SMPD2

Summary

SMPD2 (sphingomyelin phosphodiesterase 2, HGNC:11121) is a protein-coding gene on chromosome 6q21, encoding Sphingomyelin phosphodiesterase 2 (O60906). Catalyzes, at least in vitro, the hydrolysis of sphingomyelin to form ceramide and phosphocholine.

This gene encodes a protein which was initially identified as a sphingomyelinase based on sequence similarity between bacterial sphingomyelinases and a yeast protein. Subsequent studies showed that its biological function is less likely to be as a sphingomyelinase and instead as a lysophospholipase.

Source: NCBI Gene 6610 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 68 total
• Druggable target: yes
• MANE Select transcript: NM_003080

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11121
Approved symbol	SMPD2
Name	sphingomyelin phosphodiesterase 2
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	nSMase, ISC1
Ensembl gene	ENSG00000135587
Ensembl biotype	protein_coding
OMIM	603498
Entrez	6610

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000258052, ENST00000439615, ENST00000458487, ENST00000882801, ENST00000882802

RefSeq mRNA: 1 — MANE Select: NM_003080 NM_003080

CCDS: CCDS5075

Canonical transcript exons

ENST00000258052 — 10 exons

Exon	Start	End
ENSE00000918984	109440724	109441171
ENSE00000918985	109441357	109441453
ENSE00000918986	109441552	109441628
ENSE00000918988	109442210	109442299
ENSE00000918989	109442543	109442625
ENSE00000918990	109442752	109442884
ENSE00000918991	109442977	109443081
ENSE00000918992	109443267	109443420
ENSE00000918993	109443517	109443919
ENSE00003559923	109441974	109442067

Expression profiles

Bgee: expression breadth ubiquitous, 200 present calls, max score 93.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.5276 / max 371.8702, expressed in 1810 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
69238	8.8332	1755
69239	5.4176	1698
69240	0.8959	522
69241	0.2319	73
69237	0.1025	33
69236	0.0466	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	93.77	gold quality
left testis	UBERON:0004533	93.52	gold quality
right testis	UBERON:0004534	93.47	gold quality
lower esophagus mucosa	UBERON:0035834	90.76	gold quality
testis	UBERON:0000473	90.05	gold quality
mucosa of transverse colon	UBERON:0004991	89.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.76	gold quality
esophagus mucosa	UBERON:0002469	87.72	gold quality
sperm	CL:0000019	87.01	gold quality
gingival epithelium	UBERON:0001949	86.80	gold quality
bronchial epithelial cell	CL:0002328	86.08	gold quality
granulocyte	CL:0000094	85.99	gold quality
skin of abdomen	UBERON:0001416	85.90	gold quality
right lobe of thyroid gland	UBERON:0001119	85.74	gold quality
body of pancreas	UBERON:0001150	85.63	gold quality
gingiva	UBERON:0001828	85.60	gold quality
skin of leg	UBERON:0001511	85.48	gold quality
left lobe of thyroid gland	UBERON:0001120	85.05	gold quality
epithelium of bronchus	UBERON:0002031	84.96	gold quality
minor salivary gland	UBERON:0001830	84.95	gold quality
male germ cell	CL:0000015	84.53	gold quality
mouth mucosa	UBERON:0003729	84.33	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.07	gold quality
ectocervix	UBERON:0012249	84.04	gold quality
bronchus	UBERON:0002185	84.02	gold quality
body of stomach	UBERON:0001161	83.97	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.93	gold quality
adenohypophysis	UBERON:0002196	83.64	gold quality
saliva-secreting gland	UBERON:0001044	83.61	gold quality
transverse colon	UBERON:0001157	83.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.22

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 18)

• nSMase2 functions as a growth suppressor in MCF7 cells, linking confluence to the G(0)/G(1) cell cycle check point. (PMID:15051724)
• reduction in SMase-generating ceramides and impaired differentiation are involved in the defective barrier function found in atopic dermatitis (PMID:15175033)
• identification of 15 polymorphisms, including 9 novel SNPs, in the SMPD2 gene; one haplotype showed associations with the extrinsic type of atopic dermatitis subgroup (PMID:17212982)
• The catalytic region of neutral sphingomyelinase 2 where palmitoylation occurs is found to be localized at the inner leaflet of the plasma membrane. (PMID:17272284)
• This study underlines the importance of neutral sphingomyelinase-ceramide pathway in mediating oxidative stress-induced apoptosis and cell death of human primary oligodendrocytes. (PMID:18040843)
• Data show DA remarkably increased the NSMase2 message and protein, whereas little change in NSMase1 and NSMase3 mRNAs. (PMID:19698806)
• inhibition of both A- and N1-Smase might explain the upregulatory effect of agLDL on TF activation, and suggest that this effect is related, at least in part, to membrane SM enrichment. (PMID:19817993)
• N-SMase at the cytofacial plasma membrane is an essential element for the proper orientation of PMNs in FMLP gradients, at least in part by polarizing the distribution of Rac 1/2 and RhoA GTPases. (PMID:20378749)
• nSMase2 has a role in ceramide generation, aberrant apoptosis, and lung injury under cigarette smoke exposure (PMID:20448054)
• Results demonstrate that WithaD enhance the ceramide accumulation by activating N-SMase 2, modulate phosphorylation of the JNK and p38MAPK and induced apoptosis in both myeloid and lymphoid cells along with primary cells derived from leukemia patients. (PMID:20836852)
• 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)
• NSM2 plays a key role in the cellular response to hyperosmolar stress, and its activity regulates both cytokine secretion and lipid droplet formation. (PMID:22899568)
• These data suggest that Ox-LDL activates N-SMase-ceramide signaling pathway, and stimulates phosphorylation of p38 MAPK, leading to apoptosis in vascular smooth muscle cells, which initiates VSMC calcification. (PMID:24358176)
• nSMase1 (sphingomyelin phosphodiesterase 2, SMPD2)has a common central role in ceramide signaling during the stress and cytokine responses and apoptosis. (PMID:25168245)
• Interestingly, neutral but not acid sphingomyelinase was mandatory for PorBIA -mediated Neisseria gonorrhoeae invasion into host cells. (PMID:25224994)
• Low NSMase1 expression is associated with hepatocellular carcinoma. (PMID:30106227)
• Genome-wide methylation association with current suicidal ideation in schizophrenia. (PMID:32661777)
• Neutral sphingomyelinase inhibition promotes local and network degeneration in vitro and in vivo. (PMID:37904133)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	smpd2a	ENSDARG00000040523
danio_rerio	smpd2b	ENSDARG00000052701
mus_musculus	Smpd2	ENSMUSG00000019822
rattus_norvegicus	Smpd2	ENSRNOG00000000306
drosophila_melanogaster	nSMase	FBGN0035421
caenorhabditis_elegans	T27F6.6	WBGENE00012105

Protein

Protein identifiers

Sphingomyelin phosphodiesterase 2 — O60906 (reviewed: O60906)

Alternative names: Lyso-platelet-activating factor-phospholipase C, Neutral sphingomyelinase

All UniProt accessions (2): O60906, H0Y5N2

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes, at least in vitro, the hydrolysis of sphingomyelin to form ceramide and phosphocholine. Also hydrolyzes 1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine (lyso-platelet-activating factor) in vivo. Also acts on 1-acyl-2-lyso-sn-glycero-3-phosphocholine (lyso-PC) and sphingosylphosphocholine.

Subcellular location. Cell membrane.

Pathway. Lipid metabolism; sphingolipid metabolism.

Similarity. Belongs to the neutral sphingomyelinase family.

RefSeq proteins (1): NP_003071* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005135	Endo/exonuclease/phosphatase	Domain
IPR036691	Endo/exonu/phosph_ase_sf	Homologous_superfamily
IPR038772	Sph/SMPD2-like	Family

Pfam: PF03372

Enzyme classification (BRENDA):

• EC 3.1.4.12 — sphingomyelin phosphodiesterase (BRENDA: 30 organisms, 220 substrates, 319 inhibitors, 54 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
SPHINGOMYELIN	0.0006–13	30
2-N-HEXADECANOYLAMINO-4-NITROPHENYLPHOSPHORYLCHO	0.034–0.34	2
4-(4-NITROPHENOXY)-2-HYDROXY-BUTYL-1-PHOSPHORYLC	12.6–39.6	2
1-ALKYL-LYSO-PLATELET ACTIVATING FACTOR	0.048	1
2-(N-HEXADECANOYLAMINO)-4-NITROPHENYLPHOSPHORYLC	1.7	1
2N-HEXADECANOYLAMINO-4-NITROPHENYLPHOSPHORYLCHOL	0.027	1
4-NITROPHENYL PHOSPHORYLCHOLINE	11.6	1
ADP	0.306	1
ADP-RIBOSE	0.348	1
ATP	0.327	1
BIS-P-NITROPHENYL PHOSPHATE	14.5	1
BODIPYFL-C12-SPHINGOMYELIN	0.06	1
CDP-CHOLINE	0.262	1
CDP-ETHANOLAMINE	0.391	1
HEXADECANOYL-P-NITROPHENYL PHOSPHORYLCHOLINE	0.174	1

Catalyzed reactions (Rhea), 6 shown:

• a sphingomyelin + H2O = phosphocholine + an N-acylsphing-4-enine + H(+) (RHEA:19253)
• 1-O-hexadecyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycerol + phosphocholine + H(+) (RHEA:36087)
• 1-O-octadecyl-sn-glycero-3-phosphocholine + H2O = 1-O-octadecyl-sn-glycerol + phosphocholine + H(+) (RHEA:39923)
• 1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycerol + phosphocholine + H(+) (RHEA:41119)
• a sphingosylphosphocholine + H2O = a sphingoid base + phosphocholine + H(+) (RHEA:45296)
• an N-(acyl)-sphingosylphosphocholine + H2O = an N-acyl-sphingoid base + phosphocholine + H(+) (RHEA:45300)

UniProt features (41 total): strand 16, helix 9, turn 6, sequence variant 3, transmembrane region 2, chain 1, region of interest 1, active site 1, binding site 1, site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8J2F	ELECTRON MICROSCOPY	3.07

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60906-F1	90.22	0.81

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): 272 (proton acceptor); 180 (important for substrate recognition)

Ligand- & substrate-binding residues (1): 49

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-193681	Ceramide signalling
R-HSA-5626978	TNFR1-mediated ceramide production
R-HSA-9840310	Glycosphingolipid catabolism

MSigDB gene sets: 157 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BIOCARTA_EDG1_PATHWAY, GOBP_SPHINGOMYELIN_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MEMBRANE_LIPID_CATABOLIC_PROCESS, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, PID_TNF_PATHWAY, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, LIAO_METASTASIS, GOBP_ORGANOPHOSPHATE_CATABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, SANSOM_APC_TARGETS_DN

GO Biological Process (9): sphingomyelin metabolic process (GO:0006684), sphingomyelin catabolic process (GO:0006685), response to mechanical stimulus (GO:0009612), sphingolipid catabolic process (GO:0030149), intracellular signal transduction (GO:0035556), ceramide biosynthetic process (GO:0046513), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665), ceramide metabolic process (GO:0006672)

GO Molecular Function (6): sphingomyelin phosphodiesterase activity (GO:0004767), phosphoric diester hydrolase activity (GO:0008081), metal ion binding (GO:0046872), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), plasma membrane (GO:0005886), caveola (GO:0005901), cell periphery (GO:0071944), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
p75 NTR receptor-mediated signalling	1
TNF signaling	1
Glycosphingolipid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
sphingolipid metabolic process	3
cellular anatomical structure	2
phospholipid metabolic process	1
sphingomyelin metabolic process	1
phospholipid catabolic process	1
sphingolipid catabolic process	1
response to external stimulus	1
response to abiotic stimulus	1
lipid catabolic process	1
intracellular anatomical structure	1
signal transduction	1
ceramide metabolic process	1
sphingolipid biosynthetic process	1
primary metabolic process	1
lipid metabolic process	1
phosphoric diester hydrolase activity	1
sphingophospholipase activity	1
phosphoric ester hydrolase activity	1
cation binding	1
molecular_function	1
binding	1
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
plasma membrane raft	1

Protein interactions and networks

STRING

1048 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMPD2	SMPD3	Q9NY59	983
SMPD2	SMPD4	Q9NXE4	948
SMPD2	SMPD1	P17405	947
SMPD2	NSMAF	Q92636	917
SMPD2	SPTLC1	O15269	811
SMPD2	SPTLC2	O15270	787
SMPD2	SPTLC3	Q9NUV7	787
SMPD2	ASAH2	Q9NR71	747
SMPD2	UGCG	Q16739	744
SMPD2	ASAH1	Q13510	713
SMPD2	SPHK1	Q9NYA1	703
SMPD2	CERS6	Q6ZMG9	701
SMPD2	SPHK2	Q9NRA0	689
SMPD2	CERS2	Q96G23	683
SMPD2	ACER2	Q5QJU3	674

IntAct

139 interactions, top by confidence:

A	B	Type	Score
STK24	STRN	psi-mi:“MI:0914”(association)	0.870
PRKAG2	PRKAB2	psi-mi:“MI:0914”(association)	0.730
LRRC32	SMPD2	psi-mi:“MI:0914”(association)	0.640
SMPD2	MTHFR	psi-mi:“MI:0914”(association)	0.560
SMPD2	ARFIP1	psi-mi:“MI:0915”(physical association)	0.560
SMPD2	PITPNC1	psi-mi:“MI:0915”(physical association)	0.560
SMPD2	GAD2	psi-mi:“MI:0915”(physical association)	0.560
SMPD2	PBX3	psi-mi:“MI:0915”(physical association)	0.560
SMPD2	NDRG4	psi-mi:“MI:0915”(physical association)	0.560
SMPD2	COQ8A	psi-mi:“MI:0915”(physical association)	0.560
	SMPD2	psi-mi:“MI:0915”(physical association)	0.560
CCN1	SMPD2	psi-mi:“MI:0915”(physical association)	0.560
SMPD2	STAR	psi-mi:“MI:0915”(physical association)	0.560
SMPD2	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
SMPD2	SLC10A1	psi-mi:“MI:0915”(physical association)	0.560
PGRMC2	SMPD2	psi-mi:“MI:0915”(physical association)	0.560
SMPD2	SLC7A8	psi-mi:“MI:0915”(physical association)	0.560
SMPD2	TMEM167B	psi-mi:“MI:0915”(physical association)	0.560
SMPD2	SH3GLB1	psi-mi:“MI:0915”(physical association)	0.560
SMPD2	MTHFR	psi-mi:“MI:0915”(physical association)	0.560
FNTB	BLTP3B	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
PCDHB16	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
PCDHB7	C2CD2L	psi-mi:“MI:0914”(association)	0.530
RPN2	SMPD2	psi-mi:“MI:0914”(association)	0.530
PLVAP	SMPD2	psi-mi:“MI:0914”(association)	0.530

BioGRID (125): SMPD2 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), MTHFR (Affinity Capture-MS), ANAPC10 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), SMPD2 (Affinity Capture-MS)

ESM2 similar proteins: A1L1C2, A3KNW0, A6H603, A6NFQ2, A6QLU7, A9ULG4, B1H1N7, E1BE10, E2RD63, O35405, O55230, O60294, O60906, O75771, O95479, P21709, P51839, P56201, Q0V8L6, Q149M9, Q1JPJ9, Q28DT3, Q2KJJ8, Q2TBP8, Q4R583, Q5FVH2, Q5R4Y7, Q5XIA3, Q60750, Q643R3, Q6NVG1, Q6QHF9, Q80XS7, Q865R1, Q8BG07, Q8BYR1, Q8C0L6, Q8CFX1, Q8IV08, Q8N0W3

