SPTLC2

Chr 14AD

serine palmitoyltransferase long chain base subunit 2

Also known as: HSN1C, LCB2, LCB2A, NSAN1C, SPT2, hLCB2a

NCBI Gene: 9517 ENSG00000100596 UniProt: O15270 OMIM: 605713

The SPTLC2 protein forms the catalytic core of serine palmitoyltransferase, the rate-limiting enzyme in sphingolipid biosynthesis that condenses L-serine with palmitoyl-CoA to generate long-chain bases. Mutations cause hereditary sensory and autonomic neuropathy type IC, an autosomal dominant peripheral neuropathy affecting sensory and autonomic nerve function. This gene is highly constrained against loss-of-function variants (LOEUF 0.39), indicating intolerance to protein-disrupting mutations.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a long chain base subunit of serine palmitoyltransferase. Serine palmitoyltransferase, which consists of two different subunits, is the key enzyme in sphingolipid biosynthesis. It catalyzes the pyridoxal-5-prime-phosphate-dependent condensation of L-serine and palmitoyl-CoA to 3-oxosphinganine. Mutations in this gene were identified in patients with hereditary sensory neuropathy type I. [provided by RefSeq, Mar 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

ADLOEUF 0.391 OMIM phenotype

Clinical Summary— SPTLC2

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Gene-Disease Validity (ClinGen)

neuropathy, hereditary sensory and autonomic, type 1C · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.78) — some intolerance to loss-of-function variants.

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ClinVar Variants

11 unique Pathogenic / Likely Pathogenic· 345 VUS of 708 total submissions

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GeneReview available — SPTLC2

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.39LOEUF

pLI 0.780

Z-score 3.92

OE 0.19 (0.10–0.39)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.04Z-score

OE missense 0.68 (0.60–0.76)

210 obs / 311.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.19 (0.10–0.39)

0≤0.351.4

Missense OE?0.68 (0.60–0.76)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 5 / 27.0Missense obs/exp: 210 / 311.0Syn Z: -0.63

ClinVar Variant Classifications

708 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic5

VUS345

Likely Benign201

Benign114

Conflicting20

Pathogenic

Likely Pathogenic

345

VUS

201

Likely Benign

114

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	5	1	0	6
Likely Pathogenic	0	5	0	0	5
VUS	15	232	96	2	345
Likely Benign	0	14	68	119	201
Benign	0	2	107	5	114
Conflicting	—				20
Total	15	258	272	126	691

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

15 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap SPTLC2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →