. (PMID:23707712)
• Depletion of both Akt2 and ASAH1 is much more potent than depleting each alone at inhibiting neoplastic cell viability/proliferation and invasion. (PMID:23777806)
• Immunohistochemical analysis of human prostate cancer tissues revealed higher levels of ASAH1 after radiotherapy failure. (PMID:24091326)
• Acid ceramidase promotes nuclear export of PTEN through sphingosine 1-phosphate mediated Akt signaling. (PMID:24098536)
• novel ASAH1 mutations affecting polypyrimidine tract deletion, and exon skipping and resulting in Farber lipogranulomatosis (PMID:24355074)
• high ASAH1 expression is generally associated with an improved prognosis in invasive breast cancer independent of adjuvant treatment and could also be valuable as prognostic factor for pre-invasive DCIS. (PMID:25131496)
• Data suggest up-regulation of ASAH1 activity by androgen in androgen-sensitive prostate cancer cells (not other cancer cells) is due to prolonged stability of ASAH1 by androgen-stimulated induction of USP2 (ubiquitin specific peptidase 2) expression. (PMID:25888580)
• AC-controlled sphingolipid metabolism may play an important role in the control of melanoma proliferation (PMID:26553872)
• Genetic or pharmacological acid ceramidase inhibition promotes cisplatin cytotoxicity in head and neck tumor cells. (PMID:26687835)
• Our findings indicate that hypomorphic mutations in ASAH1 may result in an osteoarticular phenotype with a juvenile phase resembling rheumatoid arthritis that evolves to osteolysis as the final stage in the absence of neurologic signs. This observation delineates a novel type of recessively inherited peripheral osteolysis and illustrates the long-term skeletal manifestations of acid ceramidase deficiency (Farber’s disease (PMID:26945816)
• This study describes for the first time the association between ASAH1 variants and an adult SMA phenotype with no myoclonic epilepsy nor death in early age, thus expanding the phenotypic spectrum of ASAH1-related SMA. (PMID:27026573)
• We report an atypical presentation of Farber disease with her pathology and associated genetic defect. This case expands the phenotypic spectrum of Farber disease to include novel mutations of ASAH1, which pose a diagnostic challenge. (PMID:27411168)
• The present report describes a 9-year-old girl with novel clinical phenotype of a patient with polyarticular arthritis followed by symptoms of SMA due to acid ceramidase deficiency. Whole exome sequencing identified compound heterozygous pathogenic mutation in the N-acylsphingosine amidohydrolase 1 gene. (PMID:27650050)
• Acid ceramidase plays a critical role in acute myeloid leukemia cell survival via regulation of both sphingolipid levels and Mcl-1. (PMID:27825124)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	asah1b	ENSDARG00000034817
danio_rerio	asah1a	ENSDARG00000037091
mus_musculus	Asah1	ENSMUSG00000031591
rattus_norvegicus	Asah1	ENSRNOG00000010034
caenorhabditis_elegans		WBGENE00009192
caenorhabditis_elegans	asah-1	WBGENE00010769

Paralogs (1): NAAA (ENSG00000138744)

Protein

Protein identifiers

Acid ceramidase — Q13510 (reviewed: Q13510)

Alternative names: Acylsphingosine deacylase, Glycosylceramide deacylase, N-acylethanolamine hydrolase ASAH1, N-acylsphingosine amidohydrolase, Putative 32 kDa heart protein

All UniProt accessions (38): A0A1B0GTA6, A0A1B0GTD4, A0A1B0GTM3, A0A1B0GTP7, A0A1B0GTQ7, A0A1B0GTX9, A0A1B0GTZ5, A0A1B0GU06, Q13510, A0A1B0GU62, A0A1B0GU70, A0A1B0GUA4, A0A1B0GUB3, A0A1B0GUE3, A0A1B0GUG1, A0A1B0GUH5, A0A1B0GUJ2, A0A1B0GUJ3, A0A1B0GUP1, A0A1B0GUQ5, A0A1B0GUW4, A0A1B0GV06, A0A1B0GV88, A0A1B0GV95, A0A1B0GVA3, A0A1B0GVA8, A0A1B0GVC9, A0A1B0GVE7, A0A1B0GVG2, A0A1B0GVJ1, A0A1B0GVL2, A0A1B0GVY5, A0A1B0GW30, A0A1B0GW48, A0A1B0GW66, A0A1B0GW68, A0A1B0GWC9, E7EMM4

UniProt curated annotations — full annotation on UniProt →

Function. Lysosomal ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at acidic pH. Ceramides, sphingosine, and its phosphorylated form sphingosine-1-phosphate are bioactive lipids that mediate cellular signaling pathways regulating several biological processes including cell proliferation, apoptosis and differentiation. Has a higher catalytic efficiency towards C12-ceramides versus other ceramides. Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine. For the reverse synthetic reaction, the natural sphingosine D-erythro isomer is more efficiently utilized as a substrate compared to D-erythro-dihydrosphingosine and D-erythro-phytosphingosine, while the fatty acids with chain lengths of 12 or 14 carbons are the most efficiently used. Also has an N-acylethanolamine hydrolase activity. By regulating the levels of ceramides, sphingosine and sphingosine-1-phosphate in the epidermis, mediates the calcium-induced differentiation of epidermal keratinocytes. Also indirectly regulates tumor necrosis factor/TNF-induced apoptosis. By regulating the intracellular balance between ceramides and sphingosine, in adrenocortical cells, probably also acts as a regulator of steroidogenesis. May directly regulate steroidogenesis by binding the nuclear receptor NR5A1 and negatively regulating its transcriptional activity.

Subunit / interactions. Heterodimer; disulfide-linked. The heterodimer is composed of the disulfide-linked alpha and beta chains produced by autocatalytic cleavage of the precursor. Isoform 2: May interact with NR5A1 in the nucleus; the direct interaction would negatively regulate NR5A1 transcriptional activity.

Subcellular location. Lysosome. Secreted Nucleus. Cytoplasm.

Tissue specificity. Broadly expressed with higher expression in heart.

Post-translational modifications. N-glycosylated. Proteolytically cleaved into two chains alpha and beta that remain associated via a disulfide bond. Cleavage gives rise to a conformation change that activates the enzyme. The same catalytic Cys residue mediates the autoproteolytic cleavage and subsequent hydrolysis of lipid substrates. The beta chain may undergo an additional C-terminal processing.

Disease relevance. Farber lipogranulomatosis (FRBRL) [MIM:228000] An autosomal recessive lysosomal storage disorder characterized by subcutaneous lipid-loaded nodules, excruciating pain in the joints and extremities, and marked accumulation of ceramide in lysosomes. Disease severity is variable. The most severe disease subtype is a rare neonatal form with death occurring before 1 year of age. The disease is caused by variants affecting the gene represented in this entry. Spinal muscular atrophy with progressive myoclonic epilepsy (SMAPME) [MIM:159950] An autosomal recessive neuromuscular disorder characterized by childhood onset of motor deficits and progressive myoclonic seizures, after normal developmental milestones. Proximal muscle weakness and generalized muscular atrophy are due to degeneration of spinal motor neurons. Myoclonic epilepsy is generally resistant to conventional therapy. The disease course is progressive and leads to respiratory muscle involvement and severe handicap or early death from respiratory insufficiency. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by Ca(2+), Mg(2+) and Na(+) cations. Inhibited by Zn(2+). Phosphatidylserine and phosphatidic acid stimulate while cardiolipin, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and sphingomyelin inhibit the reverse ceramide synthase activity. Phosphatidic acid, phosphatidylinositol and C16-ceramide inhibit the ceramidase/hydrolase activity.

Induction. Up-regulated by Ca(2+).

Pathway. Lipid metabolism; sphingolipid metabolism.

Miscellaneous. Switches substrate specificity upon intralysosomal accumulation of glycosphingolips. Such is the case in Gaucher disease where the regular catabolism of glucosylceramide (GluCer) fails due to the lack of GBA1 activity, its accumulation triggers the alternative catabolism by acid ceramidase which deacylates GluCer producing a free fatty acid and glucosylsphingosine (glucosylsphing-4-enine, GluSph). Similarly, the intralysosomal accumulation of globoside Gb3 in Fabry disease due to an inactive GLA triggers its alternative catabolism by acid ceramidase, generating lysoGb3. Formation of lyso-glycosphingolipids might have harmful side-effects and contribute to the pathology, for instance GluSph causes an aberrant activation of mTORC1, suppressing normal lysosomal functions, including the clearance of pathogenic alpha-synuclein species. Mutagenesis in position: 25:L->A (Loss of interaction with NR5A1).

Similarity. Belongs to the acid ceramidase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13510-1	1	yes
Q13510-2	2
Q13510-3	3

RefSeq proteins (4): NP_001120977, NP_001350672, NP_004306, NP_808592* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016699	Acid_ceramidase-like	Family
IPR029130	Acid_ceramidase_N	Domain
IPR029132	CBAH/NAAA_C	Domain

Pfam: PF02275, PF15508

Enzyme classification (BRENDA):

• EC 3.5.1.23 — ceramidase (BRENDA: 26 organisms, 303 substrates, 355 inhibitors, 64 Km, 14 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
N-LAUROYLSPHINGOSINE	0.149–0.4132	5
D-ERYTHRO-C12-4-NITROBENZO-2-OXA-1,3-DIAZOLE-CER	0.0393–0.0601	3
N-[12-[(7-NITRO-2-1,3-BENZOXADIAZOL-4-YL)AMINE]D	0.0155–0.066	3
(2R,3Z)-2-([(2E)-1-HYDROXY-12-[(7-NITRO-2,1,3-BE	0.087–0.19	2
N-[(2S,3R,4E)-1,3-DIHYDROXY-14-[(7-NITRO-2,1,3-B	0.193–0.204	2
N-[(2S,3R,4E)-1,3-DIHYDROXYNONADEC-4-EN-2-YL]-12	0.085–0.11	2
N-[(2S,3R,4E)-13-[[9-(ETHYLAMINO)-5-OXO-5H-BENZO	0.036–0.082	2
N-[(2S,3R,4E)-7-[[9-(DIETHYLAMINO)-5-OXO-5H-BENZ	0.1418–0.1818	2
(13E)-N-[(2S,3R,4E)-1,3-DIHYDROXY-7-[(2-OXO-2H-1	0.033	1
(15E)-N-[(2S,3R,4E)-1,3-DIHYDROXY-7-[(2-OXO-2H-1	0.04	1
(2R)-N-[(2S,3R,4E)-1,3-DIHYDROXY-7-[(2-OXO-2H-1-	0.042	1
(2S)-N-[(2S,3R,4E)-1,3-DIHYDROXY-7-[(2-OXO-2H-1-	0.021	1
(4E,2S,3R)-2-N-(10-PYRENEDECANOYL)-1,3,17-TRIHYD	0.0005	1
(9E)-N-[(2S,3R,4E)-1,3-DIHYDROXY-7-[(2-OXO-2H-1-	0.139	1
2,4-DIDEOXY-2-(HEXADECANOYLAMINO)-5-O-(2-OXO-2H-	0.016	1

Catalyzed reactions (Rhea), 12 shown:

• an N-acylsphing-4-enine + H2O = sphing-4-enine + a fatty acid (RHEA:20856)
• a beta-D-glucosyl-(1<->1’)-N-acylsphing-4-enine + H2O = beta-D-glucosyl-(1<->1)-sphing-4-enine + a fatty acid (RHEA:30915)
• N-hexadecanoylsphing-4-enine + H2O = sphing-4-enine + hexadecanoate (RHEA:38891)
• N-octadecanoylsphing-4-enine + H2O = sphing-4-enine + octadecanoate (RHEA:41279)
• N-tetradecanoylsphing-4-enine + H2O = sphing-4-enine + tetradecanoate (RHEA:41287)
• N-dodecanoylsphing-4-enine + H2O = dodecanoate + sphing-4-enine (RHEA:41291)
• N-(hexanoyl)sphing-4-enine + H2O = hexanoate + sphing-4-enine (RHEA:41295)
• N-(9Z-octadecenoyl)-sphing-4-enine + H2O = sphing-4-enine + (9Z)-octadecenoate (RHEA:41299)
• N-dodecanoyl-(4R)-hydroxysphinganine + H2O = (4R)-hydroxysphinganine + dodecanoate (RHEA:41303)
• N-octanoylsphing-4-enine + H2O = octanoate + sphing-4-enine (RHEA:45092)
• N-(dodecanoyl)-sphinganine + H2O = dodecanoate + sphinganine (RHEA:45448)
• N-dodecanoylethanolamine + H2O = dodecanoate + ethanolamine (RHEA:45456)

UniProt features (106 total): sequence variant 29, strand 17, mutagenesis site 17, helix 13, turn 7, glycosylation site 6, sequence conflict 5, splice variant 3, site 3, chain 2, disulfide bond 2, signal peptide 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5U7Z	X-RAY DIFFRACTION	2.5
6MHM	X-RAY DIFFRACTION	2.74

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13510-F1	91.97	0.77

Functional residue map

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

Catalytic / active sites (4): 143 (nucleophile); 162 (important for catalytic activity); 320 (important for catalytic activity); 333 (important for catalytic activity)

Disulfide bonds (2): 31–340, 388–392

Glycosylation sites (6): 286, 342, 348, 173, 195, 259

Mutagenesis-validated functional residues (17):

Position	Phenotype
80	no effect on autocatalytic processing, but loss of ceramidase activity, when associated with 165-q–q-167.
141	decreased rate of autocatalytic processing.
143	loss of autocatalytic processing. loss of ceramidase activity.
159	strongly decreased autocatalytic processing. moderately decreased ceramidase activity.
162	strongly decreased autocatalytic processing. strongly decreased ceramidase activity.
165–167	no effect on autocatalytic processing, but loss of ceramidase activity, when associated with q-80.
169–171	moderately decreased autocatalytic processing, but loss of ceramidase activity, when associated with q-176.
173	loss of ceramide catabolic process.
176	moderately decreased autocatalytic processing, but loss of ceramidase activity, when associated with 169-q–q-171.
195	no effect on ceramide catabolic process.
259	loss of ceramide catabolic process.
286	no effect on ceramide catabolic process.
320	strongly decreased autocatalytic processing. mildly decreased ceramidase activity.
328–330	no effect on autocatalytic processing, but strongly decreased ceramidase activity.
333	mildly decreased autocatalytic processing. loss of ceramidase activity.
342	loss of ceramide catabolic process.
348	no effect on ceramide catabolic process.

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-9857377	Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-9730414	MITF-M-regulated melanocyte development
R-HSA-9856651	MITF-M-dependent gene expression

MSigDB gene sets: 616 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_CERAMIDE_CATABOLIC_PROCESS, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, BIOCARTA_EDG1_PATHWAY, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, MODULE_45, GOBP_POLYOL_METABOLIC_PROCESS, KEGG_LYSOSOME, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, BOHN_PRIMARY_IMMUNODEFICIENCY_SYNDROM_DN, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS

GO Biological Process (11): fatty acid metabolic process (GO:0006631), keratinocyte differentiation (GO:0030216), sphingosine biosynthetic process (GO:0046512), ceramide biosynthetic process (GO:0046513), ceramide catabolic process (GO:0046514), regulation of steroid biosynthetic process (GO:0050810), regulation of programmed necrotic cell death (GO:0062098), cellular response to tumor necrosis factor (GO:0071356), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (8): transcription corepressor activity (GO:0003714), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides (GO:0016811), nuclear receptor binding (GO:0016922), N-acylsphingosine amidohydrolase activity (GO:0017040), fatty acid amide hydrolase activity (GO:0017064), protein binding (GO:0005515), hydrolase activity (GO:0016787), hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds (GO:0016810)

GO Cellular Component (10): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), lysosome (GO:0005764), membrane (GO:0016020), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), tertiary granule lumen (GO:1904724), ficolin-1-rich granule lumen (GO:1904813), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Innate Immune System	1
Glycosphingolipid metabolism	1
MITF-M-dependent gene expression	1
Sphingolipid metabolism	1
Immune System	1
Metabolism of lipids	1
Metabolism	1
Developmental Biology	1
MITF-M-regulated melanocyte development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
lipid metabolic process	2
ceramide metabolic process	2
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	2
intracellular organelle lumen	2
monocarboxylic acid metabolic process	1
epidermal cell differentiation	1
skin development	1
sphingosine metabolic process	1
diol biosynthetic process	1
sphingoid biosynthetic process	1
sphingolipid biosynthetic process	1
sphingolipid catabolic process	1
steroid biosynthetic process	1
regulation of steroid metabolic process	1
regulation of lipid biosynthetic process	1
regulation of programmed cell death	1
programmed necrotic cell death	1
response to tumor necrosis factor	1
cellular response to cytokine stimulus	1
primary metabolic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
binding	1
catalytic activity	1
hydrolase activity	1
intracellular membrane-bounded organelle	1
lytic vacuole	1
lysosome	1
vacuolar lumen	1
extracellular vesicle	1
tertiary granule	1
ficolin-1-rich granule	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2480 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASAH1	ASAH2	Q9NR71	937
ASAH1	SMPD1	P17405	909
ASAH1	PSAP	P07292	907
ASAH1	ASAH2B	P0C7U1	894
ASAH1	GALC	P54803	835
ASAH1	ACER1	Q8TDN7	827
ASAH1	GLA	P06280	815
ASAH1	SPTLC1	O15269	809
ASAH1	ACER2	Q5QJU3	789
ASAH1	GBA1	P04062	788
ASAH1	ARSA	P15289	782
ASAH1	CERK	Q8TCT0	776
ASAH1	SPHK1	Q9NYA1	766
ASAH1	SPTLC2	O15270	757
ASAH1	SPTLC3	Q9NUV7	755

IntAct

57 interactions, top by confidence:

A	B	Type	Score
AKR7A3	AKR7A2	psi-mi:“MI:0914”(association)	0.890
ASH2L	KMT2D	psi-mi:“MI:0914”(association)	0.890
AAGAB	AP2A2	psi-mi:“MI:0914”(association)	0.670
ASAH1	NR5A1	psi-mi:“MI:0914”(association)	0.550
NR5A1	ASAH1	psi-mi:“MI:0914”(association)	0.550
NR5A1	ASAH1	psi-mi:“MI:0915”(physical association)	0.550
AAGAB	STXBP3	psi-mi:“MI:0914”(association)	0.530
CYP1A2	PGRMC1	psi-mi:“MI:0914”(association)	0.530
AKR7A3	ASAH1	psi-mi:“MI:0914”(association)	0.530
CD53	FAM171A2	psi-mi:“MI:0914”(association)	0.530
CYP17A1	ASAH1	psi-mi:“MI:0914”(association)	0.460
SRPK1	ASAH1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
Bub1b	NDC80	psi-mi:“MI:0915”(physical association)	0.400
HSPB2	ASAH1	psi-mi:“MI:0915”(physical association)	0.370
CAMK1D	ASAH1	psi-mi:“MI:0915”(physical association)	0.370
NR5A1	PSAP	psi-mi:“MI:0914”(association)	0.350
HDAC1	ASAH1	psi-mi:“MI:0914”(association)	0.350
	ASAH1	psi-mi:“MI:0914”(association)	0.350
MC2R	ASAH1	psi-mi:“MI:0914”(association)	0.350
NR0B1	ASAH1	psi-mi:“MI:0914”(association)	0.350
	VPS37C	psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
OSTM1	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (96): ASAH1 (Affinity Capture-MS), ASAH1 (Affinity Capture-MS), ASAH1 (Affinity Capture-MS), ASAH1 (Affinity Capture-MS), NEFH (Affinity Capture-MS), CAMK2B (Affinity Capture-MS), ASAH1 (Affinity Capture-MS), ASAH1 (Two-hybrid), ASAH1 (Affinity Capture-MS), ASAH1 (Affinity Capture-MS), ASAH1 (Affinity Capture-MS), ASAH1 (Affinity Capture-MS), ASAH1 (Affinity Capture-MS), ASAH1 (Affinity Capture-MS), ASAH1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0P6JG37, A0A383ZFX3, A5A6P2, A6MFL0, A8QL51, A8QL52, B0VXW0, B5AR80, B5U6Y8, F8J2D3, F8S101, G8XQX1, J7H670, O45686, O62146, P0C2D5, P12256, P23780, P81382, P81383, Q06K61, Q09551, Q13510, Q17QB3, Q19426, Q2VQV9, Q4JHE2, Q54CS6, Q54EW2, Q554H5, Q55BZ5, Q5KTC7, Q5MIX2, Q5U2V4, Q5UR76, Q60HH4, Q6L6S1, Q6P7S1, Q6STF1, Q6TGQ8

Diamond homologs: A0A0P6JG37, A0A383ZFX3, A5A6P2, G1T7U7, H0VCJ6, O45686, Q02083, Q09551, Q13510, Q17QB3, Q5KTC7, Q60HH4, Q6P7S1, Q9D7V9, Q9GUI1, Q9WV54

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1058 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	70
Likely pathogenic	51
Uncertain significance	367
Likely benign	392
Benign	109

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070162	NC_000008.10:g.(?17927301)(17930785_?)del	Pathogenic
1299374	NM_177924.5(ASAH1):c.427T>G (p.Cys143Gly)	Pathogenic
1299375	NM_177924.5(ASAH1):c.358G>C (p.Ala120Pro)	Pathogenic
1323476	NM_177924.5(ASAH1):c.885_886del (p.Asp297fs)	Pathogenic
1363975	NM_177924.5(ASAH1):c.61_76del (p.Ala21fs)	Pathogenic
1369094	NM_177924.5(ASAH1):c.456dup (p.Gly153fs)	Pathogenic
1451339	NM_177924.5(ASAH1):c.409_410insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNCGTGTACTCGTGATCCTCCCGCCTCTGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTCATTCAATATTTTTT (p.Tyr137fs)	Pathogenic
1451699	NC_000008.11:g.18061741del	Pathogenic
1451795	NM_177924.5(ASAH1):c.387_388del (p.Glu129fs)	Pathogenic
1454635	NM_177924.5(ASAH1):c.283C>T (p.Gln95Ter)	Pathogenic
1455993	NM_177924.5(ASAH1):c.1048_1049del (p.Ser350fs)	Pathogenic
1457179	NC_000008.10:g.(?17941470)(17941567_?)del	Pathogenic
1459650	NM_177924.5(ASAH1):c.64C>T (p.Gln22Ter)	Pathogenic
145968	GRCh38/hg38 8p23.1-21.3(chr8:12732530-20436882)x3	Pathogenic
180642	NM_177924.5(ASAH1):c.850G>T (p.Gly284Ter)	Pathogenic
180643	NM_177924.5(ASAH1):c.456A>C (p.Lys152Asn)	Pathogenic
1956640	NM_177924.5(ASAH1):c.663_666del (p.Leu221_Thr222insTer)	Pathogenic
2025980	NM_177924.5(ASAH1):c.125+1G>T	Pathogenic
2044222	NM_177924.5(ASAH1):c.455_456del (p.Lys152fs)	Pathogenic
2069383	NM_177924.5(ASAH1):c.185G>A (p.Trp62Ter)	Pathogenic
2088721	NM_177924.5(ASAH1):c.208del (p.Ala70fs)	Pathogenic
2103233	NM_177924.5(ASAH1):c.952C>T (p.Gln318Ter)	Pathogenic
2195338	NM_177924.5(ASAH1):c.931C>T (p.Gln311Ter)	Pathogenic
2413836	NM_177924.5(ASAH1):c.177C>A (p.Tyr59Ter)	Pathogenic
2696690	NM_177924.5(ASAH1):c.621T>A (p.Tyr207Ter)	Pathogenic
2703279	NM_177924.5(ASAH1):c.744G>A (p.Trp248Ter)	Pathogenic
2743733	NM_177924.5(ASAH1):c.53dup (p.Cys18fs)	Pathogenic
2770814	NM_177924.5(ASAH1):c.1042_1045del (p.Asn348fs)	Pathogenic
2855734	NM_177924.5(ASAH1):c.340G>T (p.Glu114Ter)	Pathogenic
2913835	NM_177924.5(ASAH1):c.1_2delinsCG (p.Met1Arg)	Pathogenic

SpliceAI

2042 predictions. Top by Δscore:

Variant	Effect	Δscore
8:18058830:AATAC:A	donor_loss	1.0000
8:18058831:ATACC:A	donor_loss	1.0000
8:18058832:TAC:T	donor_loss	1.0000
8:18058833:A:C	donor_loss	1.0000
8:18058834:C:T	donor_loss	1.0000
8:18058888:TATT:T	acceptor_gain	1.0000
8:18058888:TATTC:T	acceptor_loss	1.0000
8:18058890:TT:T	acceptor_gain	1.0000
8:18058890:TTCT:T	acceptor_loss	1.0000
8:18058891:TCT:T	acceptor_loss	1.0000
8:18058892:C:CC	acceptor_gain	1.0000
8:18058892:C:G	acceptor_loss	1.0000
8:18058893:T:C	acceptor_loss	1.0000
8:18059465:C:CC	acceptor_gain	1.0000
8:18059566:A:AC	donor_gain	1.0000
8:18059567:C:CC	donor_gain	1.0000
8:18059567:CTTA:C	donor_gain	1.0000
8:18059570:A:AC	donor_gain	1.0000
8:18059571:C:CT	donor_gain	1.0000
8:18059571:CT:C	donor_gain	1.0000
8:18059571:CTCA:C	donor_gain	1.0000
8:18059581:T:TA	donor_gain	1.0000
8:18059590:T:TA	donor_gain	1.0000
8:18059699:CATAA:C	acceptor_gain	1.0000
8:18059700:ATAA:A	acceptor_gain	1.0000
8:18059701:TAA:T	acceptor_gain	1.0000
8:18059702:AA:A	acceptor_gain	1.0000
8:18059702:AAC:A	acceptor_loss	1.0000
8:18059703:AC:A	acceptor_loss	1.0000
8:18059704:C:CC	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000057430 (8:18084869 G>A,C,T), RS1000066908 (8:18068492 G>A), RS1000102956 (8:18079034 T>G), RS1000246630 (8:18084083 C>G,T), RS1000438746 (8:18061582 T>C), RS1000669062 (8:18067527 C>G,T), RS1000723723 (8:18062485 G>A,C,T), RS1000732376 (8:18066421 C>A,T), RS1000935424 (8:18057720 GTTAT>G), RS1000977871 (8:18075285 G>A,C), RS1001015066 (8:18064076 G>A,C), RS1001121064 (8:18084442 G>A,C,T), RS1001230553 (8:18077657 G>A,T), RS1001321879 (8:18075356 T>C), RS1001329917 (8:18059224 G>A,C,T)

Disease associations

OMIM: gene MIM:613468 | disease phenotypes: MIM:228000, MIM:159950, MIM:117100, MIM:148100, MIM:617468, MIM:208150

GenCC curated gene-disease

Disease	Classification	Inheritance
spinal muscular atrophy-progressive myoclonic epilepsy syndrome	Definitive	Autosomal recessive
Farber lipogranulomatosis	Definitive	Autosomal recessive
ASAH1-related disorders	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ASAH1-related sphingolipidosis	Definitive	AR

Mondo (10): Farber lipogranulomatosis (MONDO:0009218), spinal muscular atrophy-progressive myoclonic epilepsy syndrome (MONDO:0008045), congenital nervous system disorder (MONDO:0002320), breast ductal adenocarcinoma (MONDO:0005590), self-limited epilepsy with centrotemporal spikes (MONDO:0007295), ASAH1-related sphingolipidosis (MONDO:0100524), keloid formation (MONDO:0007847), arthrogryposis multiplex congenita (MONDO:0015168), fetal akinesia deformation sequence 1 (MONDO:0100101), (MONDO:0800460)

Orphanet (5): Farber disease (Orphanet:333), Spinal muscular atrophy-progressive myoclonic epilepsy syndrome (Orphanet:2590), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), Arthrogryposis multiplex congenita (Orphanet:1037), Fetal akinesia deformation sequence (Orphanet:994)

HPO phenotypes

123 total (30 of 123 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000502	Abnormal conjunctiva morphology
HP:0000608	Macular degeneration
HP:0000639	Nystagmus
HP:0000707	Abnormality of the nervous system
HP:0000708	Atypical behavior
HP:0000726	Dementia
HP:0000737	Irritability
HP:0000766	Abnormal sternum morphology
HP:0000939	Osteoporosis
HP:0001155	Abnormality of the hand
HP:0001187	Hyperextensibility of the finger joints
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001268	Mental deterioration
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001308	Tongue fasciculations
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001369	Arthritis
HP:0001371	Flexion contracture
HP:0001386	Joint swelling
HP:0001395	Hepatic fibrosis
HP:0001399	Hepatic failure
HP:0001433	Hepatosplenomegaly

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001057_11	Obesity	4.000000e-07
GCST001057_12	Obesity	2.000000e-07
GCST001057_9	Obesity	8.000000e-08
GCST003542_5	Night sleep phenotypes	3.000000e-06
GCST004297_6	Atrial fibrillation	6.000000e-10
GCST006061_67	Atrial fibrillation	2.000000e-19
GCST006061_68	Atrial fibrillation	4.000000e-18
GCST006414_129	Atrial fibrillation	2.000000e-21
GCST010118_159	Type 2 diabetes	2.000000e-09

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D055577	Farber Lipogranulomatosis	C10.228.140.163.100.435.825.250; C16.320.565.189.435.825.250; C16.320.565.398.641.803.325; C16.320.565.595.554.825.250; C18.452.132.100.435.825.250; C18.452.584.563.641.803.325; C18.452.648.189.435.825.250; C18.452.648.398.641.803.325; C18.452.648.595.554.825.250
C537563	Jankovic Rivera syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5463 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 39,644 (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
CHEMBL460499	CARMOFUR	2	39,644

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Acid ceramidase

Binding affinities (BindingDB)

60 measured of 61 human assays (61 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-oxo-4-phenyl-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	0.8 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
4-fluoro-2-oxo-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	1 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
5-nitro-2-oxo-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	3 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
6-nitro-2-oxo-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	3 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
5-chloro-2-oxo-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	9 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
6-fluoro-2-oxo-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	10 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
2-oxo-N-(4-phenylbutyl)-5- (trifluoromethyl)-1,3- benzoxazole-3-carboxamide	IC50	11 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
5-cyano-2-oxo-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	11 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
2-methylpropyl 5-bromo-3-(hexylcarbamoyl)-2,6-dioxo-5H-pyrimidin-3-ium-1-carboxylate	IC50	14 nM	US-9428465: Acid ceramidase inhibitors and their use as medicaments
6-(4-chlorobenzoyl)-2-oxo-N- (4-phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	14 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
2-oxo-N-(4-phenylbutyl)-6- propanoyl-1,3-benzoxazole- 3-carboxamide	IC50	16 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
5,6-dichloro-2-oxo-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	18 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
7-bromo-2-oxo-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	18 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
2-oxo-N-[(4- propylphenyl)methyl]-1,3- benzoxazole-3-carboxamide	IC50	19 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
2-oxo-N-(4-phenylbutyl)-6- (trifluoromethyl)-1,3- benzoxazole-3-carboxamide	IC50	20 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
5-bromo-2-oxo-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	22 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
2-oxo-5-phenyl-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	22 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
7-methyl-2-oxo-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	23 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
6-(4-methoxybenzoyl)-2-oxo- N-(5-phenylpentyl)-1,3- benzoxazole-3-carboxamide	IC50	26 nM	US-10213416
2-oxo-N-[4-(p-tolyl)butyl]- 1,3-benzoxazole-3- carboxamide	IC50	28 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
6-benzoyl-2-oxo-N-(4-phenyl- butyl)-1,3-benzoxazole-3- carboxamide	IC50	29 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
6-chloro-2-oxo-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	33 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
6-bromo-2-oxo-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	33 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
N-octyl-2-oxo-1,3- benzoxazole-3-carboxamide	IC50	34 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
5-bromo-N-hexyl-2,4-dioxopyrimidine-1-carboxamide	IC50	35 nM	US-9428465: Acid ceramidase inhibitors and their use as medicaments
5-chloro-7-(4-fluorophenyl)-2- oxo-N-(5-phenylpentyl)-1,3- benzoxazole-3-carboxamide	IC50	37 nM	US-10213416
5-(4-methoxybenzoyl)-2-oxo- N-(6-phenylhexyl)-1,3- benzoxazole-3-carboxamide	IC50	46 nM	US-10213416
N-[3-(3-fluorophenyl)propyl]- 2-oxo-1,3-benzoxazole-3- carboxamide	IC50	49 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
N-heptyl-2-oxo-1,3- benzoxazole-3-carboxamide	IC50	50 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
6-methoxy-2-oxo-N-(4- phenyl-butyl)-1,3- benzoxazole-3-carboxamide	IC50	52 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
2-oxo-N-(5-phenylpentyl)- 1,3-benzoxazole-3- carboxamide	IC50	54 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
2-oxo-N-(3-phenylpropyl)- 1,3-benzoxazole-3- carboxamide	IC50	55 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
5-fluoro-2-oxo-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	56 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
5-(4-fluorophenyl)-2-oxo-N- (4-phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	56 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
N-[4-(2-naphthyl)butyl]-2- oxo-1,3-benzoxazole-3- carboxamide	IC50	57 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
N-(4-cyclohexylbutyl)-2-oxo- 1,3-benzoxazole-3- carboxamide	IC50	62 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
N-[4-(4- methoxyphenyl)butyl]-2-oxo- 1,3-benzoxazole-3- carboxamide	IC50	63 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
2-oxo-N-(4-phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	64 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
7-(4-fluorobenzoyl)-2-oxo-N- (5-phenylpentyl)-1,3- benzoxazole-3-carboxamide	IC50	66 nM	US-10213416
6-methyl-2-oxo-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	66 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
6-(4-methoxyphenyl)-2-oxo- N-(4-phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	67 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
5-(4-methoxyphenyl)-2-oxo- N-(4-phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	68 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
6-(4-fluorophenyl)-2-oxo-N-(5- phenylpentyl)-1,3- benzoxazole-3-carboxamide	IC50	75 nM	US-10213416
N-[4-(4-fluorophenyl)butyl]- 2-oxo-1,3-benzoxazole-3- carboxamide	IC50	75 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
6-(4-fluorophenyl)-2-oxo-N- (4-phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	79 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
2-oxo-6-phenyl-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	84 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
2-oxo-7-phenyl-N-(4- phenylbutyl)-1,3- benzoxazole-3-carboxamide	IC50	91 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
2-oxo-N-[4-(2-thienyl)butyl]- 1,3-benzoxazole-3- carboxamide	IC50	99 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
2-oxo-N-(6-phenylhexyl)-1,3- benzoxazole-3-carboxamide	IC50	99 nM	US-10226452: Benzoxazolone derivatives as acid ceramidase inhibitors, and their use as medicaments
6-(2-fluorophenyl)-2-oxo-N-(5- phenylpentyl)-1,3- benzoxazole-3-carboxamide	IC50	102 nM	US-10213416

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
9.10	IC50	0.8	nM	CHEMBL3741996
9.05	IC50	0.9	nM	CHEMBL4093029
9.00	IC50	1	nM	CHEMBL4103207
8.89	IC50	1.3	nM	CHEMBL4084295
8.68	IC50	2.1	nM	CHEMBL4092051
8.66	IC50	2.2	nM	CHEMBL4062592
8.62	IC50	2.4	nM	CHEMBL4065362
8.62	IC50	2.4	nM	CHEMBL4075447
8.60	IC50	2.5	nM	CHEMBL4100744
8.52	IC50	3	nM	CHEMBL3741624
8.52	IC50	3	nM	CHEMBL3741606
8.52	IC50	3	nM	CHEMBL4580541
8.39	IC50	4.1	nM	CHEMBL4071239
8.33	IC50	4.7	nM	CHEMBL4075028
8.30	IC50	5	nM	CHEMBL4742096
8.22	IC50	6	nM	CHEMBL4592427
8.18	IC50	6.6	nM	CHEMBL66205
8.15	IC50	7	nM	CHEMBL4089655
8.15	IC50	7	nM	CHEMBL4096883
8.11	IC50	7.7	nM	CHEMBL2333055
8.08	IC50	8.3	nM	CHEMBL4076230
8.07	IC50	8.5	nM	CHEMBL4101140
8.00	IC50	9.9	nM	CHEMBL4095461
7.92	IC50	12	nM	CHEMBL3741732
7.89	IC50	12.8	nM	CHEMBL4777626
7.86	IC50	13.9	nM	CHEMBL4094489
7.85	IC50	14	nM	CHEMBL3740891
7.85	IC50	14	nM	CHEMBL3900210
7.85	IC50	14	nM	CHEMBL4754069
7.83	IC50	14.8	nM	CHEMBL4075846
7.82	IC50	15	nM	CHEMBL3740027
7.75	IC50	18	nM	CHEMBL3739503
7.75	IC50	18	nM	CHEMBL3739921
7.75	IC50	18	nM	CHEMBL3741563
7.75	IC50	18	nM	CHEMBL4777275
7.72	IC50	19	nM	CHEMBL3741565
7.70	IC50	20	nM	CHEMBL3741712
7.68	IC50	21	nM	CHEMBL4099796
7.68	IC50	20.7	nM	CARMOFUR
7.66	IC50	22	nM	CHEMBL3740148
7.65	IC50	22.5	nM	CHEMBL4076865
7.64	IC50	23	nM	CHEMBL3742201
7.62	IC50	24	nM	CHEMBL3739808
7.62	IC50	24	nM	CHEMBL4461146
7.60	IC50	25	nM	CHEMBL3739956
7.60	IC50	25	nM	CHEMBL4753638
7.60	IC50	25	nM	CHEMBL4783041
7.58	IC50	26	nM	CHEMBL5774662
7.54	IC50	29	nM	CHEMBL3740970
7.54	IC50	29	nM	CARMOFUR

PubChem BioAssay actives

167 with measured affinity, of 407 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-oxo-4-phenyl-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0008	uM
2-amino-N-(4-phenylbutyl)benzimidazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0009	uM
2-methyl-N-(4-phenylbutyl)benzimidazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0010	uM
N-(4-phenylbutyl)triazolo[4,5-b]pyridine-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0013	uM
N-(4-phenylbutyl)benzotriazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0021	uM
N-hexyltriazolo[4,5-b]pyridine-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0022	uM
2-amino-N-hexylbenzimidazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0024	uM
1,3-dioxo-N-(4-phenylbutyl)isoindole-2-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0024	uM
N-(4-phenylbutyl)benzimidazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0025	uM
5-nitro-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0030	uM
6-nitro-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0030	uM
2-oxo-N-(4-phenylbutyl)-[1,3]oxazolo[5,4-c]pyridine-1-carboxamide	1547373: Inhibition of human acid ceramidase expressed in HEK293 cells using Rbm14-12 as substrate preincubated for 10 mins followed by substrate addition and measured after 3 hrs by fluorescence assay	ic50	0.0030	uM
N-hexylbenzotriazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0041	uM
N-(4-phenylbutyl)indazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0047	uM
4-(4-chlorophenyl)-2-oxo-N-(4-phenylbutyl)-1,3-oxazole-3-carboxamide	1707275: Inhibition of human acid ceramidase using N-lauroyl ceramide incubated for 1 hr by LC/MS analysis	ic50	0.0050	uM
2-oxo-N-(4-phenylbutyl)-[1,3]oxazolo[4,5-c]pyridine-3-carboxamide	1547373: Inhibition of human acid ceramidase expressed in HEK293 cells using Rbm14-12 as substrate preincubated for 10 mins followed by substrate addition and measured after 3 hrs by fluorescence assay	ic50	0.0060	uM
N-hexylbenzimidazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0066	uM
N-hexyl-1,3-dioxoisoindole-2-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0070	uM
2-amino-N-[(4-methylphenyl)methyl]benzimidazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0070	uM
2-methylpropyl 5-fluoro-3-(hexylcarbamoyl)-2,6-dioxopyrimidine-1-carboxylate	1707268: Inhibition of human acid ceramidase	ic50	0.0077	uM
N-[(3-methylphenyl)methyl]benzimidazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0083	uM
2-amino-N-[(3-methylphenyl)methyl]benzimidazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0085	uM
N-hexylindazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0099	uM
5-fluoro-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0120	uM
2-methylpropyl 5-chloro-3-(hexylcarbamoyl)-2,6-dioxopyrimidine-1-carboxylate	1707268: Inhibition of human acid ceramidase	ic50	0.0128	uM
2-methoxy-N-(4-phenylbutyl)benzimidazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0139	uM
6-(4-chlorobenzoyl)-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0140	uM
N-hexyl-3-methyl-5-(trifluoromethyl)pyrazole-1-carboxamide	1707268: Inhibition of human acid ceramidase	ic50	0.0140	uM
N-[(4-methylphenyl)methyl]benzimidazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0148	uM
5-chloro-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0150	uM
7-bromo-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0180	uM
5,6-dichloro-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0180	uM
2-oxo-N-(4-phenylbutyl)-5-(trifluoromethyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0180	uM
2-oxo-N-(4-phenylbutyl)-5-pyridin-4-yl-1,3-oxazole-3-carboxamide	1707275: Inhibition of human acid ceramidase using N-lauroyl ceramide incubated for 1 hr by LC/MS analysis	ic50	0.0180	uM
2-oxo-N-[(4-propylphenyl)methyl]-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0190	uM
2-oxo-N-(4-phenylbutyl)-6-(trifluoromethyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0200	uM
5-fluoro-N-hexyl-2,4-dioxopyrimidine-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0207	uM
2-oxo-1-N,3-N-bis(4-phenylbutyl)benzimidazole-1,3-dicarboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0210	uM
5-bromo-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0220	uM
N-benzylbenzimidazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0225	uM
7-methyl-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0230	uM
5-benzoyl-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0240	uM
5-fluoro-6-(1-methylpiperidin-4-yl)-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1547373: Inhibition of human acid ceramidase expressed in HEK293 cells using Rbm14-12 as substrate preincubated for 10 mins followed by substrate addition and measured after 3 hrs by fluorescence assay	ic50	0.0240	uM
N-[4-(4-methylphenyl)butyl]-2-oxo-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0250	uM
2-oxo-N-pentyl-4-phenyl-1,3-oxazole-3-carboxamide	1707275: Inhibition of human acid ceramidase using N-lauroyl ceramide incubated for 1 hr by LC/MS analysis	ic50	0.0250	uM
2-oxo-N-(4-phenylbutyl)-5-pyridin-2-yl-1,3-oxazole-3-carboxamide	1707275: Inhibition of human acid ceramidase using N-lauroyl ceramide incubated for 1 hr by LC/MS analysis	ic50	0.0250	uM
6-benzoyl-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0290	uM
2-amino-N-benzylbenzimidazole-1-carboxamide	1445366: Inhibition of human C-terminal His-tagged acid ceramidase variant 1 expressed in HEK293 cells using fluorogenic substrate Rbm-14-12 preincubated for 30 mins followed by substrate addition measured after 1 hr by fluorogenic assay	ic50	0.0293	uM
6-fluoro-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0310	uM
6-bromo-2-oxo-N-(4-phenylbutyl)-1,3-benzoxazole-3-carboxamide	1265564: Inhibition of recombinant human acid ceramidase expressed in HEK293 cells using N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)-4-(2-oxochromen-7-yl)-oxybutyl]dodecanamide substrate preincubated for 10 mins	ic50	0.0310	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, decreases methylation, increases expression	6
Valproic Acid	affects expression, decreases methylation, increases expression	5
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance, increases expression	4
Amitriptyline	increases expression	3
Tamoxifen	increases expression	3
Arsenic Trioxide	increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	2
Amiodarone	increases expression	2
trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride	increases expression	2
Benzo(a)pyrene	increases mutagenesis, affects methylation	2
Clozapine	increases expression	2
Flecainide	increases expression	2
Fluorouracil	affects response to substance, affects reaction, decreases expression	2
Fluoxetine	increases expression	2
Imipramine	increases expression	2
Perhexiline	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Smoke	decreases expression, increases abundance	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
Zimeldine	increases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
apocarotenal	increases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
beta-lapachone	increases expression	1
manganese chloride	increases abundance, increases expression	1
sulindac sulfide	decreases expression	1

