CERT1
Chr 5ADceramide transporter 1
Also known as: CERT, CERTL, COL4A3BP, GPBP, MRD34, NEDHSF, STARD11
The protein mediates intracellular trafficking of ceramides from the endoplasmic reticulum to the Golgi apparatus for sphingomyelin synthesis, sheltering ceramides within its START domain. Mutations cause autosomal dominant neurodevelopmental disorder with hypotonia, speech delay, and dysmorphic facies. The gene shows high constraint against loss-of-function variants (LOEUF 0.364), indicating intolerance to protein-disrupting mutations.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
CERT1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools