CLYBL
protein-codingcitramalyl-CoA lyase, the group of MicroRNA protein coding host genes
Gene summary
Enables several functions, including (S)-citramalyl-CoA lyase activity; magnesium ion binding activity; and malate synthase activity. Involved in protein homotrimerization; regulation of cobalamin metabolic process; and toxic metabolite repair. Is active in mitochondrion. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~302.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CLYBL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_206808.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 60 | 1 | 61 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 64 | 1 | 0 | 65 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_996531.1 | 8 | MANE Select | |
| Ensembl | ENSP00000342991.4 | 8 | MANE Select | |
| RefSeq | NP_001380284.1 | 7 | Standard | |
| RefSeq | NP_001380285.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TCA cycle
Biological Process
- protein homotrimerization
- regulation of cobalamin metabolic process
Molecular Function
- magnesium ion binding
- malate synthase activity
- (3S)-citramalyl-CoA lyase activity
Cellular Component
- mitochondrion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000376360
- Coding exons
- 8
- Length
- 290469
- Individuals with no LoFs
- 118661
- Homozygous LoFs
- 121
- Heterozygous LoFs
- 6966
- Defined
- 125748
- p
- 0.0286
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0788 | 183 | 180 | 1.02 | 0.00000947 | 2181 |
| Missense (PolyPhen) | 61 | 61.305 | 0.99503 | 723 | ||
| Synonymous | -0.833 | 80 | 71.1 | 1.13 | 0.00000396 | 701 |
| Loss of Function | 0.582 | 15 | 17.6 | 0.850 | 0.00000102 | 198 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0065 | 0.0064 | notable |
| Latino/Admixed American | 0.026 | 0.026 | notable |
| Ashkenazi Jewish | 0.050 | 0.050 | notable |
| East Asian | 0.050 | 0.050 | notable |
| Finnish | 0.036 | 0.036 | notable |
| European (Non-Finnish) | 0.027 | 0.027 | notable |
| South Asian | 0.024 | 0.023 | notable |
| Other | 0.034 | 0.034 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Mitochondrial citramalyl-CoA lyase indirectly involved in the vitamin B12 metabolism (PubMed:29056341). Converts citramalyl-CoA into acetyl-CoA and pyruvate in the C5- dicarboxylate catabolism pathway (PubMed:29056341). The C5- dicarboxylate catabolism pathway is required to detoxify itaconate, a vitamin B12-poisoning metabolite (PubMed:29056341). Also acts as a malate synthase in vitro, converting glyoxylate and acetyl-CoA to malate (PubMed:24334609, PubMed:29056341). Also acts as a beta-methylmalate synthase in vitro, by mediating conversion of glyoxylate and propionyl-CoA to beta-methylmalate (PubMed:24334609, PubMed:29056341). Also has very weak citramalate synthase activity in vitro (PubMed:24334609, PubMed:29056341). {ECO:0000269|PubMed:24334609, ECO:0000269|PubMed:29056341}.;
Recessive Scores
- pRec
- 0.323
Intolerance Scores
- LoFtool
- 0.889
- RVIS EVS
- 0.77
- RVIS percentile EVS
- 87.06
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.848
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |