CERT1

Chr 5AD

ceramide transporter 1

Also known as: CERT, CERTL, COL4A3BP, GPBP, MRD34, NEDHSF, STARD11

NCBI Gene: 10087 ENSG00000113163 UniProt: Q9Y5P4 OMIM: 604677

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.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a kinase that specifically phosphorylates the N-terminal region of the non-collagenous domain of the alpha 3 chain of type IV collagen, known as the Goodpasture antigen. Goodpasture disease is the result of an autoimmune response directed at this antigen. One isoform of this protein is also involved in ceramide intracellular transport. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

GOFmechanismADLOEUF 0.361 OMIM phenotype

Clinical Summary— CERT1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.67) — some intolerance to loss-of-function variants.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.36LOEUF

pLI 0.667

Z-score 4.81

OE 0.21 (0.13–0.36)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.36Z-score

OE missense 0.67 (0.61–0.74)

272 obs / 405.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.21 (0.13–0.36)

0≤0.351.4

Missense OE?0.67 (0.61–0.74)

0≤0.61.4

Synonymous OE?1.19

0≤1.21.6

LoF obs/exp: 9 / 43.1Missense obs/exp: 272 / 405.9Syn Z: -1.79

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCERT1-related intellectual disabilityGOFAD

This gene — mechanism propensity

0.6358th %ile

GOF

0.6442th %ile

LOF

0.4135th %ile

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.

GOFprediction above median · 1 literature citation

DNprediction above median

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

GOFIntellectual disability-associated gain-of-function mutations in CERT1 that encodes the ceramide transport protein CERT.1

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

References