ChEMBL screening assays

111 unique, capped per target: 108 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1022222	Binding	Inhibition of acid ceramidase in human MCF7 cell lysate at 50 uM by scintillation counting	Synthesis and bioevaluation of omega-N-amino analogs of B13. — Bioorg Med Chem
CHEMBL5723203	Functional	Affinity Biochemical interaction: (inhibition of substrate hydrolysis determined through mass spectrometry) EUB0002527a ASAH1	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

13 cell lines: 6 finite cell line, 4 cancer cell line, 2 induced pluripotent stem cell, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_8A65	GM02315	Finite cell line	Female
CVCL_8A69	GM20015	Finite cell line	Male
CVCL_8A70	GM20016	Finite cell line	Female
CVCL_8A71	GM20017	Finite cell line	Male
CVCL_8A72	GM20018	Finite cell line	Female
CVCL_8A73	GM20019	Finite cell line	Female
CVCL_A8PD	TRNDi030-A	Induced pluripotent stem cell	Male
CVCL_B7W1	Abcam Raji ASAH1 KO	Cancer cell line	Male
CVCL_B9WJ	Abcam THP-1 ASAH1 KO	Cancer cell line	Male
CVCL_C0KA	AIW002-02/ASAH1-KO	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03490487	PHASE4	UNKNOWN	Electroclinical Effect of Steroid in Patients With Benign Childhood Epilepsy With Centrotemporal Spikes
NCT04610879	PHASE4	TERMINATED	Changing Agendas on Sleep, Treatment and Learning in Epilepsy
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT03233841	Not specified	COMPLETED	Farber Disease Natural History Study
NCT07173010	Not specified	NOT_YET_RECRUITING	Pediatric Arthropathy Beyond Inflammation: Clinical Spectrum and Diagnostic Approach at Assiut University Children Hospital
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery
NCT01046760	Not specified	UNKNOWN	Scholar Performance and Praxis Assessment in Children With Rolandic Epilepsy
NCT01335425	Not specified	COMPLETED	The Rolandic Epilepsy/ESES/Landau-Kleffner Syndrome and Correlation With Language Impairment Study
NCT01515436	Not specified	COMPLETED	The Effect of Music Periodicity on Interictal Epileptiform Discharges
NCT03465566	Not specified	UNKNOWN	Emotion Recognition in Benign Epilepsy of Childhood With Centro-Temporal Spikes (BECTS)
NCT03547050	Not specified	COMPLETED	Rolandic Epilepsy Genomewide Association International Study
NCT03865771	Not specified	RECRUITING	Sleep Related Memory Consolidation in Children With Age Related Focal Epilepsy.
NCT04325282	Not specified	COMPLETED	Transcranial Magnetic Stimulation for BECTS
NCT04357236	Not specified	COMPLETED	18F-FDG PET Imaging Analysis of Antiepileptic Drug Response in BECTS
NCT04569708	Not specified	COMPLETED	Sleep Spindles and Memory in Rolandic Epilepsy
NCT06545708	Not specified	RECRUITING	Music Perception in SeLECTs
NCT05393375	Not specified	COMPLETED	Arthrogryposis Multiplex Congenita in Pediatric Age: Correlation Between MUScular MRI and Functional Evaluation
NCT05673265	Not specified	UNKNOWN	Pediatric and Adult Registry for Patients With ARThrogryposis
NCT06130592	Not specified	UNKNOWN	Technical Feasibility Study of Ultrasound Muscle Imaging in Antenatal Ultrasound
NCT07360574	Not specified	NOT_YET_RECRUITING	Piezo2-related Arthrogryposis & physiopathOLOgy 3