CDKAL1
protein-codingCDK5 regulatory subunit associated protein 1 like 1, the group of Radical S-adenosylmethionine domain containing
Gene summary
The protein encoded by this gene is a member of the methylthiotransferase family. The function of this gene is not known. Genome-wide association studies have linked single nucleotide polymorphisms in an intron of this gene with susceptibilty to type 2 diabetes. [provided by RefSeq, May 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~697.9 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 CDKAL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017774.3. 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 | 1 | 3 | 4 | |||
| missense | 66 | 4 | 70 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 73 | 4 | 3 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060244.2 | 14 | MANE Select | |
| Ensembl | ENSP00000274695.4 | 14 | MANE Select | |
| Ensembl | ENSP00000367873.1 | 14 | Standard | |
| Ensembl | ENSP00000367873.1 | 14 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| cdkal1 | Danio rerio | Structure: pancreatic B cell Quality: decreased area abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- Vitamin D Receptor Pathway
Biological Process
- tRNA modification
- biological_process
- tRNA methylthiolation
- maintenance of translational fidelity
Molecular Function
- molecular_function
- protein binding
- N6-threonylcarbomyladenosine methylthiotransferase activity
- metal ion binding
- 4 iron, 4 sulfur cluster binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- rough endoplasmic reticulum
- membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000274695
- Coding exons
- 14
- Length
- 697948
- Individuals with no LoFs
- 125723
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 25
- Defined
- 125748
- p
- 0.0000994
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.66 | 229 | 311 | 0.735 | 0.0000157 | 3809 |
| Missense (PolyPhen) | 61 | 119.35 | 0.51109 | 1477 | ||
| Synonymous | -0.536 | 122 | 115 | 1.06 | 0.00000642 | 1093 |
| Loss of Function | 3.58 | 9 | 30.2 | 0.298 | 0.00000156 | 362 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000097 | 0.000097 | rare |
| South Asian | 0.00017 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the methylthiolation of N6- threonylcarbamoyladenosine (t(6)A), leading to the formation of 2- methylthio-N6-threonylcarbamoyladenosine (ms(2)t(6)A) at position 37 in tRNAs that read codons beginning with adenine. {ECO:0000269|PubMed:20584901}.;
Recessive Scores
- pRec
- 0.247
Intolerance Scores
- LoFtool
- 0.585
- RVIS EVS
- -0.58
- RVIS percentile EVS
- 18.72
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.305
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |