SPTLC2

serine palmitoyltransferase long chain base subunit 2

Basic information

Region (hg38): 14:77505997-77616637

Links

ENSG00000100596 ∙ NCBI:9517 ∙ OMIM:605713 ∙ HGNC:11278 ∙ Uniprot:O15270 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neuropathy, hereditary sensory and autonomic, type 1C (Strong), mode of inheritance: AD
• hereditary sensory and autonomic neuropathy type 1 (Supportive), mode of inheritance: AD
• neuropathy, hereditary sensory and autonomic, type 1C (Strong), mode of inheritance: AD
• neuropathy, hereditary sensory and autonomic, type 1C (Strong), mode of inheritance: AD
• neuropathy, hereditary sensory and autonomic, type 1C (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
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	20920666; 23658386; 26681808; 30626650; 30866134; 30955194

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPTLC2 gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPTLC2 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				93	5	98
missense	1	4	198	8	2	213
nonsense			5			5
start loss						0
frameshift			5			5
inframe indel			3	1		4
splice donor/acceptor (+/-2bp)			1			1
splice region			16	12	1	29
non coding			72	48	107	227
Total	1	4	284	150	114

Variants in SPTLC2

This is a list of pathogenic ClinVar variants found in the SPTLC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
14-77506031-A-G		Neuropathy, hereditary sensory and autonomic, type 1C	Benign (Jan 13, 2018)
14-77506115-C-A		Neuropathy, hereditary sensory and autonomic, type 1C	Uncertain significance (Jan 13, 2018)
14-77506204-G-C		Neuropathy, hereditary sensory and autonomic, type 1C	Benign (Jan 12, 2018)
14-77506216-G-A		Neuropathy, hereditary sensory and autonomic, type 1C	Uncertain significance (Jan 12, 2018)
14-77506266-T-G		Neuropathy, hereditary sensory and autonomic, type 1C	Uncertain significance (Jan 13, 2018)
14-77506294-A-AT		Neuropathy, hereditary sensory and autonomic, type 1C	Likely benign (Jun 14, 2016)
14-77506369-A-G		Neuropathy, hereditary sensory and autonomic, type 1C	Uncertain significance (Jan 13, 2018)
14-77506392-G-T		Neuropathy, hereditary sensory and autonomic, type 1C	Benign (Jan 13, 2018)
14-77506432-T-C		Neuropathy, hereditary sensory and autonomic, type 1C	Uncertain significance (Jan 12, 2018)
14-77506485-G-A		Neuropathy, hereditary sensory and autonomic, type 1C	Benign (Jan 13, 2018)
14-77506753-T-C		Neuropathy, hereditary sensory and autonomic, type 1C	Benign (Jan 13, 2018)
14-77506774-G-A		Neuropathy, hereditary sensory and autonomic, type 1C	Uncertain significance (Jan 13, 2018)
14-77506889-G-C		Neuropathy, hereditary sensory and autonomic, type 1C	Benign (Jan 13, 2018)
14-77506926-A-G		Neuropathy, hereditary sensory and autonomic, type 1C	Benign (Jan 13, 2018)
14-77506927-T-C		Neuropathy, hereditary sensory and autonomic, type 1C	Conflicting classifications of pathogenicity (Aug 01, 2022)
14-77506981-T-C		Neuropathy, hereditary sensory and autonomic, type 1C	Uncertain significance (Jan 13, 2018)
14-77507252-A-T		Neuropathy, hereditary sensory and autonomic, type 1C	Uncertain significance (Jan 12, 2018)
14-77507276-C-T		Neuropathy, hereditary sensory and autonomic, type 1C	Uncertain significance (Jan 12, 2018)
14-77507334-T-A		Neuropathy, hereditary sensory and autonomic, type 1C	Uncertain significance (Jan 13, 2018)
14-77507336-T-G		Neuropathy, hereditary sensory and autonomic, type 1C	Uncertain significance (Jan 12, 2018)
14-77507370-G-A		Neuropathy, hereditary sensory and autonomic, type 1C	Benign (Jan 13, 2018)
14-77507442-T-G		Neuropathy, hereditary sensory and autonomic, type 1C	Benign (Mar 06, 2018)
14-77507459-G-A		Neuropathy, hereditary sensory and autonomic, type 1C	Uncertain significance (Jan 12, 2018)
14-77507529-G-A		Neuropathy, hereditary sensory and autonomic, type 1C	Uncertain significance (Jan 13, 2018)
14-77507602-G-T		Neuropathy, hereditary sensory and autonomic, type 1C	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPTLC2	protein_coding	protein_coding	ENST00000216484	12	110777

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.780	0.220	125739	0	8	125747	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.04	210	311	0.675	0.0000172	3642
Missense in Polyphen		31	76.851	0.40338		908
Synonymous	-0.632	123	114	1.08	0.00000633	1110
Loss of Function	3.92	5	27.0	0.185	0.00000141	353

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000528	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine palmitoyltransferase (SPT). The heterodimer formed with LCB1/SPTLC1 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-SPTLC2-SPTSSB complex displays a preference for C18-CoA substrate. {ECO:0000269|PubMed:19416851, ECO:0000269|PubMed:20920666}.
• 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;Metabolism of lipids;Metabolism;Glycosphingolipid metabolism;ceramide <i>de novo</i> biosynthesis;Sphingolipid de novo biosynthesis;Sphingolipid metabolism (Consensus)

Recessive Scores

• pRec: 0.200

Intolerance Scores

• loftool: 0.0980
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.99

Haploinsufficiency Scores

• pHI: 0.264
• hipred: Y
• hipred_score: 0.749
• ghis: 0.500

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sptlc2
• 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); hematopoietic system phenotype; liver/biliary system phenotype; immune system phenotype; digestive/alimentary phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

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