CDKAL1

CDK5 regulatory subunit associated protein 1 like 1, the group of Radical S-adenosylmethionine domain containing

Basic information

Region (hg38): 6:20534456-21232404

Links

ENSG00000145996 ∙ NCBI:54901 ∙ OMIM:611259 ∙ HGNC:21050 ∙ Uniprot:Q5VV42 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDKAL1 gene.

• Inborn genetic diseases (16 variants)
• not provided (7 variants)
• Type 2 diabetes mellitus (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDKAL1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					3	3
missense			16	2		18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)				1		1
splice region					1	1
non coding						0
Total	0	0	16	3	3

Variants in CDKAL1

This is a list of pathogenic ClinVar variants found in the CDKAL1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-20546446-G-C		not specified	Uncertain significance (Jan 26, 2022)
6-20546466-G-A			Likely benign (Dec 31, 2019)
6-20546472-G-A		not specified	Uncertain significance (Dec 08, 2023)
6-20548633-G-T		not specified	Uncertain significance (Oct 25, 2022)
6-20548646-A-G		not specified	Uncertain significance (Nov 17, 2022)
6-20649303-C-T			Benign (Mar 30, 2018)
6-20660803-A-C		Type 2 diabetes mellitus	Uncertain significance (Sep 01, 2014)
6-20661019-G-C		Obesity	risk factor (Dec 26, 2019)
6-20679478-A-G		Type 2 diabetes mellitus	Uncertain significance (Sep 01, 2014)
6-20739524-C-T		not specified	Uncertain significance (Jan 22, 2024)
6-20739529-G-A		not specified	Uncertain significance (Jan 06, 2023)
6-20739581-G-A		not specified	Uncertain significance (Sep 30, 2022)
6-20739602-T-A		not specified	Uncertain significance (Mar 07, 2023)
6-20758610-C-A		not specified	Uncertain significance (Oct 05, 2022)
6-20781190-G-A		not specified	Uncertain significance (Nov 02, 2023)
6-20781218-G-A			Benign (Dec 11, 2017)
6-20781222-A-G		not specified	Uncertain significance (Jul 25, 2023)
6-20846140-T-C		not specified	Uncertain significance (Feb 12, 2024)
6-20955443-C-A		not specified	Uncertain significance (Nov 10, 2022)
6-20955494-C-T		not specified	Uncertain significance (Oct 06, 2021)
6-21065095-G-A		not specified	Uncertain significance (Jan 31, 2022)
6-21065193-C-T		not specified	Uncertain significance (Aug 29, 2022)
6-21108400-GA-G		Type 2 diabetes mellitus	not provided (-)
6-21198076-A-T			Likely benign (Dec 17, 2018)
6-21201136-C-A		not specified	Uncertain significance (Aug 23, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDKAL1	protein_coding	protein_coding	ENST00000274695	14	697948

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0160	0.984	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.66	229	311	0.735	0.0000157	3809
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000304	0.000303
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000972	0.0000967
Middle Eastern	0.000109	0.000109
South Asian	0.000168	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Vitamin D Receptor Pathway (Consensus)

Recessive Scores

• pRec: 0.247

Intolerance Scores

• loftool: 0.585
• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.72

Haploinsufficiency Scores

• pHI: 0.234
• hipred: N
• hipred_score: 0.488
• ghis: 0.594

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.305

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cdkal1
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; hematopoietic system phenotype; normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; immune system phenotype; vision/eye phenotype

Zebrafish Information Network

• Gene name: cdkal1
• Affected structure: pancreatic B cell
• Phenotype tag: abnormal
• Phenotype quality: decreased area

Gene ontology

• Biological process: tRNA modification;biological_process;tRNA methylthiolation;maintenance of translational fidelity
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;rough endoplasmic reticulum;membrane;integral component of membrane
• Molecular function: molecular_function;protein binding;N6-threonylcarbomyladenosine methylthiotransferase activity;metal ion binding;4 iron, 4 sulfur cluster binding;tRNA (N(6)-L-threonylcarbamoyladenosine(37)-C(2))-methylthiotransferase