SPTLC2

Chr 14AD

serine palmitoyltransferase long chain base subunit 2

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

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ADLOEUF 0.391 OMIM phenotype
Clinical SummarySPTLC2
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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

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.78) — some intolerance to loss-of-function variants.
📖
GeneReview available — SPTLC2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.780
Z-score 3.92
OE 0.19 (0.100.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.04Z-score
OE missense 0.68 (0.600.76)
210 obs / 311.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.19 (0.100.39)
00.351.4
Missense OE0.68 (0.600.76)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 5 / 27.0Missense obs/exp: 210 / 311.0Syn Z: -0.63

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SPTLC2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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