SPTLC1

serine palmitoyltransferase long chain base subunit 1

Basic information

Region (hg38): 9:92000087-92115413

Previous symbols: [ "HSN1" ]

Links

ENSG00000090054 ∙ NCBI:10558 ∙ OMIM:605712 ∙ HGNC:11277 ∙ Uniprot:O15269 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary sensory and autonomic neuropathy type 1 (Supportive), mode of inheritance: AD
• amyotrophic lateral sclerosis 27, juvenile (Strong), mode of inheritance: AD
• neuropathy, hereditary sensory and autonomic, type 1A (Strong), mode of inheritance: AD
• amyotrophic lateral sclerosis 27, juvenile (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neuropathy, hereditary sensory and autonomic, type IA; Neuropathy, hereditary sensory and autonomic, type IC	AD	Neurologic	The condition involves sensory neuropathy with variable autonomic and motor involvement, and medical management (eg, with oral serine supplementation) has been reported as resulting in laboratory-based and clinical benefits	Neurologic	11242106; 11242114; 12417569; 15037712; 19132419; 20920666; 22045570; 22302274; 30626650; 31509666; 34059824; 34459874; 36204986

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPTLC1 gene.

• Hereditary sensory and autonomic neuropathy type 1 (4 variants)
• Neuropathy, hereditary sensory and autonomic, type 1A (3 variants)
• Charcot-Marie-Tooth disease (3 variants)
• Amyotrophic lateral sclerosis 27, juvenile (2 variants)
• Neuropathy, hereditary sensory and autonomic, type IA, severe (2 variants)
• not provided (2 variants)
• Sensorimotor neuropathy (1 variants)
• Inborn genetic diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPTLC1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	62	2	68
missense	6	5	162	6	1	180
nonsense			13			13
start loss			2			2
frameshift			10			10
inframe indel		2	3			5
splice donor/acceptor (+/-2bp)			8			8
splice region			17	22	1	40
non coding			13	54	12	79
Total	6	7	215	122	15

Variants in SPTLC1

This is a list of pathogenic ClinVar variants found in the SPTLC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-92031158-G-A		Neuropathy, hereditary sensory and autonomic, type 1A	Uncertain significance (Jan 13, 2018)
9-92031163-A-C		Neuropathy, hereditary sensory and autonomic, type 1A	Benign (Jun 14, 2016)
9-92031239-C-A		Neuropathy, hereditary sensory and autonomic, type 1A	Likely benign (Jun 14, 2016)
9-92031295-A-G		Neuropathy, hereditary sensory and autonomic, type 1A	Benign (Jan 13, 2018)
9-92031311-A-G		Neuropathy, hereditary sensory and autonomic, type 1A	Benign (Jan 13, 2018)
9-92031372-C-T		Neuropathy, hereditary sensory and autonomic, type 1A	Uncertain significance (Jan 12, 2018)
9-92031456-C-A		Neuropathy, hereditary sensory and autonomic, type 1A	Benign (Jan 12, 2018)
9-92031668-A-C		Neuropathy, hereditary sensory and autonomic, type 1A	Uncertain significance (Jan 12, 2018)
9-92031715-G-A		Neuropathy, hereditary sensory and autonomic, type 1A	Uncertain significance (Jan 13, 2018)
9-92031834-C-G		Neuropathy, hereditary sensory and autonomic, type 1A	Uncertain significance (Jan 12, 2018)
9-92031860-A-G		Neuropathy, hereditary sensory and autonomic, type 1A	Uncertain significance (Jun 14, 2016)
9-92031962-G-A		Neuropathy, hereditary sensory and autonomic, type 1A	Uncertain significance (Jan 13, 2018)
9-92031975-T-C		Neuropathy, hereditary sensory and autonomic, type 1A	Benign (Jan 13, 2018)
9-92031982-T-C		Neuropathy, hereditary sensory and autonomic, type 1A	Benign (Jan 12, 2018)
9-92032014-C-A		Neuropathy, hereditary sensory and autonomic, type 1A	Uncertain significance (Jan 13, 2018)
9-92032014-C-T		Neuropathy, hereditary sensory and autonomic, type 1A	Uncertain significance (Jan 12, 2018)
9-92032020-T-C		Neuropathy, hereditary sensory and autonomic, type 1A	Likely benign (Jun 14, 2016)
9-92032265-C-A		Neuropathy, hereditary sensory and autonomic, type 1A	Uncertain significance (Jan 13, 2018)
9-92032275-T-G		Neuropathy, hereditary sensory and autonomic, type 1A	Benign (Jan 13, 2018)
9-92032287-A-T		Neuropathy, hereditary sensory and autonomic, type 1A	Benign (Jan 13, 2018)
9-92032341-T-C		Neuropathy, hereditary sensory and autonomic, type 1A	Benign/Likely benign (Nov 22, 2023)
9-92032465-C-G		Hereditary sensory and autonomic neuropathy type 1	Uncertain significance (Nov 28, 2023)
9-92032465-C-T		Hereditary sensory and autonomic neuropathy type 1	Uncertain significance (May 05, 2019)
9-92032476-C-T		Hereditary sensory and autonomic neuropathy type 1 • Charcot-Marie-Tooth disease • Neuropathy, hereditary sensory and autonomic, type 1A • not specified	Benign/Likely benign (Jan 28, 2024)
9-92032477-G-A		not specified • Hereditary sensory and autonomic neuropathy type 1 • Inborn genetic diseases	Benign/Likely benign (Nov 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPTLC1	protein_coding	protein_coding	ENST00000262554	15	83386

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.19e-11	0.779	125697	0	51	125748	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.13	208	259	0.803	0.0000141	3065
Missense in Polyphen		68	98.358	0.69135		1128
Synonymous	-0.300	97	93.3	1.04	0.00000509	914
Loss of Function	1.65	21	30.9	0.679	0.00000167	364

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000435	0.000427
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.000381	0.000381
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.000381	0.000381
South Asian	0.000229	0.000229
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine palmitoyltransferase (SPT). The heterodimer formed with SPTLC2 or SPTLC3 constitutes 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. {ECO:0000269|PubMed:19416851}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:11242114, ECO:0000269|PubMed:19132419, ECO:0000269|PubMed:19651702, ECO:0000269|PubMed:20504773, ECO:0000269|PubMed:21618344, ECO:0000269|PubMed:22302274, ECO:0000269|PubMed:24247255}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=SPTLC1 mutations at Ser-331 are responsible for severe hereditary motor and sensory neuropathy (HMSN) forms, whose core features are severe, diffuse muscle wasting and hypotonia, motor and sensory disturbances, foot ulcers, amputations and/or burns, joint hypermobility, cataracts and considerable growth retardation. {ECO:0000269|PubMed:23454272}.
• Pathway: Sphingolipid signaling pathway - Homo sapiens (human);Sphingolipid metabolism - Homo sapiens (human);Sphingolipid Metabolism;Gaucher Disease;Globoid Cell Leukodystrophy;Metachromatic Leukodystrophy (MLD);Fabry disease;Krabbe disease;Sphingolipid Metabolism;miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Metabolism of lipids;Metabolism;Glycosphingolipid metabolism;ceramide <i>de novo</i> biosynthesis;Sphingolipid de novo biosynthesis;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.225

Intolerance Scores

• loftool: 0.286
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.99

Haploinsufficiency Scores

• pHI: 0.380
• hipred: Y
• hipred_score: 0.596
• ghis: 0.606

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.965

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sptlc1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype

Gene ontology

• Biological process: sphingolipid metabolic process;sphingomyelin biosynthetic process;sphingolipid biosynthetic process;sphinganine biosynthetic process;sphingosine biosynthetic process;ceramide biosynthetic process;positive regulation of lipophagy
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;integral component of membrane;serine C-palmitoyltransferase complex;SPOTS complex
• Molecular function: serine C-palmitoyltransferase activity;protein binding;pyridoxal phosphate binding