SPTLC1

Summary

SPTLC1 (serine palmitoyltransferase long chain base subunit 1, HGNC:11277) is a protein-coding gene on chromosome 9q22.31, encoding Serine palmitoyltransferase 1 (O15269). 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. It is a selective cancer dependency (DepMap: 80.8% of cell lines).

This gene encodes a member of the class-II pyridoxal-phosphate-dependent aminotransferase family. The encoded protein is the long chain base subunit 1 of serine palmitoyltransferase. Serine palmitoyltransferase converts L-serine and palmitoyl-CoA to 3-oxosphinganine with pyridoxal 5’-phosphate and is the key enzyme in sphingolipid biosynthesis. Mutations in this gene were identified in patients with hereditary sensory neuropathy type 1. Alternatively spliced variants encoding different isoforms have been identified. Pseudogenes of this gene have been defined on chromosomes 1, 6, 10, and 13.

Source: NCBI Gene 10558 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neuropathy, hereditary sensory and autonomic, type 1A (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 559 total — 7 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 110
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 80.8% of screened cell lines
• MANE Select transcript: NM_006415

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11277
Approved symbol	SPTLC1
Name	serine palmitoyltransferase long chain base subunit 1
Location	9q22.31
Locus type	gene with protein product
Status	Approved
Aliases	LCB1, SPTI, HSAN1, hLCB1
Ensembl gene	ENSG00000090054
Ensembl biotype	protein_coding
OMIM	605712
Entrez	10558

Gene structure

Transcript identifiers

Ensembl transcripts: 41 — 22 protein_coding, 12 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000262554, ENST00000337841, ENST00000461132, ENST00000469778, ENST00000477888, ENST00000482632, ENST00000488921, ENST00000642671, ENST00000643599, ENST00000644140, ENST00000646481, ENST00000646534, ENST00000686600, ENST00000686799, ENST00000687427, ENST00000687817, ENST00000687972, ENST00000689261, ENST00000689401, ENST00000689423, ENST00000690095, ENST00000690139, ENST00000692363, ENST00000692458, ENST00000693147, ENST00000884973, ENST00000884974, ENST00000884975, ENST00000884976, ENST00000884977, ENST00000884978, ENST00000913242, ENST00000913243, ENST00000913244, ENST00000913245, ENST00000953498, ENST00000953499, ENST00000953500, ENST00000953501, ENST00000953502, ENST00000953503

RefSeq mRNA: 5 — MANE Select: NM_006415 NM_001281303, NM_001368272, NM_001368273, NM_006415, NM_178324

CCDS: CCDS6692, CCDS6693

Canonical transcript exons

ENST00000262554 — 15 exons

Exon	Start	End
ENSE00000711158	92045999	92046053
ENSE00000711172	92055405	92055494
ENSE00000869997	92047613	92047708
ENSE00000869998	92047172	92047268
ENSE00000900659	92038248	92038365
ENSE00000900661	92049960	92050067
ENSE00001844829	92115314	92115413
ENSE00001922759	92031147	92032558
ENSE00003462145	92080016	92080088
ENSE00003471749	92034810	92034883
ENSE00003481914	92059179	92059308
ENSE00003619775	92067966	92068098
ENSE00003620957	92108740	92108834
ENSE00003673066	92112455	92112562
ENSE00003680898	92080870	92080963

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 98.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.9197 / max 66.4794, expressed in 1707 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101401	4.4293	1653
101402	1.4904	956

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
esophagus squamous epithelium	UBERON:0006920	98.49	gold quality
oral cavity	UBERON:0000167	98.10	gold quality
epithelium of esophagus	UBERON:0001976	98.05	gold quality
skin of hip	UBERON:0001554	97.96	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.55	gold quality
lower esophagus mucosa	UBERON:0035834	97.52	gold quality
calcaneal tendon	UBERON:0003701	97.50	gold quality
upper leg skin	UBERON:0004262	97.45	gold quality
colonic mucosa	UBERON:0000317	97.34	gold quality
germinal epithelium of ovary	UBERON:0001304	96.88	gold quality
choroid plexus epithelium	UBERON:0003911	96.83	gold quality
pharyngeal mucosa	UBERON:0000355	96.74	gold quality
mammalian vulva	UBERON:0000997	96.73	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.54	gold quality
placenta	UBERON:0001987	96.44	gold quality
corpus epididymis	UBERON:0004359	96.44	gold quality
palpebral conjunctiva	UBERON:0001812	96.43	gold quality
secondary oocyte	CL:0000655	96.42	gold quality
bronchial epithelial cell	CL:0002328	96.42	gold quality
jejunal mucosa	UBERON:0000399	96.41	gold quality
endometrium epithelium	UBERON:0004811	96.39	gold quality
penis	UBERON:0000989	96.38	gold quality
eye	UBERON:0000970	96.25	gold quality
islet of Langerhans	UBERON:0000006	96.21	gold quality
seminal vesicle	UBERON:0000998	96.17	gold quality
tibia	UBERON:0000979	96.07	gold quality
squamous epithelium	UBERON:0006914	96.05	gold quality
lower lobe of lung	UBERON:0008949	96.03	gold quality
caput epididymis	UBERON:0004358	96.01	gold quality
endometrium	UBERON:0001295	95.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

98 targeting SPTLC1, 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-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 80.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 36)

• an increase in transepidermal water loss is an obligatory trigger for the upregulation of serine palmitoyltransferase mRNA expression in human epidermis (PMID:12445191)
• A novel missense mutation in exon 13 of the SPTLC1 gene (c.1160G–>C; p.G387A) in twin sisters with a severe HSN I phenotype is reported. (PMID:15037712)
• SPT1 aggregation preceded cell death in hypoxia and represents the first evidence of acute protein aggregation during hypoxia. (PMID:15467453)
• Transgenic mouse lines that ubiquitously overexpress either wild-type or mutant SPTLC1 represent a novel mouse model of peripheral neuropathy and confirm the link between mutant SPT and neuronal dysfunction. (PMID:16210380)
• 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)
• serine palmitoyltransferase and ceramidase are two major ceramide metabolizing enzymes that may have roles in psoriatic epidermis (PMID:17982236)
• SPTLC1 mutational analysis reveals the C133W mutation, a mutation common in British hereditary sensory and autonomic neuropathy type I patients. (PMID:18018475)
• Physical interaction of ABCA1 and SPTLC1 results in reduction of ABCA1 activity and that inhibition of this interaction produces enhanced cholesterol efflux. (PMID:18484747)
• we show that none of the HSAN I mutations interferes with serine palmitoyltransferase complex formation; the G387A mutation is most likely not directly associated with Hereditary sensory neuropathy type 1 (PMID:19132419)
• SPT subunit 1 might be present also in focal adhesions and the nucleus. (PMID:19362163)
• discovery of 2 proteins, ssSPTa and ssSPTb, which each interacts with both hLCB1 and hLCB2, suggesting that there are 4 distinct human SPT isozymes. (PMID:19416851)
• Cell polarity factor Par3 binds SPTLC1 and modulates monocyte serine palmitoyltransferase activity and chemotaxis (PMID:19592499)
• Adult-onset hereditary sensory and autonomic neuropathy type (HSAN)I is the hypothetical result of a gain-of-function mutation in SPTLC1 that leads to accumulation of a toxic metabolite. (PMID:19923297)
• Hereditary sensory neuropathy type 1 is caused by a gain of function mutation in SPTLC1 which causes the accumulation of two neurotoxic sphingolipids (PMID:20097765)
• SPTLC1 mutations p.S331F and p.A352V result in a reduction of serine palmitoyltransferase activity in vitro and are associated with increased levels of the deoxysphingoid in patients’ plasma samples. (PMID:21618344)
• The p.CYS133Trp mutation in SPTLC1 is the most common cause of hereditary and autonomic neuropathy in the United Kingdom population. (PMID:22302274)
• Endoplasmic reticulum-resident human protein serine palmitoyltransferase long chain-1 (SPTLC1) is phosphorylated at Tyr(164) by the tyrosine kinase ABL. (PMID:23629659)
• Therefore, Ser331 in SPTLC1 is a crucial amino acid, which characterizes the Hereditary sensory and autonomic neuropathy type I phenotype (PMID:24247255)
• SPTLC1 mutations cause mitochondrial abnormalities and ER stress in HSN1 cells. (PMID:24673574)
• A novel SPTLC2-S384F variant in 2 unrelated HSAN1 families resulted in elevated plasma 1-deoxySL levels. Expression of this mutant in HEK293 cells increased 1-deoxySL formation. The substrate specificity is affected by phosphorylation at this position. (PMID:25567748)
• This study describe aberrant morphology of SPTLC1C133W Dorsal Root Ganglia characterized by increased neurite growth, branching, and expression of p-ERM at neuronal growth cones. (PMID:26446223)
• Hereditary sensory and autonomic neuropathy type 1 mutations in SPTLC1 have distinct biochemical properties, which allowed for the prediction of the clinical symptoms on the basis of the plasma sphingoid base profile. (PMID:26681808)
• Therefore, SPT may be an attractive therapeutic anti-cancer drug target for which compound-2 may be a promising new drug. (PMID:28108287)
• This study accomplished a cell-free reconstitution of the sphingolipid regulation of the ORMDL3-SPTLC1 complex to probe the underlying regulatory mechanism. Sphingolipid and ORMDL-dependent regulation of SPTLC1 was demonstrated in isolated membranes, essentially free of cytosol. This suggests that this regulation does not require soluble cytosolic proteins or small molecules such as ATP. (PMID:30700557)
• Elevated levels of atypical deoxysphingolipids, caused by variant SPTLC1 or SPTLC2 or by low serine levels, were risk factors for macular telangiectasia type 2, as well as for peripheral neuropathy. (PMID:31509666)
• Decreased SPTLC1 expression predicts worse outcomes in ccRCC patients. (PMID:31512789)
• Yhe results revealed that forced expression of SPTLC1 could significantly inhibit cell growth in vitro and in vivo via, at least in part, modulating Akt/FOXO1 signaling pathway, thus representing a novel role of SPTLC1 in the regulation of tumor growth in renal cell carcinoma (RCC). (PMID:31554600)
• Structural insights into the assembly and substrate selectivity of human SPT-ORMDL3 complex. (PMID:33558762)
• Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis. (PMID:34459874)
• Calcium-Mediated Calpain Activation and Microtubule Dissociation in Cell Model of Hereditary Sensory Neuropathy Type-1 Expressing V144D SPTLC1 Mutation. (PMID:34986032)
• New Insights into the Neuromyogenic Spectrum of a Gain of Function Mutation in SPTLC1. (PMID:35627278)
• The SPTLC1 p.S331 mutation bridges sensory neuropathy and motor neuron disease and has implications for treatment. (PMID:35904184)
• Pathogenic variants in the SPTLC1 gene cause hyperkeratosis lenticularis perstans. (PMID:36689507)
• Clinical feature difference between juvenile amyotrophic lateral sclerosis with SPTLC1 and FUS mutations. (PMID:36801857)
• Mutation screening of SPTLC1 and SPTLC2 in amyotrophic lateral sclerosis. (PMID:36966328)
• Functional and Molecular Characterization of New SPTLC1 Missense Variants in Patients with Hereditary Sensory and Autonomic Neuropathy Type 1 (HSAN1). (PMID:38927628)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sptlc1	ENSDARG00000042995
mus_musculus	Sptlc1	ENSMUSG00000021468
rattus_norvegicus	Sptlc1	ENSRNOG00000010882
drosophila_melanogaster	Spt-I	FBGN0086532
caenorhabditis_elegans		WBGENE00016020

Paralogs (5): ALAS1 (ENSG00000023330), GCAT (ENSG00000100116), SPTLC2 (ENSG00000100596), ALAS2 (ENSG00000158578), SPTLC3 (ENSG00000172296)

Protein

Protein identifiers

Serine palmitoyltransferase 1 — O15269 (reviewed: O15269)

Alternative names: Long chain base biosynthesis protein 1, Serine-palmitoyl-CoA transferase 1

All UniProt accessions (8): O15269, A0A2R8Y4S0, A0A2R8Y6A2, A0A2R8Y763, A0A8I5KUM4, A0A8I5KWE0, A0A8I5QJP4, A0A8I5QKQ8

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 also composed of SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer with SPTLC2 or 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. Required for adipocyte cell viability and metabolic homeostasis.

Subunit / interactions. Component of the serine palmitoyltransferase (SPT) complex, which is also composed of 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. Forms dimers of heterodimers with SPTLC2. Interacts with RTN4 (isoform B).

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed. Not detected in small intestine.

Post-translational modifications. Phosphorylation at Tyr-164 inhibits activity and promotes cell survival.

Disease relevance. Amyotrophic lateral sclerosis 27, juvenile (ALS27) [MIM:620285] A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. ALS27 is an autosomal dominant form manifesting as toe walking and gait abnormalities in early childhood. The disease is caused by variants affecting the gene represented in this entry. Variants associated with ALS27 tend to disrupt the normal homeostatic regulation of serine palmitoyltransferase (SPT) by ORMDL proteins, resulting in up-regulated SPT activity and elevated levels of canonical SPT products. Neuropathy, hereditary sensory and autonomic, 1A (HSAN1A) [MIM:162400] A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by prominent sensory abnormalities with a variable degree of motor and autonomic dysfunction. The neurological phenotype is often complicated by severe infections, osteomyelitis, and amputations. HSAN1A is an autosomal dominant axonal form with onset in the second or third decades. Initial symptoms are loss of pain, touch, heat, and cold sensation over the feet, followed by distal muscle wasting and weakness. Loss of pain sensation leads to chronic skin ulcers and distal amputations. The disease is caused by variants affecting the gene represented in this entry. Variants associated with HSAN1A tend to increase serine palmitoyltransferase (SPT) usage of alanine or glycine rather than serine, resulting in deoxysphingolipid synthesis. Deoxysphingolipids cannot be efficiently degraded by the cell machinery and cause cell toxicity.

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.

Domain organisation. The transmembrane domain is involved in the interaction with ORMDL3.

Induction. Expression at protein level is highly increased in brains of patients with Alzheimer disease. No changes are observed at mRNA level.

Pathway. Lipid metabolism; sphingolipid metabolism.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O15269-1	1	yes
O15269-2	2

RefSeq proteins (5): NP_001268232, NP_001355201, NP_001355202, NP_006406, NP_847894 (=MANE)

Domains & families (InterPro)

ID	Name	Type
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 (72 total): helix 21, strand 19, sequence variant 15, turn 5, mutagenesis site 4, topological domain 2, splice variant 2, chain 1, transmembrane region 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
7K0K	ELECTRON MICROSCOPY	2.6
7YIY	ELECTRON MICROSCOPY	2.7
7K0M	ELECTRON MICROSCOPY	2.9
7YIU	ELECTRON MICROSCOPY	2.9
7YJ2	ELECTRON MICROSCOPY	2.9
7K0J	ELECTRON MICROSCOPY	3.1
7K0N	ELECTRON MICROSCOPY	3.1
7K0O	ELECTRON MICROSCOPY	3.1
7K0P	ELECTRON MICROSCOPY	3.1
7YJ1	ELECTRON MICROSCOPY	3.1
7CQI	ELECTRON MICROSCOPY	3.2
7CQK	ELECTRON MICROSCOPY	3.3
7K0I	ELECTRON MICROSCOPY	3.3
7K0Q	ELECTRON MICROSCOPY	3.3
6M4O	ELECTRON MICROSCOPY	3.4
7K0L	ELECTRON MICROSCOPY	3.4
6M4N	ELECTRON MICROSCOPY	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15269-F1	94.04	0.86

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): 164

Mutagenesis-validated functional residues (4):

Position	Phenotype
138	decreased catalytic activity with l-serine and palmitoyl-coa as substrates.
164	increased serine palmitoyltransferase activity and sphingolipid content.
337	strongly decreased catalytic activity with l-serine and palmitoyl-coa as substrates.
338	decreased catalytic activity with l-serine and palmitoyl-coa as substrates.

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: 418 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, MORF_MBD4, YAGI_AML_WITH_INV_16_TRANSLOCATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, GOBP_SPHINGOMYELIN_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_POLYOL_METABOLIC_PROCESS, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1

GO Biological Process (11): sphingolipid metabolic process (GO:0006665), sphingomyelin biosynthetic process (GO:0006686), sphingolipid biosynthetic process (GO:0030148), sphinganine biosynthetic process (GO:0046511), sphingosine biosynthetic process (GO:0046512), ceramide biosynthetic process (GO:0046513), positive regulation of lipophagy (GO:1904504), regulation of fat cell apoptotic process (GO:1904649), lipid metabolic process (GO:0006629), biosynthetic process (GO:0009058), obsolete amide biosynthetic process (GO:0043604)

GO Molecular Function (5): serine C-palmitoyltransferase activity (GO:0004758), pyridoxal phosphate binding (GO:0030170), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), serine palmitoyltransferase complex (GO:0017059), 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
diol biosynthetic process	2
sphingoid biosynthetic process	2
lipid metabolic process	1
sphingomyelin metabolic process	1
phospholipid biosynthetic process	1
sphingolipid metabolic process	1
lipid biosynthetic process	1
sphinganine metabolic process	1
sphingosine metabolic process	1
ceramide metabolic process	1
positive regulation of macroautophagy	1
lipophagy	1
regulation of lipophagy	1
regulation of apoptotic process	1
fat cell apoptotic process	1
primary metabolic process	1
metabolic process	1
C-palmitoyltransferase activity	1
anion binding	1
vitamin B6 binding	1
binding	1
catalytic activity	1
transferase activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
palmitoyltransferase complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

2898 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPTLC1	SPTSSA	Q969W0	995
SPTLC1	SPTLC2	O15270	987
SPTLC1	SPTSSB	Q8NFR3	979
SPTLC1	ORM1	P02763	943
SPTLC1	ORMDL3	Q8N138	899
SPTLC1	ORMDL1	Q9P0S3	899
SPTLC1	SPTLC3	Q9NUV7	892
SPTLC1	ORMDL2	Q53FV1	886
SPTLC1	TLCD3B	Q71RH2	848
SPTLC1	UGCG	Q16739	845
SPTLC1	CERS6	Q6ZMG9	819
SPTLC1	SMPD1	P17405	817
SPTLC1	KDSR	Q06136	817
SPTLC1	CERK	Q8TCT0	815
SPTLC1	SMPD2	O60906	811

IntAct

149 interactions, top by confidence:

A	B	Type	Score
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
ORMDL3	SPTLC1	psi-mi:“MI:0915”(physical association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
IFT27	IFT56	psi-mi:“MI:0914”(association)	0.690
SPTLC1	SPTLC2	psi-mi:“MI:0915”(physical association)	0.680
SPTLC1	SPTLC2	psi-mi:“MI:0914”(association)	0.680
SPTLC2	SPTLC1	psi-mi:“MI:0914”(association)	0.680
SPTLC1	SPTSSA	psi-mi:“MI:0915”(physical association)	0.570
Zw10	NBAS	psi-mi:“MI:0914”(association)	0.560
RPN1	APBB1	psi-mi:“MI:0914”(association)	0.530
UNC93B1	GPR89A	psi-mi:“MI:0914”(association)	0.530
	SCD	psi-mi:“MI:0914”(association)	0.500
SPTLC3	SPTLC1	psi-mi:“MI:0914”(association)	0.480
SPTLC1	SPTLC3	psi-mi:“MI:0915”(physical association)	0.480
SPTLC1	SPTSSB	psi-mi:“MI:0915”(physical association)	0.370
SPTLC1	iglC2	psi-mi:“MI:0915”(physical association)	0.370
Mad2l1	MAD1L1	psi-mi:“MI:0914”(association)	0.350
Bub1	PEX10	psi-mi:“MI:0914”(association)	0.350
Bmpr1a	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Rab5b	BLTP3B	psi-mi:“MI:0914”(association)	0.350

BioGRID (241): SPTLC1 (Affinity Capture-MS), SPTLC1 (Affinity Capture-MS), SPTLC1 (Affinity Capture-MS), SPTLC1 (Affinity Capture-MS), SPTLC1 (Affinity Capture-MS), SPTLC1 (Affinity Capture-MS), SPTLC1 (Affinity Capture-MS), SPTLC1 (Affinity Capture-MS), SPTLC1 (Affinity Capture-MS), SPTLC1 (Affinity Capture-MS), SPTLC1 (Affinity Capture-MS), SPTLC1 (Affinity Capture-MS), SPTLC1 (Affinity Capture-MS), SPTLC1 (Affinity Capture-MS), SPTLC1 (Affinity Capture-MS)

ESM2 similar proteins: A2XLL2, A4IFH5, A7MBI7, D4A2H2, O15269, O54695, O97583, P11172, P13439, P24298, P25409, P47788, P52888, Q03426, Q10DK7, Q16773, Q1HAQ0, Q28DB5, Q3TFD2, Q3ZKN0, Q4V9J0, Q5E9M9, Q5E9T8, Q5R514, Q5R7A2, Q5R9T5, Q5U367, Q60714, Q60HD1, Q64323, Q6GM82, Q6NYL5, Q6P6M7, Q6PCB7, Q6SKR2, Q7TSA0, Q7XQ85, Q803A7, Q8BGT5, Q8CG45

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

1 interactions.

A	Effect	B	Mechanism
ABL1	down-regulates	SPTLC1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 160 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
PD-L1(CD274) glycosylation and translocation to plasma membrane	5	26.5×	2e-04
Sphingolipid de novo biosynthesis	6	17.5×	2e-04
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	5	17.1×	1e-03
Maturation of spike protein	6	16.3×	3e-04
Maturation of DENV proteins	7	15.1×	2e-04
MAPK6/MAPK4 signaling	6	8.3×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	5
Uncertain significance	301
Likely benign	172
Benign	14

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
2444011	NM_006415.4(SPTLC1):c.113T>G (p.Leu38Arg)	Pathogenic
246520	NM_006415.4(SPTLC1):c.58G>T (p.Ala20Ser)	Pathogenic
372788	NM_006415.4(SPTLC1):c.992C>A (p.Ser331Tyr)	Pathogenic
456600	NM_006415.4(SPTLC1):c.1015G>T (p.Ala339Ser)	Pathogenic
4800	NM_006415.4(SPTLC1):c.398G>A (p.Cys133Tyr)	Pathogenic
4803	NM_006415.4(SPTLC1):c.399T>G (p.Cys133Trp)	Pathogenic
4804	NM_006415.4(SPTLC1):c.992C>T (p.Ser331Phe)	Pathogenic
1308661	NM_006415.4(SPTLC1):c.986G>A (p.Arg329Gln)	Likely pathogenic
1917874	NM_006415.4(SPTLC1):c.398G>T (p.Cys133Phe)	Likely pathogenic
209194	NM_006415.4(SPTLC1):c.1072G>C (p.Glu358Gln)	Likely pathogenic
450572	NM_006415.4(SPTLC1):c.68A>T (p.Tyr23Phe)	Likely pathogenic
997832	NM_006415.4(SPTLC1):c.118_123del (p.Phe40_Ser41del)	Likely pathogenic

SpliceAI

3038 predictions. Top by Δscore:

Variant	Effect	Δscore
9:92032557:TG:T	acceptor_gain	1.0000
9:92032559:C:CC	acceptor_gain	1.0000
9:92034805:CTGA:C	donor_loss	1.0000
9:92034806:TGA:T	donor_loss	1.0000
9:92034807:GAC:G	donor_loss	1.0000
9:92034808:A:AG	donor_loss	1.0000
9:92034879:ATGCA:A	acceptor_gain	1.0000
9:92034880:TGCA:T	acceptor_gain	1.0000
9:92034881:GCA:G	acceptor_gain	1.0000
9:92034882:CA:C	acceptor_gain	1.0000
9:92034882:CAC:C	acceptor_gain	1.0000
9:92034883:ACTG:A	acceptor_loss	1.0000
9:92034884:C:CC	acceptor_gain	1.0000
9:92034884:C:T	acceptor_loss	1.0000
9:92034885:T:C	acceptor_loss	1.0000
9:92038242:ACTT:A	donor_loss	1.0000
9:92038243:CTT:C	donor_loss	1.0000
9:92038244:TTA:T	donor_loss	1.0000
9:92038245:TA:T	donor_loss	1.0000
9:92038246:A:AC	donor_gain	1.0000
9:92038246:ACTTG:A	donor_loss	1.0000
9:92038247:C:CT	donor_gain	1.0000
9:92038247:CTT:C	donor_gain	1.0000
9:92038247:CTTG:C	donor_gain	1.0000
9:92038247:CTTGA:C	donor_gain	1.0000
9:92038364:TG:T	acceptor_gain	1.0000
9:92038366:C:CC	acceptor_gain	1.0000
9:92045991:AAACT:A	donor_loss	1.0000
9:92045992:AACT:A	donor_loss	1.0000
9:92045993:ACT:A	donor_loss	1.0000

AlphaMissense

3073 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:92047242:A:C	F337L	1.000
9:92047242:A:T	F337L	1.000
9:92047244:A:G	F337L	1.000
9:92047267:C:G	R329P	1.000
9:92068007:A:C	S173R	1.000
9:92068007:A:T	S173R	1.000
9:92068009:T:G	S173R	1.000
9:92080024:C:T	G140D	1.000
9:92080029:A:C	F138L	1.000
9:92080029:A:T	F138L	1.000
9:92080031:A:G	F138L	1.000
9:92080042:C:T	G134E	1.000
9:92047234:G:C	S340W	0.999
9:92047237:G:T	A339D	0.999
9:92047243:A:C	F337C	0.999
9:92047243:A:G	F337S	0.999
9:92047244:A:C	F337V	0.999
9:92047244:A:T	F337I	0.999
9:92047245:G:C	C336W	0.999
9:92047252:C:T	G334E	0.999
9:92047253:C:G	G334R	0.999
9:92047253:C:T	G334R	0.999
9:92047258:C:T	G332D	0.999
9:92047259:C:G	G332R	0.999
9:92047264:A:G	L330P	0.999
9:92047618:G:C	H327D	0.999
9:92047638:C:T	G320D	0.999
9:92047643:G:C	C318W	0.999
9:92047645:A:G	C318R	0.999
9:92047650:C:T	G316D	0.999

dbSNP variants (sampled 300 via entrez): RS1000034893 (9:92114966 G>A,C), RS1000060569 (9:92097698 G>C), RS1000081951 (9:92051406 T>A), RS1000138954 (9:92031489 G>A), RS1000162455 (9:92091437 A>C,T), RS1000164041 (9:92105611 T>C), RS1000197766 (9:92077578 C>T), RS1000270809 (9:92112345 T>C), RS1000305900 (9:92105330 A>C,G), RS1000346211 (9:92100043 A>G), RS1000378591 (9:92061742 G>A), RS1000409421 (9:92061489 G>T), RS1000438179 (9:92088521 G>A), RS1000445570 (9:92106039 G>C), RS1000477271 (9:92075004 C>T)

Disease associations

OMIM: gene MIM:605712 | disease phenotypes: MIM:162400, MIM:620285, MIM:118220, MIM:619435

GenCC curated gene-disease

Disease	Classification	Inheritance
amyotrophic lateral sclerosis 27, juvenile	Strong	Autosomal dominant
neuropathy, hereditary sensory and autonomic, type 1A	Strong	Autosomal dominant
hereditary sensory and autonomic neuropathy type 1	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
neuropathy, hereditary sensory and autonomic, type 1A	Definitive	AD

Mondo (7): hereditary sensory and autonomic neuropathy type 1 (MONDO:0018213), neuropathy, hereditary sensory and autonomic, type 1A (MONDO:0008086), amyotrophic lateral sclerosis 27, juvenile (MONDO:0859529), Charcot-Marie-Tooth disease (MONDO:0015626), Ritscher-Schinzel syndrome 4 (MONDO:0030331), microcephaly (MONDO:0001149), amyotrophic lateral sclerosis (MONDO:0004976)

Orphanet (3): Hereditary sensory and autonomic neuropathy type 1 (Orphanet:36386), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Amyotrophic lateral sclerosis (Orphanet:803)

HPO phenotypes

110 total (30 of 110 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000252	Microcephaly
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000518	Cataract
HP:0000605	Supranuclear gaze palsy
HP:0000639	Nystagmus
HP:0000708	Atypical behavior
HP:0000726	Dementia
HP:0000962	Hyperkeratosis
HP:0001026	Penetrating foot ulcers
HP:0001058	Poor wound healing
HP:0001251	Ataxia
HP:0001263	Global developmental delay
HP:0001264	Spastic diplegia
HP:0001265	Hyporeflexia
HP:0001276	Hypertonia
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism
HP:0001308	Tongue fasciculations
HP:0001317	Abnormal cerebellum morphology
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0001761	Pes cavus
HP:0001868	Autoamputation of foot
HP:0001886	Foot osteomyelitis

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001567_13	Bipolar disorder and schizophrenia	6.000000e-07
GCST002554_2	Left inferior lateral ventricle volume (Cerebrospinal fluid biomarker status interaction)	3.000000e-10
GCST010146_11	Serum immune biomarker levels	3.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0006793	left inferior lateral ventricle volume measurement
EFO:0004869	YKL40 measurement
EFO:0004872	inflammatory biomarker measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000690	Amyotrophic Lateral Sclerosis	C10.228.854.139; C10.574.562.250; C10.574.950.050; C10.668.467.250; C18.452.845.800.050
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1250343 (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

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

Ligand	Action	Affinity	Parameter
myriocin	Inhibition	9.55	pKi

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.29	IC50	5.19	nM	CHEMBL4584997
8.00	IC50	10	nM	CHEMBL1241090
7.30	EC50	49.5	nM	MYRIOCIN
7.19	IC50	63.9	nM	CHEMBL4541898
6.97	Kd	106.9	nM	CHEMBL5653589
6.97	ED50	106.9	nM	CHEMBL5653589
6.21	Kd	613.2	nM	CHEMBL3752910
6.21	ED50	613.2	nM	CHEMBL3752910
6.01	EC50	977	nM	CHEMBL4584997
5.38	EC50	4220	nM	CHEMBL4541898

PubChem BioAssay actives

8 with measured affinity, of 13 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
2-[4-(6-heptanoylimidazo[1,2-a]pyridin-8-yl)phenyl]acetic acid	1635337: Inhibition of human SPT1 expressed in microsomes of HEK293 cells incubated for 1hr by LC/MS analysis	ic50	0.0052	uM
(2S)-2-[(E,2S)-1-[[(1S)-1-carboxy-2-[4-(3-methylbut-2-enoxy)phenyl]ethyl]amino]-1,11-dioxooctadec-3-en-2-yl]-2-hydroxybutanedioic acid	512654: Inhibition of human recombinant SPT1 activity in LCB1 transfected human HEK293 cells	ic50	0.0100	uM
(E,2S,3R,4R)-2-amino-3,4-dihydroxy-2-(hydroxymethyl)-14-oxoicos-6-enoic acid	1635338: Inhibition of SPT1 in human MCF7 cells assessed as suppression of 14C-serine incorporation into ceramide incubated for 2 hrs in presence of 4-HPR	ec50	0.0495	uM
2-[4-(5-heptanoyl-1-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridin-3-yl)phenyl]-2-methylpropanoic acid	1635337: Inhibition of human SPT1 expressed in microsomes of HEK293 cells incubated for 1hr by LC/MS analysis	ic50	0.0639	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149476: Binding affinity to human SPTLC1 incubated for 45 mins by Kinobead based pull down assay	kd	0.1069	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149476: Binding affinity to human SPTLC1 incubated for 45 mins by Kinobead based pull down assay	kd	0.6132	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, decreases reaction	2
sodium arsenite	increases abundance, decreases expression	2
bisphenol S	affects expression, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
thermozymocidin	decreases reaction, increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
kojic acid	increases expression	1
diethyl maleate	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(k)fluoranthene	decreases response to substance	1
perfluorooctanoic acid	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Arbutin	increases expression	1
Arsenic	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Clozapine	decreases expression	1
Coumestrol	increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Methylcholanthrene	affects localization, decreases reaction, increases expression, decreases response to substance	1
Ozone	affects expression, increases abundance	1
Tetrachlorodibenzodioxin	decreases response to substance	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1250174	Binding	Inhibition of human recombinant SPT1 activity in LCB1 transfected human HEK293 cells	Host sphingolipid biosynthesis as a target for hepatitis C virus therapy. — Nat Chem Biol

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TQ28	HAP1 SPTLC1 (-) 1	Cancer cell line	Male
CVCL_TQ29	HAP1 SPTLC1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00542412	PHASE4	COMPLETED	CARE Canadian ALS Riluzole Evaluation
NCT00560287	PHASE4	UNKNOWN	Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis
NCT00613899	PHASE4	COMPLETED	Feasibility of Telesurveillance and Home Cough Assistance for Amyotrophic Lateral Patients (ALS)
NCT04997954	PHASE4	UNKNOWN	EMERALD TRIAL Open Label Extension Study
NCT06849115	PHASE4	COMPLETED	Effects of L-Carnitine in Amyotrophic Lateral Sclerosis Patients With CHCHD10 Mutations
NCT07223723	PHASE4	RECRUITING	A Study to Learn More About the Long-Term Safety of Tofersen (Qalsody) in Chinese Participants With SOD-1 Amyotrophic Lateral Sclerosis (ALS)
NCT04762758	PHASE3	UNKNOWN	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
NCT00021697	PHASE3	COMPLETED	Safety/Efficacy of AVP-923 in the Treatment of Emotional Lability (Uncontrolled Crying & Laughing) in Patients With ALS
NCT00035815	PHASE3	COMPLETED	Insulin-like Growth Factor-1 in Amyotrophic Lateral Sclerosis (ALS) Trial
NCT00047723	PHASE3	COMPLETED	Minocycline to Treat Amyotrophic Lateral Sclerosis
NCT00069186	PHASE3	UNKNOWN	Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis
NCT00136110	PHASE3	COMPLETED	Trial of Sodium Valproate in Amyotrophic Lateral Sclerosis
NCT00330681	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS)
NCT00349622	PHASE3	COMPLETED	Clinical Trial Ceftriaxone in Subjects With ALS
NCT00372879	PHASE3	COMPLETED	Clinical Trial of Vitamin E to Treat Muscular Cramps in Patients With ALS
NCT00415519	PHASE3	COMPLETED	Efficacy and Safety Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis (ALS) Who Met Severity Classification III
NCT00424463	PHASE3	COMPLETED	Expanded Controlled Study of Safety and Efficacy of MCI-186 in Patients With Amyotrophic Lateral Sclerosis (ALS)
NCT00839033	PHASE3	TERMINATED	Evaluation of a Mechanical Device During Acute Respiratory Failure in Patients With Neuromuscular Disorders
NCT00868166	PHASE3	COMPLETED	Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
NCT00965497	PHASE3	COMPLETED	Escitalopram (Lexapro) for Depression MS or ALS
NCT01016522	PHASE3	TERMINATED	Safety and Tolerability of the Ketogenic Diet in Amyotrophic Lateral Sclerosis (ALS)
NCT01160263	PHASE3	COMPLETED	Study of Dopamine and Serotonin Transporters in Patients With Amyotrophic Lateral Sclerosis and Controls
NCT01281189	PHASE3	COMPLETED	Phase 3 Study of Dexpramipexole in ALS
NCT01492686	PHASE3	COMPLETED	Phase 3 Study of MCI-186 for Treatment of Amyotrophic Lateral Sclerosis
NCT01583088	PHASE3	TERMINATED	Early Stage Amyotrophic Lateral Sclerosis Phrenic Stimulation
NCT01622088	PHASE3	TERMINATED	Phase 3 Extension Study of Dexpramipexole in ALS
NCT02496767	PHASE3	COMPLETED	Ventilatory Investigation of Tirasemtiv and Assessment of Longitudinal Indices After Treatment for a Year
NCT02623699	PHASE3	COMPLETED	An Efficacy, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of BIIB067 (Tofersen) in Adults With Inherited Amyotrophic Lateral Sclerosis (ALS)
NCT02936635	PHASE3	COMPLETED	A Study for Patients Who Completed VITALITY-ALS (CY 4031)
NCT03127267	PHASE3	RECRUITING	Efficacy and Safety of Masitinib Versus Placebo in the Treatment of ALS Patients
NCT03280056	PHASE3	COMPLETED	Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients
NCT03491462	PHASE3	COMPLETED	Arimoclomol in Amyotropic Lateral Sclerosis
NCT03505021	PHASE3	COMPLETED	Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS
NCT03548311	PHASE3	COMPLETED	Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
NCT03690791	PHASE3	UNKNOWN	Efficacy of Cannabinoids in Amyotrophic Lateral Sclerosis or Motor Neurone Disease
NCT03800524	PHASE3	UNKNOWN	Safety and Efficacy of TUDCA as add-on Treatment in Patients Affected by ALS
NCT03836716	PHASE3	TERMINATED	Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
NCT03948178	PHASE3	TERMINATED	Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
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