Diamond homologs: O45870, O60906, O70572, O74369, P40015, Q9ET64, Q9VZS6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1252 predictions. Top by Δscore:

Variant	Effect	Δscore
6:109441168:GCTG:G	donor_gain	1.0000
6:109441172:G:GG	donor_gain	1.0000
6:109441173:T:A	donor_loss	1.0000
6:109441355:AGG:A	acceptor_gain	1.0000
6:109441356:GGG:G	acceptor_gain	1.0000
6:109441356:GGGGC:G	acceptor_gain	1.0000
6:109441451:G:GT	donor_gain	1.0000
6:109442205:TGCA:T	acceptor_loss	1.0000
6:109442206:GCAGA:G	acceptor_loss	1.0000
6:109442207:CA:C	acceptor_loss	1.0000
6:109442208:A:AC	acceptor_loss	1.0000
6:109442209:G:GT	acceptor_loss	1.0000
6:109442300:G:GG	donor_gain	1.0000
6:109442541:A:AG	acceptor_gain	1.0000
6:109442542:G:GG	acceptor_gain	1.0000
6:109442542:GCTCC:G	acceptor_gain	1.0000
6:109442626:GTGT:G	donor_gain	1.0000
6:109442628:GT:G	donor_gain	1.0000
6:109442630:G:GG	donor_gain	1.0000
6:109442651:G:GT	donor_gain	1.0000
6:109442651:G:T	donor_gain	1.0000
6:109442736:AACCT:A	acceptor_gain	1.0000
6:109442740:T:TA	acceptor_gain	1.0000
6:109442750:A:AG	acceptor_gain	1.0000
6:109442751:G:GA	acceptor_gain	1.0000
6:109442751:GC:G	acceptor_gain	1.0000
6:109442751:GCC:G	acceptor_gain	1.0000
6:109442751:GCCA:G	acceptor_gain	1.0000
6:109442751:GCCAC:G	acceptor_gain	1.0000
6:109442882:AAGG:A	donor_loss	1.0000

AlphaMissense

2766 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:109442288:T:G	Y133D	0.987
6:109442588:C:A	R152S	0.983
6:109442800:C:A	N180K	0.982
6:109442800:C:G	N180K	0.982
6:109442003:T:C	F85S	0.981
6:109442589:G:C	R152P	0.981
6:109442600:G:C	A156P	0.980
6:109442793:A:T	D178V	0.980
6:109442794:C:A	D178E	0.980
6:109442794:C:G	D178E	0.980
6:109442796:T:C	L179P	0.979
6:109443058:C:A	R236S	0.979
6:109441162:T:C	L14P	0.978
6:109441437:T:C	L44P	0.978
6:109442000:T:A	V84D	0.978
6:109442786:T:C	C176R	0.976
6:109442850:T:C	L197P	0.976
6:109441452:A:T	E49V	0.974
6:109442790:G:A	G177E	0.974
6:109441622:T:C	F73S	0.973
6:109442250:T:C	L120P	0.973
6:109442793:A:C	D178A	0.973
6:109441580:T:C	L59P	0.972
6:109441391:C:A	R29S	0.971
6:109441392:G:C	R29P	0.971
6:109441621:T:C	F73L	0.971
6:109441623:C:A	F73L	0.971
6:109441623:C:G	F73L	0.971
6:109442781:T:G	L174R	0.970
6:109441996:T:C	C83R	0.969

dbSNP variants (sampled 300 via entrez): RS1000982062 (6:109440564 G>A,C,T), RS1000992004 (6:109440354 C>G), RS1001982428 (6:109441218 A>G), RS1002211252 (6:109440120 GA>G,GAA), RS1003207558 (6:109438994 C>G), RS1003217914 (6:109438883 G>A), RS1003517837 (6:109443179 G>A), RS1004514456 (6:109439501 G>A), RS1004659456 (6:109440053 G>C), RS1005558765 (6:109439443 G>A,C), RS1007259932 (6:109442398 G>A,T), RS1008456203 (6:109440570 G>C,T), RS1008686392 (6:109439363 T>C), RS1008740615 (6:109439007 G>A,C), RS1010750874 (6:109441699 C>A,G,T)

Disease associations

OMIM: gene MIM:603498 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000175_27	Height	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4712 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Sphingomyelin phosphodiesterase

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
inhibitor A [PMID: 12482429]	Inhibition	5.8	pKi

ChEMBL bioactivities

8 potent at pChembl≥5 of 9 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.52	IC50	300	nM	CHEMBL5284450
6.00	IC50	1000	nM	CHEMBL5278618
6.00	IC50	1000	nM	SCYPHOSTATIN
6.00	IC50	1000	nM	CHEMBL310981
5.80	Ki	1600	nM	CHEMBL310981
5.75	IC50	1800	nM	CHEMBL5284579
5.55	IC50	2800	nM	CHEMBL5270975
5.48	IC50	3300	nM	CHEMBL310981

PubChem BioAssay actives

8 with measured affinity, of 40 total; 6 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
phenyl N-[(3R)-1-[7-(3,4-dimethoxyphenyl)-2,6-dimethylpyrrolo[1,2-b]pyridazin-4-yl]pyrrolidin-3-yl]carbamate	1923529: Inhibition of human recombinant nSMase	ic50	0.3000	uM
(2E,4E,6E,8R,10S,12E,14R)-N-[(2S)-1-hydroxy-3-[(1S,2S,6S)-2-hydroxy-3-oxo-7-oxabicyclo[4.1.0]hept-4-en-2-yl]propan-2-yl]-8,10,12,14-tetramethylhexadeca-2,4,6,12-tetraenamide	147530: Inhibitory activity against neutral sphingomyelinase (N-SMase) from bovine brain microsomes	ic50	1.0000	uM
N-[(3R)-1-[7-(3,4-dimethoxyphenyl)-2,6-dimethylpyrrolo[1,2-b]pyridazin-4-yl]pyrrolidin-3-yl]acetamide	1923529: Inhibition of human recombinant nSMase	ic50	1.0000	uM
[(3S,4R)-1,1-difluoro-3-(hexadecanoylamino)-4-hydroxy-4-phenylbutyl]phosphonic acid	147531: Inhibitory activity against schyphostatin of neutral sphingomyelinase (N-SMase) from bovine brain microsome	ic50	1.0000	uM
(2S)-2-[bis[(E)-3-naphthalen-1-ylprop-2-enyl]amino]-3-hydroxypropanoic acid	1923523: Inhibition of nSMase in human U-937 cells	ic50	1.8000	uM
(2S)-2-[bis[(E)-3-naphthalen-1-ylprop-2-enyl]amino]propanoic acid	1923523: Inhibition of nSMase in human U-937 cells	ic50	2.8000	uM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
sphingosine 1-phosphate	decreases reaction, increases activity	1
perfluorooctane sulfonic acid	decreases expression	1
27-hydroxycholesterol	decreases activity	1
perfluoro-n-nonanoic acid	decreases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Carmustine	increases expression	1
Ceramides	increases abundance	1
Cisplatin	increases expression, affects cotreatment	1
NAD	affects activity	1
Dihydrotestosterone	increases expression	1
Thalidomide	decreases reaction, increases activity	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

ChEMBL screening assays

13 unique, capped per target: 13 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4153027	Binding	Inhibition of neutral sphingomyelinase (unknown origin) assessed as reduction in NBD-ceramide release at 100 uM by TLC based fluorescence assay	Discovery of N-hydroxy-3-alkoxybenzamides as direct acid sphingomyelinase inhibitors using a ligand-based pharmacophore model. — Eur J Med Chem

Clinical trials (associated diseases)

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