CLYBL
Chr 13citramalyl-CoA lyase
Also known as: CLB
This mitochondrial enzyme detoxifies vitamin B12-poisoning metabolites by acting as a citramalyl-CoA lyase to convert citramalyl-CoA into acetyl-CoA and pyruvate, and functions as a malyl-CoA thioesterase to detoxify toxic malyl-CoA that interferes with vitamin B12-dependent metabolism. Mutations cause autosomal recessive malonic aciduria with developmental delay, seizures, and metabolic decompensation typically presenting in early childhood. The gene shows relaxed evolutionary constraint, suggesting tolerance to some loss-of-function variation.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
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.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
171 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 94 | 0 | 94 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 59 | 4 | 0 | 63 |
Likely Benign | 0 | 1 | 2 | 0 | 3 |
Benign | 0 | 0 | 0 | 0 | 0 |
| Total | 0 | 60 | 102 | 0 | 162 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CLYBL · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools