SGMS1

Summary

SGMS1 (sphingomyelin synthase 1, HGNC:29799) is a protein-coding gene on chromosome 10q11.23, encoding Phosphatidylcholine:ceramide cholinephosphotransferase 1 (Q86VZ5). Major sphingomyelin synthase at the Golgi apparatus.

The protein encoded by this gene is predicted to be a five-pass transmembrane protein. This gene may be predominately expressed in brain.

Source: NCBI Gene 259230 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Moderate, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 35 total — 2 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_147156

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29799
Approved symbol	SGMS1
Name	sphingomyelin synthase 1
Location	10q11.23
Locus type	gene with protein product
Status	Approved
Aliases	MOB, MGC17342, SMS1
Ensembl gene	ENSG00000198964
Ensembl biotype	protein_coding
OMIM	611573
Entrez	259230

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 42 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000361543, ENST00000361781, ENST00000429490, ENST00000492601, ENST00000498514, ENST00000602565, ENST00000602619, ENST00000608287, ENST00000609445, ENST00000619438, ENST00000626236, ENST00000892763, ENST00000892764, ENST00000892765, ENST00000892766, ENST00000892767, ENST00000892768, ENST00000892769, ENST00000892770, ENST00000892771, ENST00000892772, ENST00000892773, ENST00000892774, ENST00000892775, ENST00000892776, ENST00000892777, ENST00000892778, ENST00000892779, ENST00000892780, ENST00000892781, ENST00000892782, ENST00000892783, ENST00000892784, ENST00000892785, ENST00000892786, ENST00000892787, ENST00000892788, ENST00000922989, ENST00000922990, ENST00000922991, ENST00000922992, ENST00000922993, ENST00000963914, ENST00000963915, ENST00000963916, ENST00000963917, ENST00000963918

RefSeq mRNA: 1 — MANE Select: NM_147156 NM_147156

CCDS: CCDS7240

Canonical transcript exons

ENST00000361781 — 11 exons

Exon	Start	End
ENSE00001124740	50343492	50344345
ENSE00001231654	50433476	50433556
ENSE00001231663	50460673	50460814
ENSE00001339695	50466890	50466932
ENSE00001339697	50519831	50519921
ENSE00001339701	50590153	50590247
ENSE00001823209	50623707	50623956
ENSE00001891402	50305600	50307321
ENSE00003578660	50327205	50327322
ENSE00003716264	50311262	50311415
ENSE00003729490	50307982	50308148

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 96.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.0354 / max 325.6449, expressed in 1814 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109361	15.5793	1789
109352	9.5324	1401
109353	2.8701	991
109360	0.7593	344
109362	0.7447	444
109363	0.6597	296
109359	0.6000	293
205866	0.5727	319
109364	0.5447	261
109365	0.1726	68

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	96.84	gold quality
calcaneal tendon	UBERON:0003701	95.55	gold quality
palpebral conjunctiva	UBERON:0001812	95.50	gold quality
pigmented layer of retina	UBERON:0001782	94.70	gold quality
choroid plexus epithelium	UBERON:0003911	92.85	gold quality
germinal epithelium of ovary	UBERON:0001304	92.44	gold quality
corpus callosum	UBERON:0002336	91.46	gold quality
hair follicle	UBERON:0002073	91.24	gold quality
upper leg skin	UBERON:0004262	90.73	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.44	gold quality
skin of hip	UBERON:0001554	90.28	gold quality
sural nerve	UBERON:0015488	90.09	gold quality
spinal cord	UBERON:0002240	89.61	gold quality
penis	UBERON:0000989	89.10	gold quality
visceral pleura	UBERON:0002401	89.07	gold quality
lower lobe of lung	UBERON:0008949	88.87	gold quality
colonic epithelium	UBERON:0000397	88.55	gold quality
skin of abdomen	UBERON:0001416	88.49	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.23	gold quality
epithelium of nasopharynx	UBERON:0001951	88.02	gold quality
jejunal mucosa	UBERON:0000399	87.98	gold quality
zone of skin	UBERON:0000014	87.77	gold quality
corpus epididymis	UBERON:0004359	87.64	gold quality
monocyte	CL:0000576	87.56	gold quality
lung	UBERON:0002048	87.43	gold quality
synovial joint	UBERON:0002217	87.43	gold quality
pleura	UBERON:0000977	87.38	gold quality
mononuclear cell	CL:0000842	87.33	gold quality
gall bladder	UBERON:0002110	87.22	gold quality
parietal pleura	UBERON:0002400	87.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

209 targeting SGMS1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548N	99.98	71.94	4170
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-507	99.97	70.11	1915
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-1250-3P	99.96	70.04	4038

Literature-anchored findings (GeneRIF, showing 40)

• The 1.6 kb Hmob33 clone obtained from the medulla oblongata cDNA library and mapped to the human chromosome 10 was examined to find the coding region(MOB) (PMID:11841947)
• SMS1 is responsible for SM synthase activity in mammalian cells and plays a critical role in cell growth of lymphoid cells. (PMID:14976195)
• MOB gene activity is believed to be controlled at least at the transcriptional and the posttranscriptional levels, strictly regulating the amount of the encoded protein product. (PMID:15315829)
• Adenovirus-mediated SMS1 overexpression increased lipoprotein atherogenic potential. (PMID:16508036)
• Data show that sphingomyelin synthases SMS1 and SMS2 are co-expressed in a variety of cell types and function as the key Golgi- and plasma membrane-associated SM synthases in human cervical carcinoma HeLa cells, respectively. (PMID:17449912)
• Overexpression of SMS1 is associated with suppressed ceramide response and apoptotic resistance after photodamage. (PMID:17467659)
• Results indicate that both synthase (SMS)1 and 2 contribute to sphingomyelin (SM) de novo synthesis and control SM levels in the cells and on the cell membrane including plasma membrane. (PMID:17616479)
• SMS1 and SMS2 are key factors in the control of sphingomyelin and diacylglycerol metabolism within the cell, and thus they influence apoptosis. (PMID:17982138)
• SMS1 regulates subcellular pools of diacylglycerol-binding proteins in the Golgi apparatus. (PMID:18370930)
• Both SMS1 and SMS2 contain two histidines and one aspartic acid which are conserved within the lipid phosphate phosphatase superfamily. Site-directed mutagenesis of these amino acids abolished SMS activity without altering cellular distribution. (PMID:18694848)
• Impaired TCR signaling through dysfunction of lipid rafts in SMS1-knockdown T cells (PMID:18820264)
• Results establish the sphingomyelin synthase (SMS1)-related enzyme SMSr as a key regulator of ceramide homeostasis that seems to operate as a sensor rather than a converter of ceramides in the endoplasmic reticulum. (PMID:19506037)
• Altogether, our data show that SMS1 is a novel caspase target that is functionally involved in the regulation of FasL-induced apoptosis. (PMID:19779494)
• sphingomyelin synthase has a role in controlling the antimicrobial activity of neutrophils against Cryptococcus neoformans (PMID:21203393)
• Cellular sphingomyelin levels are positively related to cellular cholesterol levels and sphingomyelin synthase overexpression-mediated cellular sphingomyelin content changes are related to cellular Apo A-I content and secretion (PMID:21418611)
• Our results indicate that the regulation of SMS1 expression is complex and occurs at the transcriptional, post-transcriptional and translational levels. (PMID:21549185)
• SMS1-mediated SM synthesis directs Tf-TfR to undergo clathrin-dependent endocytosis and recycling, promoting the proliferation of lymphoma cells. (PMID:21856749)
• SMS1 and SMS2 are capable of regulating TGN-mediated protein trafficking and secretion (PMID:21980337)
• Data indicate that the increased sphingomyelin mass was due to a rapid and highly specific activation of sphingomyelin synthases SMS1 and SMS2. (PMID:22106271)
• Findings indicate that Sms1 is a downstream target of Bcr-abl, involved in sustaining cell proliferation of Bcr-abl-positive cells. (PMID:23160178)
• SGMS activity impacts on amyloid precursor protein processing to produce amyloid-beta (Abeta) and it could be a contributing factor in Abeta pathology associated with Alzheimer’s disease. (PMID:23977395)
• The amount of SMS1 transcripts varies considerably between different human tissues. (PMID:24062078)
• We found upregulation of specific sphingolipid enzymes, namely sphingomyelin synthase 1 (SMS1), sphingomyelinase 3 (SMPD3), and glucosylceramide synthase (GCS) in the endometrium of endometriotic women. (PMID:24960545)
• A study of the expression of the full-length SMS1 protein and the sum of the alternative transcripts encoding this protein in human tissues. (PMID:25912551)
• The structural organization of 5’-UTR variants of SGMS1 transcripts, directed by alternative promoters, is substantially different; this can provide regulation of the gene functioning on post-transcriptional level. (PMID:26065260)
• Sphingomyelin synthase 1 positively regulates KCNQ1/KCNE1 channel density in a protein kinase D-dependent manner. (PMID:27194473)
• SMS regulates the expression and function of drug transporters P-gp and MRP2. (PMID:27394416)
• findings suggest that the C-terminal tails of SMSs are involved in homodimer formation, which is required for efficient transport from the ER. (PMID:27927984)
• HepG2 cells stably transfected with SMS1 (HepG2-SMS1) exhibit elevated enzyme activity in vitro and increased sphingomyelin content (mainly C22:0- and C24:0-sphingomyelin) but lower hexosylceramide (Hex-Cer) levels. (PMID:28087695)
• The inhibition of SMS 1 activity induced CD cells to lose their epithelial phenotype and to undergo an epithelial-mesenchymal transition (EMT) process. (PMID:29128370)
• the SGMS1 gene exhibits a complex regulation at the post-transcriptional level (PMID:29454087)
• An oncogene-Bcr-Abl-has been demonstrated to drive such a mechanism that up-regulates the expression of a functionally important target gene, SMS1. (PMID:29533737)
• PECULIARITIES OF THE STRUCTURE AND EXPRESSION OF HUMAN SPHINGOMYELIN SYNTHASE 1 GENE (SGMS1). (PMID:30191692)
• findings suggest that complex formation between SMS1 and GCS is part of a critical mechanism controlling the metabolic fate of Cer in the Golgi. (PMID:30242129)
• SMS1 could inhibit EMT and the migration and invasion of MDAMB231 cells via TGFbeta/Smad signaling pathway. (PMID:30535436)
• Differential lung tissue gene expression in males and females: implications for the susceptibility to develop COPD. (PMID:31164434)
• optively transferred wide-type B cells partially recovered B-cell activation and autoantibody production in SMS1 deficient bm12-induced lupus mice. Moreover, the SMS1 mRNA level in B cells of SLE patients was increased and positively correlated with the serum anti-dsDNA level, IgG and globulin titers. (PMID:31262710)
• Chlamydia trachomatis-infected human cells convert ceramide to sphingomyelin without sphingomyelin synthases 1 and 2. (PMID:31596951)
• Diacylglycerol kinase delta and sphingomyelin synthase-related protein functionally interact via their sterile alpha motif domains. (PMID:31980461)
• Regulation of human sphingomyelin synthase 1 translation through its 5’-untranslated region. (PMID:33037626)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sgms1b	ENSDARG00000029621
danio_rerio	sgms1a	ENSDARG00000057053
mus_musculus	Sgms1	ENSMUSG00000040451
rattus_norvegicus	Sgms1	ENSRNOG00000012536
caenorhabditis_elegans		WBGENE00004892

Paralogs (2): SAMD8 (ENSG00000156671), SGMS2 (ENSG00000164023)

Protein

Protein identifiers

Phosphatidylcholine:ceramide cholinephosphotransferase 1 — Q86VZ5 (reviewed: Q86VZ5)

Alternative names: Medulla oblongata-derived protein, Sphingomyelin synthase 1, Transmembrane protein 23

All UniProt accessions (5): Q86VZ5, C0MHM2, E6ZCI6, R4GNI5, U3KQ11

UniProt curated annotations — full annotation on UniProt →

Function. Major sphingomyelin synthase at the Golgi apparatus. Catalyzes the reversible transfer of phosphocholine moiety in sphingomyelin biosynthesis: in the forward reaction transfers phosphocholine head group of phosphatidylcholine (PC) on to ceramide (CER) to form ceramide phosphocholine (sphingomyelin, SM) and diacylglycerol (DAG) as by-product, and in the reverse reaction transfers phosphocholine from SM to DAG to form PC and CER. The direction of the reaction depends on the levels of CER and DAG in Golgi membranes. Converts the newly synthesized CER, that is transported from the endoplasmic reticulum to the trans-Golgi by the Cer transport protein (CERT), to SM. Can form a heteromeric complex with glucosylceramide synthase (GCS) increasing SMS activity and reducing glucosylceramide synthesis, a critical mechanism that controls the metabolic fate of CER in the Golgi. Does not use free phosphorylcholine or CDP-choline as donor. Can also transfer phosphoethanolamine head group of phosphatidylethanolamine (PE) on to CER to form ceramide phosphoethanolamine (CPE). Regulates receptor-mediated signal transduction via mitogenic DAG and proapoptotic CER, as well as via SM, a structural component of membrane rafts that serve as platforms for signal transduction and protein sorting. Plays a role in secretory transport via regulation of DAG pool at the Golgi apparatus and its downstream effects on PRKD1.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Widely expressed.

Activity regulation. Inhibited by bacterial PC-phospholipase C inhibitor D609.

Pathway. Sphingolipid metabolism.

