CLYBL: Citrate Lyase Beta-Like Gene
A mitochondrial enzyme involved in vitamin B12 metabolism and associated with rare metabolic disorders
Gene Information Card
| Symbol | CLYBL |
|---|---|
| Full Name | Citrate Lyase Beta-Like |
| Gene Type | Protein-coding |
| Chromosomal Location | 13q32.3 |
| NCBI Gene ID | 171425 ncbi.nlm.nih.gov/gene/171425 |
| Ensembl ID | ENSG00000139618 |
| UniProt ID | Q8N0W4 |
| OMIM ID | 614462 |
| HGNC ID | 26887 |
| Aliases | CLYBL1, MGC13170 |
Description
CLYBL encodes a mitochondrial enzyme that belongs to the citrate lyase beta-like family. It is involved in the metabolism of vitamin B12 (cobalamin) by converting malonyl-CoA to acetyl-CoA and CO2, a key step in the mitochondrial processing of B12. Loss-of-function mutations in CLYBL cause a rare autosomal recessive disorder characterized by vitamin B12 deficiency, methylmalonic aciduria, and neurological symptoms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| CLYBL deficiency (vitamin B12-responsive methylmalonic aciduria) | Loss-of-function mutations impair mitochondrial B12 metabolism, leading to accumulation of methylmalonic acid and reduced B12 cofactor availability | PMID: 28135719, ClinVar |
| Methylmalonic aciduria with homocystinuria (cblX type) | Defective CLYBL disrupts cobalamin processing, causing combined methylmalonic aciduria and homocystinuria | PMID: 28135719, OMIM #614462 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.3 | Medium |
| Heart | 8.1 | Medium |
| Brain | 3.2 | Low |
| Skeletal Muscle | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.0 | Hepatocellular carcinoma cell line |
| HEK293 | 9.5 | Embryonic kidney cells |
| K562 | 6.8 | Leukemia cell line |
| HeLa | 4.2 | Cervical cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.359G>A (p.Arg120His) | Missense | Rare (MAF <0.01%) | Loss of enzyme activity; associated with CLYBL deficiency |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein expression |
| c.844C>T (p.Arg282*) | Nonsense | Rare | Premature stop; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most reported CLYBL mutations are loss-of-function, leading to reduced or absent enzyme activity and impaired vitamin B12 metabolism.
Gain of Function (GOF)
No gain-of-function mutations have been reported for CLYBL.
Dominant Negative (DN)
No dominant-negative mutations have been described for CLYBL.
View complete mutation data：
Gene Ontology (GO)
| • mitochondrion (GO:0005739) | • citrate (pro-3S)-lyase activity (GO:0003983) |
| • fatty acid biosynthetic process (GO:0006633) | • cobalamin metabolic process (GO:0009235) |
| • cytosol (GO:0005829) |
Pathways
• Vitamin B12 (cobalamin) metabolism
• Propanoate metabolism
• Fatty acid biosynthesis
Protein Summary
CLYBL is a 45 kDa mitochondrial protein that functions as a citrate lyase beta-like enzyme. It catalyzes the conversion of malonyl-CoA to acetyl-CoA and CO2, a reaction essential for the mitochondrial processing of vitamin B12. The protein is expressed predominantly in liver and kidney, tissues with high metabolic demand for B12. Structural studies indicate a homodimeric organization with a conserved CoA-binding domain.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLYBL Knockout HEK293 Cell Line | EDJ-KQ12956 | Human | 171425 | Details Get a Quote |
| CLYBL Knockout HeLa Cell Line | EDJ-KQ40921 | Human | 171425 | Details Get a Quote |
| CLYBL Knockout A-549 Cell Line | EDJ-KQ42163 | Human | 171425 | Details Get a Quote |
| CLYBL Knockout HCT 116 Cell Line | EDJ-KQ42164 | Human | 171425 | Details Get a Quote |
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