CERS1

Chr 19AR

ceramide synthase 1

Also known as: EPM8, LAG1, LASS1, UOG1

NCBI Gene: 10715ENSG00000223802UniProt: P27544

This gene encodes a ceramide synthase enzyme, which catalyzes the synthesis of ceramide, the hydrophobic moiety of sphingolipids. The encoded enzyme synthesizes 18-carbon (C18) ceramide in brain neurons. Elevated expression of this gene may be associated with increased longevity, while decreased expression of this gene may be associated with myoclonus epilepsy with dementia in human patients. This protein is transcribed from a monocistronic mRNA as well as a bicistronic mRNA, which also encodes growth differentiation factor 1. [provided by RefSeq, Jul 2016]

Primary Disease Associations & Inheritance

Epilepsy, progressive myoclonic, 8MIM #616230
AR
587
ClinVar variants
30
Pathogenic / LP
0.10
pLI score
0
Active trials
Clinical Summary— CERS1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
30 Pathogenic / Likely Pathogenic· 233 VUS of 587 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.69LOEUF
pLI 0.097
Z-score 2.35
OE 0.30 (0.15–0.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.82Z-score
OE missense 0.82 (0.71–0.95)
137 obs / 166.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.30 (0.15–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.71–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03
0≤1.21.6
LoF obs/exp: 4 / 13.2Missense obs/exp: 137 / 166.6Syn Z: -0.19

ClinVar Variant Classifications

587 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic15
VUS233
Likely Benign201
Benign14
Conflicting8
15
Pathogenic
15
Likely Pathogenic
233
VUS
201
Likely Benign
14
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
9
0
15
Likely Pathogenic
8
5
2
0
15
VUS
6
208
16
3
233
Likely Benign
0
4
50
147
201
Benign
0
1
9
4
14
Conflicting
—8
Total1921986154486

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

View in ClinVar →

Protein Context — Lollipop Plot

CERS1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Epilepsy, progressive myoclonic, 8

MIM #616230

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CERS1 is a biomarker of Staphylococcus aureus abundance and atopic dermatitis severity.
Kenney HM et al.·J Allergy Clin Immunol
2025Clinical trial
Concerted functions of HDAC1 and microRNA-574-5p repress alternatively spliced ceramide synthase 1 expression in human cancer cells.
Meyers-Needham M et al.·EMBO Mol Med
2012
Spinal muscular atrophy associated with progressive myoclonus epilepsy.
Topaloglu H et al.·Epileptic Disord
2016Review
Whole-transcriptome sequencing of phagocytes reveals a ceRNA network contributing to natural resistance to tuberculosis infection.
Ran F et al.·Microb Pathog
2024
Inhibitors of specific ceramide synthases.
Schiffmann S et al.·Biochimie
2012
CLN5 and CLN8 protein association with ceramide synthase: biochemical and proteomic approaches.
Haddad SE et al.·Electrophoresis
2012
(Dihydro)ceramide synthase 1 regulated sensitivity to cisplatin is associated with the activation of p38 mitogen-activated protein kinase and is abrogated by sphingosine kinase 1.
Min J et al.·Mol Cancer Res
2007
Progressive myoclonus epilepsies-Residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes.
Courage C et al.·Am J Hum Genet
2021Cohort
Decreased ceramide underlies mitochondrial dysfunction in Charcot-Marie-Tooth 2F.
Schwartz NU et al.·FASEB J
2018
A fluorescent assay for ceramide synthase activity.
Kim HJ et al.·J Lipid Res
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools