CERS3

Chr 15AR

ceramide synthase 3

Also known as: ARCI9, LASS3

This protein functions as a ceramide synthase that catalyzes the formation of ultra-long-chain ceramides from sphingoid bases and acyl-CoA substrates, which are essential for maintaining epidermal lipid homeostasis and the skin's protective barrier function. Mutations cause autosomal recessive congenital ichthyosis, characterized by epidermal defects due to impaired skin barrier formation. The gene shows low constraint against loss-of-function variants (pLI 0.006), consistent with its recessive inheritance pattern where heterozygous carriers are typically unaffected.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.631 OMIM phenotype
Clinical SummaryCERS3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.
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GeneReview available — CERS3
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.63LOEUF
pLI 0.006
Z-score 2.90
OE 0.35 (0.200.63)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.61Z-score
OE missense 0.88 (0.780.99)
183 obs / 207.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.35 (0.200.63)
00.351.4
Missense OE0.88 (0.780.99)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 8 / 23.0Missense obs/exp: 183 / 207.9Syn Z: -0.40
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCERS3-related ichthyosis, congenitalOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.79top 25%
GOF
0.6638th %ile
LOF
0.1993th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CERS3 · 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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