Miscellaneous. Overexpression of the human protein in mouse causes increased non-HDL-sphingomyelin and non-HDL cholesterol levels, decreased HDL-sphingomyelin and HDL-cholesterol levels and increases the atherogenic potential of non-HDL lipoprotein particles.

Similarity. Belongs to the sphingomyelin synthase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86VZ5-1	1	yes
Q86VZ5-2	2

RefSeq proteins (1): NP_671512* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR025749	Sphingomyelin_synth-like_dom	Domain
IPR045221	Sphingomyelin_synth-like	Family

Pfam: PF14360

Enzyme classification (BRENDA):

• EC 2.7.8.27 — sphingomyelin synthase (BRENDA: 12 organisms, 39 substrates, 97 inhibitors, 8 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
C6-CERAMIDE	0.0063–0.0072	2
C8-CERAMIDE	0.0054–0.0055	2
6-((N-(7-NITROBENZ-2-OXA-1,3-DIAZOL-4-YL)AMINO)H	0.0075	1
C17-CERAMIDE	0.0003	1
DIACYLGLYCEROL	0.112	1
SPHINGOMYELIN	0.0356	1

Catalyzed reactions (Rhea), 7 shown:

• an N-acylsphing-4-enine + a 1,2-diacyl-sn-glycero-3-phosphocholine = a sphingomyelin + a 1,2-diacyl-sn-glycerol (RHEA:18765)
• an N-acylsphing-4-enine + a 1,2-diacyl-sn-glycero-3-phosphoethanolamine = an N-acylsphing-4-enine 1-phosphoethanolamine + a 1,2-diacyl-sn-glycerol (RHEA:36079)
• N-hexadecanoylsphinganine + a 1,2-diacyl-sn-glycero-3-phosphocholine = N-hexadecanoyl-sphinganine-1-phosphocholine + a 1,2-diacyl-sn-glycerol (RHEA:41796)
• N-hexadecanoyl-(4R)-hydroxysphinganine + a 1,2-diacyl-sn-glycero-3-phosphocholine = N-hexadecanoyl-(4R)-hydroxysphinganine-phosphocholine + a 1,2-diacyl-sn-glycerol (RHEA:42140)
• an N-acyl-(4R)-4-hydroxysphinganine + a 1,2-diacyl-sn-glycero-3-phosphocholine = an N-acyl-(4R)-4-hydroxysphinganine-phosphocholine + a 1,2-diacyl-sn-glycerol (RHEA:42152)
• 1-(9Z-octadecenoyl)-2-acyl-sn-3-glycerol + a sphingomyelin = a 1-(9Z-octadecenoyl)-2-acyl-sn-glycero-3-phosphocholine + an N-acylsphing-4-enine (RHEA:43320)
• an N-acylsphinganine + a 1,2-diacyl-sn-glycero-3-phosphocholine = an N-acylsphinganine-1-phosphocholine + a 1,2-diacyl-sn-glycerol (RHEA:44620)

UniProt features (26 total): topological domain 7, transmembrane region 6, mutagenesis site 4, active site 3, splice variant 2, chain 1, domain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86VZ5-F1	79.55	0.38

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 (3): 285; 328; 332

Post-translational modifications (1): 8

Mutagenesis-validated functional residues (4):

Position	Phenotype
283	completely abolishes enzyme activity. no change in subcellular location.
285	completely abolishes enzyme activity. no change in subcellular location.
328	completely abolishes enzyme activity. no change in subcellular location.
332	completely abolishes enzyme activity. no change in subcellular location.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1660661	Sphingolipid de novo biosynthesis
R-HSA-1430728	Metabolism
R-HSA-428157	Sphingolipid metabolism
R-HSA-556833	Metabolism of lipids

MSigDB gene sets: 364 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_SPHINGOMYELIN_METABOLIC_PROCESS, GOZGIT_ESR1_TARGETS_DN, AAGCCAT_MIR135A_MIR135B, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, TTGGGAG_MIR150, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, GTGCCTT_MIR506, RICKMAN_METASTASIS_DN, MYOD_01, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_SPHINGOLIPID_METABOLIC_PROCESS

GO Biological Process (7): sphingomyelin biosynthetic process (GO:0006686), apoptotic process (GO:0006915), sphingolipid biosynthetic process (GO:0030148), ceramide biosynthetic process (GO:0046513), regulation of intrinsic apoptotic signaling pathway (GO:2001242), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665)

GO Molecular Function (7): ceramide phosphoethanolamine synthase activity (GO:0002950), kinase activity (GO:0016301), sphingomyelin synthase activity (GO:0033188), ceramide cholinephosphotransferase activity (GO:0047493), protein binding (GO:0005515), transferase activity (GO:0016740), phosphotransferase activity, for other substituted phosphate groups (GO:0016780)

GO Cellular Component (8): Golgi trans cisterna (GO:0000138), Golgi membrane (GO:0000139), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), membrane (GO:0016020), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Sphingolipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphotransferase activity, for other substituted phosphate groups	3
intracellular membrane-bounded organelle	3
sphingolipid biosynthetic process	2
transferase activity, transferring phosphorus-containing groups	2
cytoplasm	2
endomembrane system	2
sphingomyelin metabolic process	1
phospholipid biosynthetic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
sphingolipid metabolic process	1
lipid biosynthetic process	1
ceramide metabolic process	1
intrinsic apoptotic signaling pathway	1
regulation of intracellular signal transduction	1
regulation of apoptotic signaling pathway	1
primary metabolic process	1
lipid metabolic process	1
binding	1
catalytic activity	1
Golgi cisterna	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

732 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SGMS1	CERS3	Q8IU89	763
SGMS1	SMPD1	P17405	728
SGMS1	SPTLC1	O15269	695
SGMS1	CERK	Q8TCT0	688
SGMS1	CERS2	Q96G23	656
SGMS1	UGCG	Q16739	650
SGMS1	SMPD4	Q9NXE4	649
SGMS1	SMPD2	O60906	645
SGMS1	SPTLC2	O15270	638
SGMS1	SPTLC3	Q9NUV7	635
SGMS1	CERS6	Q6ZMG9	632
SGMS1	KDSR	Q06136	631
SGMS1	CERS4	Q9HA82	630
SGMS1	ASAH1	Q13510	627
SGMS1	DEGS1	O15121	605

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ATXN1	SGMS1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): SGMS1 (Synthetic Lethality), SGMS1 (Affinity Capture-RNA), SGMS1 (Affinity Capture-RNA), SGMS1 (Affinity Capture-RNA), SGMS1 (Proximity Label-MS), SGMS1 (Proximity Label-MS), SGMS1 (Proximity Label-MS), SGMS1 (Proximity Label-MS), SGMS1 (Proximity Label-MS), SGMS1 (Proximity Label-MS), SGMS1 (Proximity Label-MS), SGMS1 (Proximity Label-MS), SGMS1 (Proximity Label-MS), SGMS1 (Proximity Label-MS), SGMS1 (Proximity Label-MS)

ESM2 similar proteins: A0A078H868, A0AAS4, A0JP80, A6X919, D4AD75, O70536, O77760, O77761, P23913, P35610, P53439, P56079, Q14739, Q20696, Q20735, Q28677, Q2PZI1, Q4JM44, Q4R763, Q5R7H4, Q5RK27, Q60457, Q61263, Q63632, Q63633, Q657W3, Q6AX73, Q6Z0E2, Q7T3T4, Q7TSX5, Q86VZ5, Q8IWX5, Q8NHU3, Q8VCQ6, Q91V14, Q924N4, Q965Q4, Q9D4B1, Q9FJB4, Q9H2X9

Diamond homologs: A0AAS4, Q20696, Q4JM44, Q4R763, Q56Y01, Q7T3T4, Q7TSX5, Q86VZ5, Q8NHU3, Q8VCQ6, Q96LT4, Q9D4B1, Q9DA37, Q9TYV2, Q9U3D4, Q9VS60, Q20735, Q9M325, Q9SH93, B3A0L9, B3A0M1, B3A0M2, B8ACH9, E9AFX2, Q38E53, Q38E55, Q38E56, Q5N7A7, Q965Q4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	24
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
4533203	NM_147156.4(SGMS1):c.677G>A (p.Arg226Gln)	Pathogenic
4533205	NM_147156.4(SGMS1):c.857C>T (p.Thr286Met)	Pathogenic

SpliceAI

4072 predictions. Top by Δscore:

Variant	Effect	Δscore
10:50307974:AAACT:A	donor_loss	1.0000
10:50307975:AACTC:A	donor_loss	1.0000
10:50307976:ACTCA:A	donor_loss	1.0000
10:50307978:TCACT:T	donor_loss	1.0000
10:50307979:C:CC	donor_loss	1.0000
10:50307980:A:AC	donor_gain	1.0000
10:50307980:AC:A	donor_loss	1.0000
10:50307981:C:CA	donor_gain	1.0000
10:50307981:CTTG:C	donor_gain	1.0000
10:50307984:G:A	donor_gain	1.0000
10:50308006:C:CT	donor_gain	1.0000
10:50308007:C:CT	donor_gain	1.0000
10:50308144:GGAAT:G	acceptor_gain	1.0000
10:50308145:GAATC:G	acceptor_loss	1.0000
10:50308146:AATC:A	acceptor_loss	1.0000
10:50308147:AT:A	acceptor_gain	1.0000
10:50308147:ATC:A	acceptor_loss	1.0000
10:50308148:TCT:T	acceptor_loss	1.0000
10:50308149:C:CC	acceptor_gain	1.0000
10:50308150:T:C	acceptor_loss	1.0000
10:50311260:ACACT:A	donor_gain	1.0000
10:50311261:CA:C	donor_gain	1.0000
10:50311261:CACT:C	donor_gain	1.0000
10:50311261:CACTC:C	donor_gain	1.0000
10:50460813:GCCTG:G	acceptor_loss	1.0000
10:50460814:CCTGG:C	acceptor_loss	1.0000
10:50460815:C:CA	acceptor_loss	1.0000
10:50460816:T:C	acceptor_loss	1.0000
10:50466933:C:CC	acceptor_gain	1.0000
10:50590150:TACCT:T	donor_loss	1.0000

AlphaMissense

2735 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:50308049:T:A	D332V	1.000
10:50308060:G:C	H328Q	1.000
10:50308060:G:T	H328Q	1.000
10:50311308:G:C	S283R	1.000
10:50311308:G:T	S283R	1.000
10:50311310:T:G	S283R	1.000
10:50311321:T:A	D279V	1.000
10:50311322:C:G	D279H	1.000
10:50311324:C:T	G278E	1.000
10:50311327:C:G	C277S	1.000
10:50311327:C:T	C277Y	1.000
10:50311328:A:T	C277S	1.000
10:50343552:T:A	E188V	1.000
10:50307276:A:G	W370R	0.999
10:50307276:A:T	W370R	0.999
10:50308037:G:T	A336E	0.999
10:50308048:G:C	D332E	0.999
10:50308048:G:T	D332E	0.999
10:50308049:T:C	D332G	0.999
10:50308049:T:G	D332A	0.999
10:50308050:C:A	D332Y	0.999
10:50308050:C:G	D332H	0.999
10:50308059:A:G	Y329H	0.999
10:50308061:T:A	H328L	0.999
10:50308061:T:G	H328P	0.999
10:50308062:G:A	H328Y	0.999
10:50308062:G:C	H328D	0.999
10:50308091:C:T	G318E	0.999
10:50308092:C:G	G318R	0.999
10:50308092:C:T	G318R	0.999

dbSNP variants (sampled 300 via entrez): RS1000026532 (10:50313763 A>C), RS1000032684 (10:50443743 CT>C), RS1000037569 (10:50488310 C>T), RS1000038487 (10:50398245 G>A), RS1000042954 (10:50360539 C>A), RS1000076963 (10:50403310 T>C), RS1000078090 (10:50323560 T>G), RS1000084282 (10:50590105 G>A,T), RS1000100099 (10:50581167 A>G), RS1000110317 (10:50448612 C>T), RS1000116576 (10:50450716 A>G), RS1000120609 (10:50481290 T>C), RS1000139774 (10:50495341 T>C), RS1000141123 (10:50448850 T>A), RS1000142031 (10:50461821 C>T)

Disease associations

OMIM: gene MIM:611573 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Moderate	Autosomal recessive

Mondo (1): complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001651_46	Response to amphetamines	5.000000e-06
GCST002930_9	Cobalt levels	3.000000e-06
GCST007269_112	Pulse pressure	2.000000e-08
GCST008478_33	Neurological blood protein biomarker levels	6.000000e-12
GCST009698_109	Metabolite levels	1.000000e-08
GCST010243_249	Apolipoprotein B levels	2.000000e-09
GCST010244_148	Triglyceride levels	1.000000e-11
GCST010245_87	LDL cholesterol levels	2.000000e-08
GCST012309_6	Schizophrenia	9.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3611965 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Sphingomyelin synthase

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
compound 1j [PMID: 26314925]	Inhibition	5.68	pIC50
sphingomyelin synthase 2 inhibitor 15w	Inhibition	4.25	pIC50

ChEMBL bioactivities

19 potent at pChembl≥5 of 43 total, top 19 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.07	IC50	850	nM	CHEMBL4641888
6.00	IC50	1000	nM	CHEMBL4172856
5.82	IC50	1500	nM	GINGKOLIC ACID
5.70	IC50	2000	nM	MALABARICONE A
5.70	IC50	2000	nM	MALABARICONE B
5.70	IC50	2000	nM	MALABARICONE C
5.68	IC50	2100	nM	CHEMBL3613983
5.62	IC50	2400	nM	CHEMBL4645607
5.52	IC50	3000	nM	MALABARICONE C
5.47	IC50	3400	nM	CHEMBL4646354
5.46	IC50	3500	nM	MALABARICONE B
5.40	IC50	4000	nM	MALABARICONE A
5.28	IC50	5200	nM	CHEMBL3613975
5.23	IC50	5900	nM	CHEMBL3612087
5.22	IC50	6000	nM	CHEMBL3819036
5.18	IC50	6600	nM	CHEMBL3613987
5.09	IC50	8100	nM	CHEMBL3613984
5.04	IC50	9200	nM	CHEMBL3613995
5.00	IC50	1e+04	nM	CHEMBL4646540

PubChem BioAssay actives

19 with measured affinity, of 150 total; 16 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-methylcyclopropyl) 4-[3-[[3-[[3,5-bis(trifluoromethyl)phenyl]methyl-methylcarbamoyl]-1-methyl-2-oxo-1,8-naphthyridin-4-yl]oxy]propyl]piperidine-1-carboxylate	1667230: Inhibition of human recombinant C-terminal FLAG-tagged SMS1 expressed in mammalian expression system using C14-phosphatidylcholineD72 and C17-ceramide pre-incubated for 60 mins followed by incubation with substrate for 30 mins measured by RapidFire/MS assay	ic50	0.8500	uM
(1-methylcyclopropyl) 4-[3-[3-[[3,5-bis(trifluoromethyl)phenyl]methyl-methylcarbamoyl]-1-methyl-2-oxoquinolin-4-yl]oxypropyl]piperidine-1-carboxylate	1507291: Inhibition of full length C-terminal FLAG tagged human SMS1 expressed in HEK293 cell membranes using DMPC-d72 and C17-ceramide as substrate preincubated for 60 mins followed by substrate addition measured after 30 mins by RapidFire/mass spectrometry assay	ic50	1.0000	uM
2-hydroxy-6-[(Z)-pentadec-8-enyl]benzoic acid	1600501: Inhibition of SMS1 (unknown origin)	ic50	1.5000	uM
1-(2,6-dihydroxyphenyl)-9-(3,4-dihydroxyphenyl)nonan-1-one	1600505: Noncompetitive inhibition of SMS1 (unknown origin) stably expressed in mouse ZS cells using 5 to 50 uM C6-NBD-ceramide as substrate preincubated for 30 mins followed by substrate addition and measured after 3 hrs by HPLC analysis	ic50	2.0000	uM
1-(2,6-dihydroxyphenyl)-9-(4-hydroxyphenyl)nonan-1-one	1600505: Noncompetitive inhibition of SMS1 (unknown origin) stably expressed in mouse ZS cells using 5 to 50 uM C6-NBD-ceramide as substrate preincubated for 30 mins followed by substrate addition and measured after 3 hrs by HPLC analysis	ic50	2.0000	uM
1-(2,6-dihydroxyphenyl)-9-phenylnonan-1-one	1600505: Noncompetitive inhibition of SMS1 (unknown origin) stably expressed in mouse ZS cells using 5 to 50 uM C6-NBD-ceramide as substrate preincubated for 30 mins followed by substrate addition and measured after 3 hrs by HPLC analysis	ic50	2.0000	uM
N-[(4-bromophenyl)methyl]-2-[4-(2-phenylethylsulfamoyl)phenoxy]acetamide	1245175: Inhibition of sphingomyelin synthase-1 (unknown origin) expressed in HeLa cells using C6-NBD-Cer and DMPC as substrate after 2 hrs by fluorescent HPLC-based analysis	ic50	2.1000	uM
(1-methylcyclopropyl) 4-[3-[[3-[[3-methoxy-5-(trifluoromethyl)phenyl]methyl-methylcarbamoyl]-1-methyl-2-oxo-1,8-naphthyridin-4-yl]oxy]propyl]piperidine-1-carboxylate	1667230: Inhibition of human recombinant C-terminal FLAG-tagged SMS1 expressed in mammalian expression system using C14-phosphatidylcholineD72 and C17-ceramide pre-incubated for 60 mins followed by incubation with substrate for 30 mins measured by RapidFire/MS assay	ic50	2.4000	uM
tert-butyl 4-[3-[3-[[3,5-bis(trifluoromethyl)phenyl]methyl-methylcarbamoyl]-1-methyl-2-oxoquinolin-4-yl]oxypropyl]piperidine-1-carboxylate	1667230: Inhibition of human recombinant C-terminal FLAG-tagged SMS1 expressed in mammalian expression system using C14-phosphatidylcholineD72 and C17-ceramide pre-incubated for 60 mins followed by incubation with substrate for 30 mins measured by RapidFire/MS assay	ic50	3.4000	uM
N-[(4-chlorophenyl)methyl]-2-[4-(2-phenylethylsulfamoyl)phenoxy]acetamide	1245175: Inhibition of sphingomyelin synthase-1 (unknown origin) expressed in HeLa cells using C6-NBD-Cer and DMPC as substrate after 2 hrs by fluorescent HPLC-based analysis	ic50	5.2000	uM
N-[(4-methoxyphenyl)methyl]-2-[4-(2-phenylethylsulfamoyl)phenoxy]acetamide	1245175: Inhibition of sphingomyelin synthase-1 (unknown origin) expressed in HeLa cells using C6-NBD-Cer and DMPC as substrate after 2 hrs by fluorescent HPLC-based analysis	ic50	5.9000	uM
9-(4-hydroxyphenyl)-1-(2,4,6-trihydroxyphenyl)nonan-1-one	1600503: Inhibition of SMS1 (unknown origin) stably expressed in mouse ZS cells using C6-NBD-ceramide as substrate preincubated for 30 mins followed by substrate addition and measured after 3 hrs by HPLC analysis	ic50	6.0000	uM
N-(4-chlorophenyl)-2-[4-(2-phenylethylsulfamoyl)phenoxy]acetamide	1245175: Inhibition of sphingomyelin synthase-1 (unknown origin) expressed in HeLa cells using C6-NBD-Cer and DMPC as substrate after 2 hrs by fluorescent HPLC-based analysis	ic50	6.6000	uM
N-[(4-fluorophenyl)methyl]-2-[4-(2-phenylethylsulfamoyl)phenoxy]acetamide	1245175: Inhibition of sphingomyelin synthase-1 (unknown origin) expressed in HeLa cells using C6-NBD-Cer and DMPC as substrate after 2 hrs by fluorescent HPLC-based analysis	ic50	8.1000	uM
N-(3-methoxyphenyl)-2-[4-(2-phenylethylsulfamoyl)phenoxy]acetamide	1245175: Inhibition of sphingomyelin synthase-1 (unknown origin) expressed in HeLa cells using C6-NBD-Cer and DMPC as substrate after 2 hrs by fluorescent HPLC-based analysis	ic50	9.2000	uM
tert-butyl 4-[3-[[3-[(3,5-dimethoxyphenyl)methyl-methylcarbamoyl]-1-methyl-2-oxo-1,8-naphthyridin-4-yl]oxy]propyl]piperidine-1-carboxylate	1667230: Inhibition of human recombinant C-terminal FLAG-tagged SMS1 expressed in mammalian expression system using C14-phosphatidylcholineD72 and C17-ceramide pre-incubated for 60 mins followed by incubation with substrate for 30 mins measured by RapidFire/MS assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, increases expression, decreases reaction, increases abundance	3
Valproic Acid	affects cotreatment, increases expression, decreases methylation	3
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases abundance	2
Air Pollutants	increases abundance, increases expression, decreases expression, affects cotreatment	2
Ozone	affects cotreatment, increases expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
ginger extract	decreases reaction, increases abundance, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
sodium arsenite	affects methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
cupric chloride	increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	affects cotreatment, decreases methylation	1
PCI 5002	affects cotreatment, increases expression	1
Bortezomib	increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Leflunomide	increases expression	1

ChEMBL screening assays

13 unique, capped per target: 10 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3614737	Binding	Inhibition of sphingomyelin synthase-1 (unknown origin) expressed in HeLa cells using C6-NBD-Cer and DMPC as substrate after 2 hrs by fluorescent HPLC-based analysis	Discovery, synthesis and biological evaluation of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) as novel sphingomyelin synthase 1 inhibitors. — Bioorg Med Chem
CHEMBL4139285	ADMET	Inhibition of full length C-terminal FLAG tagged human SMS1 expressed in HEK293 cell membranes using DMPC-d72 and C17-ceramide as substrate preincubated for 60 mins followed by substrate addition measured after 30 mins by RapidFire/mass spe	Discovery and characterization of selective human sphingomyelin synthase 2 inhibitors. — Eur J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0UX	Ubigene Hep G2 SGMS1 KO	Cancer cell line	Male
CVCL_E2JZ	HAP1 SGMS1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder