ASAH2

Summary

ASAH2 (N-acylsphingosine amidohydrolase 2, HGNC:18860) is a protein-coding gene on chromosome 10q11.23, encoding Neutral ceramidase (Q9NR71). Plasma membrane ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral pH.

Ceramidases (EC 3.5.1.23), such as ASAH2, catalyze hydrolysis of the N-acyl linkage of ceramide, a second messenger in a variety of cellular events, to produce sphingosine. Sphingosine exerts both mitogenic and apoptosis-inducing activities, and its phosphorylated form functions as an intra- and intercellular second messenger (see MIM 603730) (Mitsutake et al., 2001 [PubMed 11328816]).

Source: NCBI Gene 56624 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 45 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_019893

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18860
Approved symbol	ASAH2
Name	N-acylsphingosine amidohydrolase 2
Location	10q11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000188611
Ensembl biotype	protein_coding
OMIM	611202
Entrez	56624

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 nonsense_mediated_decay

ENST00000329428, ENST00000395526, ENST00000443575, ENST00000474434, ENST00000489640, ENST00000682911

RefSeq mRNA: 2 — MANE Select: NM_019893 NM_001143974, NM_019893

CCDS: CCDS7239

Canonical transcript exons

ENST00000682911 — 21 exons

Exon	Start	End
ENSE00001371062	50245222	50245454
ENSE00001382334	50243202	50243351
ENSE00002435460	50235888	50236064
ENSE00002440710	50214743	50214868
ENSE00002454332	50203640	50203679
ENSE00002457657	50233184	50233261
ENSE00002468012	50234425	50234552
ENSE00002471188	50218510	50218630
ENSE00002472589	50210823	50210904
ENSE00002475746	50202829	50202924
ENSE00002479064	50212972	50213058
ENSE00002487543	50211030	50211134
ENSE00002504063	50205982	50206097
ENSE00002514027	50204861	50204955
ENSE00003543627	50196773	50196919
ENSE00003702819	50192653	50192712
ENSE00003707466	50199051	50199146
ENSE00003708352	50189499	50189587
ENSE00003860843	50248484	50248646
ENSE00003918819	50251395	50251516
ENSE00003920510	50184861	50187504

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 97.06.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7319 / max 609.9951, expressed in 32 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109344	0.6996	22
109346	0.0206	7
109345	0.0117	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	97.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.60	gold quality
stromal cell of endometrium	CL:0002255	71.16	gold quality
islet of Langerhans	UBERON:0000006	70.59	gold quality
adrenal tissue	UBERON:0018303	66.96	gold quality
smooth muscle tissue	UBERON:0001135	66.60	gold quality
ganglionic eminence	UBERON:0004023	66.18	gold quality
endometrium	UBERON:0001295	64.86	gold quality
pancreas	UBERON:0001264	64.65	gold quality
hindlimb stylopod muscle	UBERON:0004252	64.53	gold quality
tonsil	UBERON:0002372	64.51	gold quality
muscle tissue	UBERON:0002385	64.36	gold quality
skeletal muscle tissue	UBERON:0001134	64.32	gold quality
liver	UBERON:0002107	64.25	gold quality
fundus of stomach	UBERON:0001160	63.99	gold quality
cortical plate	UBERON:0005343	63.92	gold quality
calcaneal tendon	UBERON:0003701	63.79	gold quality
ventricular zone	UBERON:0003053	63.63	gold quality
rectum	UBERON:0001052	63.41	gold quality
small intestine	UBERON:0002108	62.80	gold quality
stomach	UBERON:0000945	62.62	gold quality
mucosa of stomach	UBERON:0001199	62.42	gold quality
lower esophagus mucosa	UBERON:0035834	62.06	gold quality
primary visual cortex	UBERON:0002436	61.77	gold quality
body of stomach	UBERON:0001161	61.16	gold quality
body of pancreas	UBERON:0001150	61.08	gold quality
colonic epithelium	UBERON:0000397	61.01	gold quality
prefrontal cortex	UBERON:0000451	60.78	gold quality
vermiform appendix	UBERON:0001154	60.54	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.93

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, GATA2, HNF4A, JUN, NR3C1

Literature-anchored findings (GeneRIF, showing 14)

• Blocking acid ceramidase but not sphingosine kinase activity in alveolar macrophages led to decreased ERK and Akt activity and induction of cell death. (PMID:15210766)
• Neutral ceramidase is localized mainly in plasma membranes. (PMID:15845354)
• the present study identified a novel amidase sequence containing a critical serine residue that may function as a nucleophile in the hydrolytic attack on the amide bond present in ceramide (PMID:16229686)
• Important for the generation of sphgosine 1 phosphqte (S1P) and S1P-mediated cell proliferation and survival. (PMID:16940153)
• the purification and characterization of neutral ceramidase from human ileostomy content, using octanoyl-[(14)C]sphingosine as substrate (PMID:17475390)
• serine palmitoyltransferase and ceramidase are two major ceramide metabolizing enzymes that may have roles in psoriatic epidermis (PMID:17982236)
• 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)
• c-Jun/AP-1 signaling may, in part, regulate serum-induced nCDase gene transcription (PMID:21530485)
• cloned a 3000 bp region upstream of the translational start site of the nCDase gene (PMID:21531200)
• These results demonstrate for the first time that adiponectin inhibits TNFalpha-induced inflammatory response via Cav1-mediated ceramidase recruitment and activation in an AdipoR1-dependent fashion. (PMID:24397980)
• The structural basis for ceramide recognition and hydrolysis by human neutral ceramidase has been uncovered. (PMID:26190575)
• Neutral ceramidase: Advances in mechanisms, cell regulation, and roles in cancer. (PMID:30389354)
• Asah2 Represses the p53-Hmox1 Axis to Protect Myeloid-Derived Suppressor Cells from Ferroptosis. (PMID:33547170)
• Measurement of neutral ceramidase activity in vitro and in vivo. (PMID:35134389)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	asah2	ENSDARG00000012829
mus_musculus	Asah2	ENSMUSG00000024887
rattus_norvegicus	Asah2	ENSRNOG00000012196
drosophila_melanogaster	CDase	FBGN0039774

Paralogs (1): ASAH2B (ENSG00000204147)

Protein

Protein identifiers

Neutral ceramidase — Q9NR71 (reviewed: Q9NR71)

Alternative names: Acylsphingosine deacylase 2, BCDase, LCDase, N-acylsphingosine amidohydrolase 2, Non-lysosomal ceramidase

All UniProt accessions (5): A0A0C4DFQ8, E9PBM9, Q9NR71, V9GY52, V9GYJ5

UniProt curated annotations — full annotation on UniProt →

Function. Plasma membrane ceramidase that hydrolyzes sphingolipid ceramides into sphingosine and free fatty acids at neutral 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. Also catalyzes the reverse reaction allowing the synthesis of ceramides from fatty acids and sphingosine. Together with sphingomyelinase, participates in the production of sphingosine and sphingosine-1-phosphate from the degradation of sphingomyelin, a sphingolipid enriched in the plasma membrane of cells. Also participates in the hydrolysis of ceramides from the extracellular milieu allowing the production of sphingosine-1-phosphate inside and outside cells. This is the case for instance with the digestion of dietary sphingolipids in the intestinal tract.

Subcellular location. Cell membrane. Membrane raft. Membrane. Caveola. Golgi apparatus membrane. Mitochondrion. Secreted. Extracellular exosome Secreted.

Tissue specificity. Primarily expressed in intestine. Ubiquitously expressed with higher levels in kidney, skeletal muscle and heart. The ubiquitous expression observed for ASAH2 might be an experimental artifact due to the paralog ASAH2B.

Post-translational modifications. Proteolytic cleavage of the N-terminus removes the signal-anchor and produces a soluble form of the protein. N-glycosylated. Required for enzyme activity. O-glycosylated. Required to retain it as a type II membrane protein at the cell surface. Phosphorylated. May prevent ubiquitination and subsequent degradation. Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is triggered by nitric oxide.

Activity regulation. Inhibited by dithiothreitol (DTT) and 2-mercaptoethanol. Activity is mildly stimulated by Ca(2+) and Mg(2+), but is not inhibited by EDTA. Activity is inhibited by millimolar levels of Fe(2+), Zn(2+) and Cu(2+). Inhibited by cholesterol.

Cofactor. Binds 1 zinc ion per subunit.

Induction. Down-regulated by gemcitabine/GMZ (at protein level). Down-regulated upon serum starvation.

Pathway. Lipid metabolism; sphingolipid metabolism.

