CDKAL1 Gene
CDK5 Regulatory Subunit Associated Protein 1 Like 1
Gene Information Card
| Symbol | CDKAL1 |
|---|---|
| Full Name | CDK5 Regulatory Subunit Associated Protein 1 Like 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p22.3 |
| NCBI Gene ID | 54901 ncbi.nlm.nih.gov/gene/54901 |
| Ensembl ID | ENSG00000145996 |
| UniProt ID | Q5VV42 |
| OMIM ID | 611259 |
| HGNC ID | 25566 |
| Aliases | FLJ20315, MGC131981, MGC149532 |
Description
CDKAL1 encodes a methylthiotransferase enzyme that modifies mitochondrial tRNAs, specifically catalyzing the 2-methylthio-N6-isopentenyladenosine (ms2i6A37) modification. This modification is critical for accurate codon-anticodon pairing during translation. The gene is primarily expressed in pancreatic islets and skeletal muscle. Variants in CDKAL1 have been strongly associated with type 2 diabetes and impaired insulin secretion.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 2 Diabetes | Risk variants (e.g., rs7756992) reduce CDKAL1 expression in pancreatic beta cells, impairing insulin secretion via defective tRNA modification and translational fidelity. | GWAS (PMID: 17463246, 17463248); functional studies (PMID: 21706001) |
| Impaired Glucose Tolerance | Reduced CDKAL1 activity leads to defective proinsulin processing and decreased glucose-stimulated insulin secretion. | Functional studies in islets (PMID: 21706001) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 12.5 | Medium |
| Skeletal Muscle | 8.3 | Low |
| Liver | 4.1 | Low |
| Adipose Tissue | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| INS-1 (rat beta cell) | N/A | Model for insulin secretion studies |
| HeLa | N/A | Low expression; used in overexpression studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs7756992 | SNP (intronic) | ~30% in European populations | Associated with reduced CDKAL1 expression and increased type 2 diabetes risk |
| rs9465871 | SNP (intronic) | ~25% in East Asian populations | Associated with impaired insulin secretion |
Mutation functional classification
Loss of Function (LOF)
Reduced CDKAL1 expression or activity impairs tRNA modification, leading to defective translation of insulin and other beta-cell proteins.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
| • tRNA methylthiotransferase activity (GO:0035600) | • tRNA modification (GO:0006400) |
| • mitochondrion (GO:0005739) | • nucleus (GO:0005634) |
Pathways
• tRNA modification in mitochondria
• Insulin secretion pathway
Protein Summary
CDKAL1 is a 579-amino acid protein localized to mitochondria and the nucleus. It belongs to the methylthiotransferase family and contains a radical SAM domain. The protein catalyzes the conversion of N6-isopentenyladenosine (i6A37) to 2-methylthio-N6-isopentenyladenosine (ms2i6A37) in mitochondrial tRNAs, ensuring translational accuracy. Loss of function impairs insulin production.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CDKAL1 Knockout HEK293 Cell Line | EDJ-KQ12845 | Human | 54901 | Details Get a Quote |
| CDKAL1 Knockout HCT 116 Cell Line | EDJ-KQ41999 | Human | 54901 | Details Get a Quote |
| CDKAL1 Knockout HeLa Cell Line | EDJ-KQ42000 | Human | 54901 | Details Get a Quote |
| CDKAL1 Knockout A-549 Cell Line | EDJ-KQ40749 | Human | 54901 | Details Get a Quote |
