SPTLC3

Summary

SPTLC3 (serine palmitoyltransferase long chain base subunit 3, HGNC:16253) is a protein-coding gene on chromosome 20p12.1, encoding Serine palmitoyltransferase 3 (Q9NUV7). Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases.

This gene encodes a subunit of the serine palmitoyltransferase complex which catalyzes the rate-limiting step in sphingolipid biosynthesis. This subunit metabolizes lauroyl- and myristoyl-CoA and generates C14 and C16-sphingoid bases.

Source: NCBI Gene 55304 — RefSeq curated summary.

At a glance

• GWAS associations: 71
• Clinical variants (ClinVar): 80 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_018327

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16253
Approved symbol	SPTLC3
Name	serine palmitoyltransferase long chain base subunit 3
Location	20p12.1
Locus type	gene with protein product
Status	Approved
Aliases	LCB2B, FLJ11112, hLCB2b
Ensembl gene	ENSG00000172296
Ensembl biotype	protein_coding
OMIM	611120
Entrez	55304

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000399002, ENST00000431275, ENST00000434210, ENST00000450297, ENST00000476791, ENST00000485952, ENST00000966145

RefSeq mRNA: 2 — MANE Select: NM_018327 NM_001349945, NM_018327

CCDS: CCDS13115

Canonical transcript exons

ENST00000399002 — 12 exons

Exon	Start	End
ENSE00001623090	13164754	13169103
ENSE00001651073	13074349	13074497
ENSE00001656660	13117506	13117725
ENSE00001686550	13072256	13072410
ENSE00001690600	13160003	13160132
ENSE00001692378	13048945	13049130
ENSE00001786162	13091083	13091207
ENSE00001791279	13110112	13110217
ENSE00001800664	13093484	13093577
ENSE00001930212	13008972	13009384
ENSE00003582396	13154003	13154138
ENSE00003613614	13126591	13126717

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 95.79.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.7451 / max 455.0592, expressed in 1083 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183600	3.8413	942
183603	0.8048	322
183599	0.4035	208
183604	0.2964	111
183605	0.2735	111
208998	0.0684	20
183602	0.0396	9
183601	0.0177	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	95.79	gold quality
placenta	UBERON:0001987	90.23	gold quality
skin of abdomen	UBERON:0001416	88.11	gold quality
skin of leg	UBERON:0001511	87.90	gold quality
calcaneal tendon	UBERON:0003701	86.58	gold quality
zone of skin	UBERON:0000014	85.93	gold quality
sural nerve	UBERON:0015488	85.29	gold quality
right lobe of thyroid gland	UBERON:0001119	84.63	gold quality
left lobe of thyroid gland	UBERON:0001120	83.85	gold quality
thyroid gland	UBERON:0002046	83.80	gold quality
gall bladder	UBERON:0002110	82.15	gold quality
upper leg skin	UBERON:0004262	82.10	gold quality
tendon	UBERON:0000043	82.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.41	gold quality
right lobe of liver	UBERON:0001114	80.76	gold quality
metanephros cortex	UBERON:0010533	80.16	gold quality
adrenal tissue	UBERON:0018303	78.98	gold quality
rectum	UBERON:0001052	78.72	gold quality
visceral pleura	UBERON:0002401	78.22	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.09	gold quality
endometrium	UBERON:0001295	77.91	gold quality
tendon of biceps brachii	UBERON:0008188	76.98	gold quality
liver	UBERON:0002107	76.82	gold quality
adult mammalian kidney	UBERON:0000082	76.72	gold quality
tibial nerve	UBERON:0001323	76.70	gold quality
vagina	UBERON:0000996	76.02	gold quality
tibia	UBERON:0000979	75.99	gold quality
duodenum	UBERON:0002114	75.88	gold quality
right lung	UBERON:0002167	75.65	gold quality
upper arm skin	UBERON:0004263	75.27	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	20.36
E-ANND-3	yes	10.37
E-GEOD-130473	no	451.63
E-MTAB-7381	no	182.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

120 targeting SPTLC3, 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-6867-5P	100.00	82.21	3464
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-345-3P	99.89	70.23	1421

Literature-anchored findings (GeneRIF, showing 8)

• cloning and expression in tissues and cell lines (PMID:17023427)
• Results suggest that functional serine palmitoyltransferase is not a dimer, but a higher organized complex, composed of three distinct subunits (SPTLC1, SPTLC2 and SPTLC3) with a molecular mass of 480 kDa. (PMID:17331073)
• Data show that the SPTLC3 subunit generates C(16)-sphingoid bases and that sphingolipids with a C(16) backbone constitute a significant proportion of plasma sphingolipids. (PMID:19648650)
• Data identified LC3B globular structures in esophageal adenocarcinoma patients strongly associated with patient outcome irrespective of treatment. (PMID:26265176)
• The association between the SPTLC3 rs364585 SNP and serum total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels in the Han and Jing populations (PMID:28056980)
• This study demonstrated that the association of SPTLC3insACAC (p = 0.055) with the treatment-resistant ophthalmoplegic subphenotype of myasthenia gravis. (PMID:28673556)
• The associations between individual plasma SFAs, serine palmitoyl-transferase long-chain base subunit 3 gene rs680379 polymorphism, and type 2 diabetes among Chinese adults. (PMID:33964854)
• Serine Palmitoyltransferase Subunit 3 and Metabolic Diseases. (PMID:35503173)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sptlc3	ENSDARG00000030743
mus_musculus	Sptlc3	ENSMUSG00000039092
rattus_norvegicus	Sptlc3	ENSRNOG00000004443

Paralogs (5): ALAS1 (ENSG00000023330), SPTLC1 (ENSG00000090054), GCAT (ENSG00000100116), SPTLC2 (ENSG00000100596), ALAS2 (ENSG00000158578)

Protein

Protein identifiers

Serine palmitoyltransferase 3 — Q9NUV7 (reviewed: Q9NUV7)

Alternative names: Long chain base biosynthesis protein 2b, Long chain base biosynthesis protein 3, Serine-palmitoyl-CoA transferase 3

All UniProt accessions (4): B1AKS2, B1AKS3, Q9NUV7, H0Y733

UniProt curated annotations — full annotation on UniProt →

Function. Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core. The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA. The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference.

Subunit / interactions. Component of the serine palmitoyltransferase (SPT) complex, which is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. The heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or SPTSSB subunits determine substrate specificity. SPT also interacts with ORMDL proteins, especially ORMDL3, which negatively regulate SPT activity in the presence of ceramides.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in most tissues, except peripheral blood cells and bone marrow, with highest levels in heart, kidney, liver, uterus and skin.

Activity regulation. SPT complex catalytic activity is negatively regulated by ORMDL proteins, including ORMDL3, in the presence of ceramides. This mechanism allows to maintain ceramide levels at sufficient concentrations for the production of complex sphingolipids, but which prevents the accumulation of ceramides to levels that trigger apoptosis.

Pathway. Lipid metabolism; sphingolipid metabolism.

Similarity. Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NUV7-1	1	yes
Q9NUV7-2	2

RefSeq proteins (2): NP_001336874, NP_060797* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001917	Aminotrans_II_pyridoxalP_BS	Binding_site
IPR004839	Aminotransferase_I/II_large	Domain
IPR015421	PyrdxlP-dep_Trfase_major	Homologous_superfamily
IPR015422	PyrdxlP-dep_Trfase_small	Homologous_superfamily
IPR015424	PyrdxlP-dep_Trfase	Homologous_superfamily
IPR050087	AON_synthase_class-II	Family

Pfam: PF00155

Enzyme classification (BRENDA):

• EC 2.3.1.50 — serine C-palmitoyltransferase (BRENDA: 23 organisms, 127 substrates, 64 inhibitors, 70 Km, 38 kcat entries)

Substrate kinetics (BRENDA)

13 substrates with measured Km, best-characterized 13. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-SERINE	0.26–10.6	28
PALMITOYL-COA	0.019–1.2	18
MYRISTOYL-COA	0.03–0.097	3
CAPROYL-COA	0.68–0.9	2
L-ALANINE	9.6–110	2
LAUROYL-COA	0.25–0.56	2
GLYCINE	77	1
L-HOMOSERINE	82	1
STEAROYL-COA	0.0129	1
[1,2,3-13C,2-15N] L-SERINE	1.79	1
[2,3,3-D] L-SERINE	4.09	1
[2-13C] L-SERINE	3.64	1
[3,3-D] L-SERINE	2.72	1

Catalyzed reactions (Rhea), 4 shown:

• L-serine + hexadecanoyl-CoA + H(+) = 3-oxosphinganine + CO2 + CoA (RHEA:14761)
• octadecanoyl-CoA + L-serine + H(+) = 3-oxoeicosasphinganine + CO2 + CoA (RHEA:33683)
• tetradecanoyl-CoA + L-serine + H(+) = 3-oxohexadecasphinganine + CO2 + CoA (RHEA:35675)
• dodecanoyl-CoA + L-serine + H(+) = 3-oxotetradecasphinganine + CO2 + CoA (RHEA:35679)

UniProt features (8 total): splice variant 2, sequence variant 2, chain 1, transmembrane region 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NUV7-F1	87.25	0.76

Functional residue map

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

Post-translational modifications (1): 371

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: 113 (showing top): GOBP_POLYOL_METABOLIC_PROCESS, GOBP_CERAMIDE_BIOSYNTHETIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_SPHINGOID_METABOLIC_PROCESS, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, GOBP_DIOL_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_CERAMIDE_METABOLIC_PROCESS, REACTOME_SPHINGOLIPID_METABOLISM, GOBP_SPHINGOLIPID_BIOSYNTHETIC_PROCESS, HAN_SATB1_TARGETS_DN, GOBP_MEMBRANE_LIPID_METABOLIC_PROCESS

GO Biological Process (7): sphingolipid biosynthetic process (GO:0030148), sphingosine biosynthetic process (GO:0046512), ceramide biosynthetic process (GO:0046513), sphingoid biosynthetic process (GO:0046520), lipid metabolic process (GO:0006629), sphingolipid metabolic process (GO:0006665), biosynthetic process (GO:0009058)

GO Molecular Function (6): serine C-palmitoyltransferase activity (GO:0004758), pyridoxal phosphate binding (GO:0030170), protein binding (GO:0005515), transaminase activity (GO:0008483), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (4): endoplasmic reticulum membrane (GO:0005789), serine palmitoyltransferase complex (GO:0017059), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

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
sphingolipid biosynthetic process	2
sphingolipid metabolic process	1
lipid biosynthetic process	1
sphingosine metabolic process	1
diol biosynthetic process	1
sphingoid biosynthetic process	1
ceramide metabolic process	1
sphingoid metabolic process	1
primary metabolic process	1
lipid metabolic process	1
metabolic process	1
C-palmitoyltransferase activity	1
anion binding	1
vitamin B6 binding	1
binding	1
transferase activity, transferring nitrogenous groups	1
catalytic activity	1
transferase activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
palmitoyltransferase complex	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1764 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPTLC3	SPTSSA	Q969W0	978
SPTLC3	SPTSSB	Q8NFR3	975
SPTLC3	ORM1	P02763	912
SPTLC3	SPTLC1	O15269	892
SPTLC3	ORMDL3	Q8N138	890
SPTLC3	ORMDL1	Q9P0S3	875
SPTLC3	ORMDL2	Q53FV1	853
SPTLC3	TLCD3B	Q71RH2	846
SPTLC3	CERS4	Q9HA82	839
SPTLC3	UGCG	Q16739	822
SPTLC3	SMPD1	P17405	794
SPTLC3	KDSR	Q06136	790
SPTLC3	SMPD2	O60906	787
SPTLC3	CERK	Q8TCT0	786
SPTLC3	SPHK1	Q9NYA1	768

IntAct

10 interactions, top by confidence:

A	B	Type	Score
SPTLC3	SPTLC1	psi-mi:“MI:0914”(association)	0.480
SPTLC1	SPTLC3	psi-mi:“MI:0915”(physical association)	0.480
SPTLC3	SPTSSB	psi-mi:“MI:0915”(physical association)	0.480
SPTLC3	SPTSSA	psi-mi:“MI:0915”(physical association)	0.480
COQ6	NDUFAB1	psi-mi:“MI:0914”(association)	0.350
SPTLC3	POTEF	psi-mi:“MI:0914”(association)	0.350
PTH2R	SPTLC2	psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): SPTLC3 (Affinity Capture-RNA), SPTLC3 (Affinity Capture-RNA), LRRC15 (Affinity Capture-MS), SELENBP1 (Affinity Capture-MS), VSIG8 (Affinity Capture-MS), POTEF (Affinity Capture-MS), DUSP14 (Affinity Capture-MS), SPTLC3 (Affinity Capture-MS), SPTLC3 (Affinity Capture-MS), SPTLC3 (Affinity Capture-RNA)

ESM2 similar proteins: A0A2H5AIY0, A8XKT0, O13940, O14092, O15270, O54694, O59682, O95470, O96567, P05031, P24785, P34106, P40970, P48241, P52894, P78698, P91079, P97363, Q05567, Q09925, Q10P01, Q18026, Q20375, Q2R3K3, Q3B7D2, Q52RG7, Q54EX5, Q5JK39, Q5R4G0, Q6FXE3, Q6K8E7, Q75DX7, Q7G4P2, Q7SY54, Q8BG54, Q8BWU8, Q8CHN6, Q8R0X7, Q8RYL0, Q8RYL1

Diamond homologs: A0RIB9, A2SD53, A3DBD5, A5G6I9, A6LMP4, A6TU88, A7BFV6, A7BFV7, A7BFV8, A7HG96, A7HMM1, A7LXM2, A7Z4X1, A8MEX7, A9W106, B0C205, B0K590, B0KC20, B0SZS9, B1I4F9, B1Z7Y8, B4UCB1, B5EEV8, B5ELF7, B7HAZ0, B7ID58, B7IWN1, B7J3Y7, B7JLX2, B7L0L2, B8GVE2, B8J637, B9M8U3, D4A2H2, O15269, O15270, O35704, O54694, O54695, O59682

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	69
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
243088	NM_018327.4(SPTLC3):c.448T>C (p.Trp150Arg)	Likely pathogenic

SpliceAI

2362 predictions. Top by Δscore:

Variant	Effect	Δscore
20:13048944:GC:G	acceptor_gain	1.0000
20:13048944:GCA:G	acceptor_gain	1.0000
20:13048944:GCAA:G	acceptor_gain	1.0000
20:13048944:GCAAA:G	acceptor_gain	1.0000
20:13074493:AATGG:A	donor_gain	1.0000
20:13074494:ATGG:A	donor_gain	1.0000
20:13074494:ATGGG:A	donor_loss	1.0000
20:13074495:TGG:T	donor_gain	1.0000
20:13074495:TGGGT:T	donor_loss	1.0000
20:13074496:GG:G	donor_gain	1.0000
20:13074496:GGG:G	donor_gain	1.0000
20:13074497:GG:G	donor_gain	1.0000
20:13074497:GGTA:G	donor_loss	1.0000
20:13074498:G:GG	donor_gain	1.0000
20:13074499:T:G	donor_loss	1.0000
20:13091079:GCAG:G	acceptor_loss	1.0000
20:13091080:CA:C	acceptor_loss	1.0000
20:13091081:A:AG	acceptor_gain	1.0000
20:13091081:AG:A	acceptor_gain	1.0000
20:13091082:G:A	acceptor_loss	1.0000
20:13091082:G:GC	acceptor_gain	1.0000
20:13091082:GG:G	acceptor_gain	1.0000
20:13091205:AAGGT:A	donor_loss	1.0000
20:13091206:AGGTG:A	donor_loss	1.0000
20:13091207:GGTGA:G	donor_loss	1.0000
20:13091208:GTGA:G	donor_loss	1.0000
20:13094589:G:GT	donor_gain	1.0000
20:13154134:GTAGC:G	donor_gain	1.0000
20:13154137:GC:G	donor_gain	1.0000
20:13154139:G:GG	donor_gain	1.0000

AlphaMissense

3627 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:13091166:T:C	F231L	0.996
20:13091168:C:A	F231L	0.996
20:13091168:C:G	F231L	0.996
20:13093513:C:A	N254K	0.994
20:13093513:C:G	N254K	0.994
20:13160055:T:C	F490L	0.994
20:13160057:T:A	F490L	0.994
20:13160057:T:G	F490L	0.994
20:13091177:C:A	N234K	0.992
20:13091177:C:G	N234K	0.992
20:13117591:A:C	S340R	0.992
20:13117593:T:A	S340R	0.992
20:13117593:T:G	S340R	0.992
20:13117685:A:T	K371I	0.992
20:13049057:G:A	G77D	0.991
20:13093499:A:C	S250R	0.991
20:13093501:T:A	S250R	0.991
20:13093501:T:G	S250R	0.991
20:13074382:C:A	N164K	0.990
20:13074382:C:G	N164K	0.990
20:13093491:T:C	L247P	0.990
20:13093503:A:T	D251V	0.990
20:13126624:A:C	S396R	0.990
20:13126626:T:A	S396R	0.990
20:13126626:T:G	S396R	0.990
20:13072328:T:A	W126R	0.989
20:13072328:T:C	W126R	0.989
20:13074479:A:C	S197R	0.989
20:13074481:C:A	S197R	0.989
20:13074481:C:G	S197R	0.989

dbSNP variants (sampled 300 via entrez): RS1000004749 (20:13156326 C>G,T), RS1000019462 (20:13119602 G>A), RS1000026967 (20:13129482 C>G), RS1000030069 (20:13045929 A>G), RS1000038719 (20:13129675 T>A), RS1000105183 (20:13078266 C>A), RS1000117268 (20:13084812 T>C), RS1000117783 (20:13093471 G>C), RS1000126114 (20:13018569 A>G,T), RS1000170690 (20:13093719 G>A,C), RS1000174653 (20:13159764 G>A,T), RS1000193639 (20:13065588 A>C,G), RS1000194553 (20:13074967 T>C), RS1000221872 (20:13136254 A>C), RS1000224198 (20:13151859 A>C)

Disease associations

OMIM: gene MIM:611120 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): sensory peripheral neuropathy (MONDO:0002321), peripheral neuropathy (MONDO:0005244)

Orphanet (0):

HPO phenotypes

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

GWAS associations

71 associations (top):

Study	Trait	p-value
GCST000493_4	Sphingolipid levels	8.000000e-15
GCST000995_1	Personality traits in bipolar disorder	8.000000e-07
GCST001413_6	Sphingolipid levels	2.000000e-16
GCST001753_3	Body mass index (alcohol intake interaction)	4.000000e-06
GCST002222_49	LDL cholesterol	4.000000e-10
GCST002689_4	Very long-chain saturated fatty acid levels (fatty acid 24:0)	6.000000e-06
GCST002690_18	Very long-chain saturated fatty acid levels (fatty acid 20:0)	6.000000e-13
GCST003075_64	Cognitive decline rate in late mild cognitive impairment	1.000000e-06
GCST003075_77	Cognitive decline rate in late mild cognitive impairment	1.000000e-06
GCST003518_10	Daytime sleep phenotypes	3.000000e-07
GCST003518_12	Daytime sleep phenotypes	3.000000e-06
GCST004233_15	LDL cholesterol levels	4.000000e-11
GCST004580_3	Body mass index (recreational physical activity interaction)	3.000000e-06
GCST005575_33	Moyamoya disease	8.000000e-10
GCST005650_10	Serum metabolite ratios in chronic kidney disease	5.000000e-16
GCST005650_4	Serum metabolite ratios in chronic kidney disease	4.000000e-16
GCST005650_5	Serum metabolite ratios in chronic kidney disease	2.000000e-12
GCST005650_6	Serum metabolite ratios in chronic kidney disease	2.000000e-15
GCST005650_7	Serum metabolite ratios in chronic kidney disease	6.000000e-14
GCST005650_8	Serum metabolite ratios in chronic kidney disease	6.000000e-15
GCST005650_9	Serum metabolite ratios in chronic kidney disease	5.000000e-14
GCST008169_11	Benign prostatic hyperplasia	2.000000e-06
GCST008169_5	Benign prostatic hyperplasia	1.000000e-06
GCST008923_2	Ceramide levels	2.000000e-09
GCST008923_3	Ceramide levels	3.000000e-09
GCST008923_4	Ceramide levels	9.000000e-10
GCST008923_6	Ceramide levels	1.000000e-09
GCST009391_1420	Metabolite levels	2.000000e-06
GCST009391_535	Metabolite levels	4.000000e-06
GCST009698_103	Metabolite levels	5.000000e-11

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004365	personality trait
EFO:0004340	body mass index
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0007710	cognitive decline measurement
EFO:0007828	daytime rest measurement
EFO:0008002	physical activity measurement
EFO:0010452	adenosine diphosphate measurement
EFO:0010528	quinolinic acid measurement
EFO:0010118	sphingomyelin measurement
EFO:0004531	urate measurement
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066332 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Serine palmitoyltransferase

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.10	IC50	0.8	nM	CHEMBL5561881
8.80	IC50	1.6	nM	CHEMBL4225519
8.40	IC50	4	nM	CHEMBL5565596

