CERT1

Chr 5AD

ceramide transporter 1

NCBI Gene: 10087ENSG00000113163UniProt: Q9Y5P4

Shelters ceramides inside its steroidogenic acute regulatory lipid transfer (START) domain and mediates their intracellular trafficking in a non-vesicular manner from the endoplasmic reticulum to the Golgi apparatus for conversion to sphingomyelin (PubMed:14685229, PubMed:15596449, PubMed:17591919, PubMed:18184806, PubMed:20036255). Efficiently transfers ceramide molecules having long-chain fatty chains, but not those with very long acyl chains (PubMed:15596449, PubMed:18184806). Capable of transferring diacylglycerol, although with very low efficiency (PubMed:18184806)

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hypotonia, speech delay, and dysmorphic faciesMIM #616351
AD
266
ClinVar variants
23
Pathogenic / LP
0.67
pLI score
1
Active trials
Clinical Summary— CERT1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.67) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 159 VUS of 266 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

pubmed: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.36LOEUF
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?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.
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?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.0.21 (0.13–0.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.61–0.74)
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.1.19
0≤1.21.6
LoF obs/exp: 9 / 43.1Missense obs/exp: 272 / 405.9Syn Z: -1.79

ClinVar Variant Classifications

266 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic9
VUS159
Likely Benign71
Benign7
Conflicting6
14
Pathogenic
9
Likely Pathogenic
159
VUS
71
Likely Benign
7
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
12
0
14
Likely Pathogenic
0
8
1
0
9
VUS
7
138
11
3
159
Likely Benign
1
25
15
30
71
Benign
0
2
3
2
7
Conflicting
—6
Total81754235266

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

View 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.

Gene2Phenotype Curations

CERT1-related intellectual disability

definitive
ADGain Of FunctionAltered Gene Product Structure
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with hypotonia, speech delay, and dysmorphic facies

MIM #616351

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
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
Lifestyle FactorsOverweight and ObesityInsulin Sensitivity

Effect of Sleep Extension on Ceramides in People with Overweight and Obesity

RECRUITING
NCT06180837Phase NAUniversity of UtahStarted 2024-02-12
Sleep Extension Intervention

External Resources

Links to major genomics databases and tools