Similarity. Belongs to the neutral ceramidase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NR71-1	1	yes
Q9NR71-2	2

RefSeq proteins (2): NP_001137446, NP_063946* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006823	Ceramidase_alk	Family
IPR031329	NEUT/ALK_ceramidase_N	Domain
IPR031331	NEUT/ALK_ceramidase_C	Domain
IPR038445	NCDase_C_sf	Homologous_superfamily

Pfam: PF04734, PF17048

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), 11 shown:

• an N-acylsphing-4-enine + H2O = sphing-4-enine + a fatty acid (RHEA:20856)
• N-hexadecanoylsphing-4-enine + H2O = sphing-4-enine + hexadecanoate (RHEA:38891)
• N-(15Z-tetracosenoyl)-sphing-4-enine + H2O = (15Z)-tetracosenoate + sphing-4-enine (RHEA:41267)
• 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)
• sphinganine + hexadecanoate = N-hexadecanoylsphinganine + H2O (RHEA:43440)
• N-(octadecanoyl)-sphinganine + H2O = sphinganine + octadecanoate (RHEA:45008)
• N-octanoylsphing-4-enine + H2O = octanoate + sphing-4-enine (RHEA:45092)

UniProt features (125 total): strand 38, glycosylation site 21, helix 18, mutagenesis site 18, binding site 8, turn 3, disulfide bond 3, sequence conflict 3, chain 2, topological domain 2, sequence variant 2, region of interest 2, site 1, transmembrane region 1, splice variant 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4WGK	X-RAY DIFFRACTION	2.58

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NR71-F1	91.24	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): 98–99 (cleavage); 354 (nucleophile)

Ligand- & substrate-binding residues (8): 194; 303; 540; 579; 712; 714; 717; 134

Disulfide bonds (3): 362–376, 369–384, 448–498

Glycosylation sites (21): 62, 67, 68, 70, 73, 74, 76, 78, 79, 80, 82, 84, 98, 151, 217, 308, 440, 468, 564, 730 …

Mutagenesis-validated functional residues (18):

Position	Phenotype
124	loss of ceramide hydrolase activity.
194	loss of ceramide hydrolase activity.
196	loss of ceramide hydrolase activity.
211	loss of ceramide hydrolase activity.
257	loss of ceramide hydrolase activity.
258	decreased ceramide hydrolase activity.
303	loss of ceramide hydrolase activity.
352	loss of ceramide hydrolase activity.
354	loss of ceramide hydrolase activity.
362	loss of ceramide hydrolase activity.
374	decreased ceramide hydrolase activity.
396	no effect on ceramide hydrolase activity.
465	loss of ceramide hydrolase activity.
540	loss of ceramide hydrolase activity.
579	loss of ceramide hydrolase activity.
591	loss of ceramide hydrolase activity.
595	decreased ceramide hydrolase activity.
729	decreased ceramide hydrolase activity.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9840310	Glycosphingolipid catabolism
R-HSA-1430728	Metabolism
R-HSA-1660662	Glycosphingolipid metabolism
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 147 (showing top): GOBP_CERAMIDE_CATABOLIC_PROCESS, GOBP_DIGESTION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_RESPONSE_TO_PEPTIDE, GOBP_POLYOL_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_LONG_CHAIN_FATTY_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_DIGESTION, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, CEBP_Q2, GOBP_SPHINGOID_METABOLIC_PROCESS

GO Biological Process (13): sphingosine metabolic process (GO:0006670), ceramide metabolic process (GO:0006672), apoptotic process (GO:0006915), regulation of mitotic cell cycle (GO:0007346), long-chain fatty acid biosynthetic process (GO:0042759), lipid digestion (GO:0044241), sphingosine biosynthetic process (GO:0046512), ceramide biosynthetic process (GO:0046513), ceramide catabolic process (GO:0046514), cellular response to cytokine stimulus (GO:0071345), negative regulation of apoptotic signaling pathway (GO:2001234), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665)

GO Molecular Function (5): calcium ion binding (GO:0005509), zinc ion binding (GO:0008270), N-acylsphingosine amidohydrolase activity (GO:0017040), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (10): Golgi membrane (GO:0000139), extracellular region (GO:0005576), mitochondrion (GO:0005739), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), caveola (GO:0005901), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), membrane (GO:0016020), membrane raft (GO:0045121)

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
cellular anatomical structure	3
apoptotic signaling pathway	2
ceramide metabolic process	2
cytoplasm	2
intracellular membrane-bounded organelle	2
diol metabolic process	1
sphingoid metabolic process	1
sphingolipid metabolic process	1
programmed cell death	1
execution phase of apoptosis	1
mitotic cell cycle	1
regulation of cell cycle	1
long-chain fatty acid metabolic process	1
fatty acid biosynthetic process	1
digestion	1
sphingosine metabolic process	1
diol biosynthetic process	1
sphingoid biosynthetic process	1
sphingolipid biosynthetic process	1
sphingolipid catabolic process	1
response to cytokine	1
negative regulation of signal transduction	1
negative regulation of apoptotic process	1
regulation of apoptotic signaling pathway	1
primary metabolic process	1
lipid metabolic process	1
metal ion binding	1
transition metal ion binding	1
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	1
catalytic activity	1
cation binding	1
Golgi apparatus	1
bounding membrane of organelle	1
endomembrane system	1
membrane	1
cell periphery	1
plasma membrane raft	1
extracellular vesicle	1
intracellular anatomical structure	1
membrane microdomain	1

Protein interactions and networks

STRING

458 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASAH2	ASAH1	Q13510	937
ASAH2	ACER2	Q5QJU3	871
ASAH2	ACER1	Q8TDN7	855
ASAH2	ACER3	Q9NUN7	817
ASAH2	SPTLC1	O15269	773
ASAH2	SMPD2	O60906	747
ASAH2	SPHK2	Q9NRA0	747
ASAH2	SPHK1	Q9NYA1	746
ASAH2	SPTLC2	O15270	721
ASAH2	SPTLC3	Q9NUV7	719
ASAH2	CERK	Q8TCT0	714
ASAH2	ENPP7	Q6UWV6	695
ASAH2	SMPD1	P17405	679
ASAH2	CERS6	Q6ZMG9	670
ASAH2	UGCG	Q16739	645

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ASAH2	MYH3	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): MYH3 (Affinity Capture-MS), MYH4 (Affinity Capture-MS), MYH7 (Affinity Capture-MS), MYH1 (Affinity Capture-MS)

ESM2 similar proteins: A3KPQ7, F4HQM3, F4KHQ8, H1AE13, O06769, O14255, O22585, O64407, O81395, O94680, P10537, P16098, P40345, P82993, P97742, Q05187, Q06K61, Q0INM3, Q0IZZ8, Q0JL46, Q19426, Q22915, Q24451, Q29C43, Q2QRX6, Q304B9, Q54BK2, Q55G11, Q5FWI3, Q5MIX2, Q5W7F1, Q60HF6, Q68Y62, Q7KT91, Q7Y223, Q8L7W8, Q8QGP3, Q8VZR2, Q91XT9, Q93Z24

Diamond homologs: F4HQM3, F4KHQ8, O06769, P0C7U1, Q0JL46, Q29C43, Q304B9, Q54BK2, Q55G11, Q5W7F1, Q91XT9, Q9I596, Q9JHE3, Q9NR71, Q9VA70

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	42
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1707432	GRCh37/hg19 10q11.22-11.23(chr10:49378356-52467181)x1	Pathogenic

SpliceAI

3368 predictions. Top by Δscore:

Variant	Effect	Δscore
10:50187326:CAA:C	donor_gain	1.0000
10:50187385:T:TA	donor_gain	1.0000
10:50187500:AAAAA:A	acceptor_gain	1.0000
10:50187505:C:CC	acceptor_gain	1.0000
10:50189495:TCA:T	donor_loss	1.0000
10:50189496:CA:C	donor_loss	1.0000
10:50189497:A:AC	donor_gain	1.0000
10:50189497:A:C	donor_loss	1.0000
10:50189498:C:CC	donor_gain	1.0000
10:50189583:TGGTT:T	acceptor_gain	1.0000
10:50189586:TTCTG:T	acceptor_loss	1.0000
10:50189588:C:CC	acceptor_gain	1.0000
10:50189589:T:G	acceptor_loss	1.0000
10:50202823:CTTTA:C	donor_loss	1.0000
10:50202824:TTTA:T	donor_loss	1.0000
10:50202824:TTTAC:T	donor_loss	1.0000
10:50202825:TTAC:T	donor_loss	1.0000
10:50202825:TTACC:T	donor_loss	1.0000
10:50202826:TA:T	donor_loss	1.0000
10:50202828:C:T	donor_loss	1.0000
10:50202828:CC:C	donor_loss	1.0000
10:50202922:TTCC:T	acceptor_loss	1.0000
10:50202923:TCCT:T	acceptor_loss	1.0000
10:50202924:CCTA:C	acceptor_loss	1.0000
10:50202925:C:CC	acceptor_gain	1.0000
10:50202925:CT:C	acceptor_loss	1.0000
10:50202926:T:A	acceptor_loss	1.0000
10:50202926:T:G	acceptor_loss	1.0000
10:50203634:A:C	donor_gain	1.0000
10:50203638:A:AC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000060056 (10:50207327 G>A), RS1000068786 (10:50232470 C>T), RS1000122904 (10:50238963 T>C), RS1000182138 (10:50238614 A>G), RS1000297572 (10:50220061 A>G), RS1000336316 (10:50244556 G>A), RS1000413258 (10:50232938 C>T), RS1000418602 (10:50232786 C>A), RS1000424192 (10:50202345 C>T), RS1000476766 (10:50202580 C>T), RS1000508991 (10:50250983 C>A,T), RS1000547526 (10:50246503 A>C,G), RS1000622690 (10:50215408 T>C), RS1000650092 (10:50250310 G>A,C), RS1000659394 (10:50208894 C>T)

Disease associations

OMIM: gene MIM:611202 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001791_38	Urate levels	7.000000e-17
GCST001859_32	Thiazide-induced adverse metabolic effects in hypertensive patients	9.000000e-07
GCST006585_1579	Blood protein levels	5.000000e-73
GCST008478_66	Neurological blood protein biomarker levels	1.000000e-29
GCST008478_67	Neurological blood protein biomarker levels	6.000000e-19
GCST010562_6	Depressive symptoms x herpes simplex 1 infection interaction	2.000000e-07
GCST010562_7	Depressive symptoms x herpes simplex 1 infection interaction	2.000000e-07
GCST012309_6	Schizophrenia	9.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004530	triglyceride measurement
EFO:0007006	depressive symptom measurement
EFO:0007036	herpes virus seropositivity

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2021754 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Neutral ceramidases

ChEMBL bioactivities

6 potent at pChembl≥5 of 7 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.75	IC50	18	nM	CHEMBL4866400
6.44	IC50	366	nM	CHEMBL4866400
6.10	Ki	800	nM	CHEMBL4848172
5.70	Ki	2000	nM	CHEMBL4865548
5.44	Ki	3600	nM	CHEMBL4861323
5.27	Ki	5400	nM	CHEMBL4878103

PubChem BioAssay actives

6 with measured affinity, of 95 total; 5 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
1-[(E,2S,3R)-1,3-dihydroxyoctadec-4-en-2-yl]-3-hexylurea	1757370: Inhibition of recombinant human ASAH2 using RBM14C24 fluorogenic substrate measured at pH 7.5	ic50	0.0180	uM
4-heptyl-N-[(E,2R,3R)-3-hydroxyheptadec-4-en-2-yl]benzamide	1757356: Non-competitive inhibition of recombinant ASAH2 stably over expressed in human A-375 cell lysate using RBM14C24 as substrate	ki	0.8000	uM
N-[(E,2R,3R)-3-hydroxyheptadec-4-en-2-yl]octanamide	1757356: Non-competitive inhibition of recombinant ASAH2 stably over expressed in human A-375 cell lysate using RBM14C24 as substrate	ki	2.0000	uM
N-[(E,2R,3R)-3-hydroxyheptadec-4-en-2-yl]-4-[3-(methoxymethoxy)propoxy]benzamide	1757356: Non-competitive inhibition of recombinant ASAH2 stably over expressed in human A-375 cell lysate using RBM14C24 as substrate	ki	3.6000	uM
N-[(E,2R,3R)-3-hydroxyheptadec-4-en-2-yl]-4-[4-(methoxymethoxy)butoxy]benzamide	1757356: Non-competitive inhibition of recombinant ASAH2 stably over expressed in human A-375 cell lysate using RBM14C24 as substrate	ki	5.4000	uM

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
N,N-dimethylsphingosine	decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1
N-palmitoylsphingosine	increases abundance, decreases reaction	1
Arsenic Trioxide	increases expression	1
Leflunomide	increases expression	1
Allergens	affects cotreatment, decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Vehicle Emissions	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Doxorubicin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Sodium Selenite	increases expression	1
Particulate Matter	affects cotreatment, decreases expression, increases abundance	1

ChEMBL screening assays

24 unique, capped per target: 24 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2026161	Binding	Inhibition of nCDase in Moh.pAS cells using CerC12NBD as substrate after 1 hr by HPLC-FD analysis	3-Deoxy-3,4-dehydro analogs of XM462. Preparation and activity on sphingolipid metabolism and cell fate. — Bioorg Med Chem

Clinical trials (associated diseases)

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