PubChem BioAssay actives

3 with measured affinity, of 3 total; 3 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[(7S)-1-[5-[3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)propanoylamino]pentyl]-4-(3,4-dimethoxybenzoyl)-6,7-dihydro-5H-pyrazolo[4,5-b]pyridin-7-yl]-2-(trifluoromethoxy)benzamide	2084121: Inhibition of SPTLC3 (unknown origin)	ic50	0.0008	uM
N-[(7S)-4-(5,6-dimethoxypyridine-3-carbonyl)-1-propan-2-yl-6,7-dihydro-5H-pyrazolo[4,5-b]pyridin-7-yl]-2-(trifluoromethoxy)benzamide	2084121: Inhibition of SPTLC3 (unknown origin)	ic50	0.0016	uM
2-chloro-N-[(7S)-4-(3,4-dimethoxybenzoyl)-1-propan-2-yl-6,7-dihydro-5H-pyrazolo[4,5-b]pyridin-7-yl]benzamide	2084121: Inhibition of SPTLC3 (unknown origin)	ic50	0.0040	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	5
Valproic Acid	affects cotreatment, increases expression	5
Aflatoxin B1	decreases expression, affects expression, affects cotreatment	5
Tetrachlorodibenzodioxin	decreases expression, increases expression	4
Cyclosporine	decreases expression	3
bisphenol A	affects expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Air Pollutants	increases abundance, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
beta-Naphthoflavone	affects cotreatment, decreases expression	2
tremortin	decreases expression	1
deoxynivalenol	decreases expression	1
trichostatin A	increases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	decreases expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
azaspiracid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Leflunomide	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5524594	Binding	Inhibition of SPTLC3 (unknown origin)	Modulators for palmitoylation of proteins and small molecules. — Eur J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00380965	PHASE4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Chemotherapy-Induced Neuropathy
NCT00487981	PHASE4	TERMINATED	Spinal Cord Stimulation for Painful Diabetic Neuropathy
NCT00904202	PHASE4	COMPLETED	A Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01192113	PHASE4	COMPLETED	Safety and Efficacy of Mecobalamin Injection in Peripheral Neuropathies Patients (Study JGAZSY091109)
NCT01373983	PHASE4	COMPLETED	Intrathecal Bolus Doses of Ziconotide
NCT01458015	PHASE4	TERMINATED	Tapentadol Versus Oxycodone - a Mechanism-based Treatment Approach in Neuropathic Pain
NCT02074267	PHASE4	COMPLETED	Clinical Study for Assessment of the Efficacy of Gabapentin (Carbatin and Neurontin) in Patients With Neuropathy Pain
NCT02372149	PHASE4	UNKNOWN	IVIg for Demyelination in Diabetes Mellitus
NCT02670161	PHASE4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT07022938	PHASE4	COMPLETED	Nutritional Supplement for Treating Chemotherapy Induced Neuropathy
NCT07025005	PHASE4	RECRUITING	Fenofibrate Role in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone (VRd) Protocol in the Treatment of Patients With Multiple Myeloma (MM)
NCT01526564	PHASE3	COMPLETED	Clinical Study on Acetyl-L-Carnitine
NCT00058071	PHASE3	COMPLETED	Amifostine in Treating Peripheral Neuropathy in Patients Who Have Received Chemotherapy for Cancer
NCT00125268	PHASE3	TERMINATED	Near Infrared Light for the Treatment of Painful Peripheral Neuropathy
NCT00195013	PHASE3	COMPLETED	Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy
NCT00232141	PHASE3	COMPLETED	Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy
NCT00264875	PHASE3	COMPLETED	Open Label Safety And Efficacy Study Of Pregabalin In Subjects With Nerve Pain Asociated With Human Immunodeficiency Virus (HIV) Neuropathy
NCT00369564	PHASE3	COMPLETED	Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
NCT00471445	PHASE3	COMPLETED	Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
NCT00489411	PHASE3	COMPLETED	Duloxetine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
NCT00710554	PHASE3	COMPLETED	A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
NCT00711880	PHASE3	COMPLETED	A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia.
NCT00713323	PHASE3	COMPLETED	A Study to Compare the Safety and Tolerability of Sativex® in Patients With Neuropathic Pain.
NCT00713817	PHASE3	COMPLETED	A Study to Determine the Maintenance of Effect After Long-term Treatment of Sativex® in Subjects With Neuropathic Pain
NCT00775645	PHASE3	COMPLETED	S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo
NCT00872352	PHASE3	UNKNOWN	Evaluation of Bortezomib Induced Peripheral Neuropathy of Multiple Myeloma (MM) Patients
NCT00998738	PHASE3	TERMINATED	Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer
NCT01049217	PHASE3	TERMINATED	Pregabalin Versus Placebo In The Treatment Of Neuropathic Pain Associated With HIV Neuropathy
NCT01099449	PHASE3	COMPLETED	Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy
NCT01288937	PHASE3	TERMINATED	A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain
NCT01492920	PHASE3	WITHDRAWN	Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy
NCT01775449	PHASE3	COMPLETED	Prevention of Oxaliplatin-induced Neuropathic Pain by a Specific Diet
NCT02024191	PHASE3	UNKNOWN	The Role of Glutamine for Preventing Oxaliplatin-Induced Peripheral Neuropathy
NCT02217267	PHASE3	COMPLETED	Long Term Outcome After Serial Lidocaine Infusion in Peripheral Neuropathic Pain
NCT02294149	PHASE3	UNKNOWN	Vit D3 and Omega 3 in Chemo Induced Neuropathy
NCT02311907	PHASE3	COMPLETED	Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer
NCT06071936	PHASE3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06071975	PHASE3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
NCT06071988	PHASE3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06072573	PHASE3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy