CDK5R1

cyclin dependent kinase 5 regulatory subunit 1

Basic information

Region (hg38): 17:32486992-32491253

Links

ENSG00000176749 ∙ NCBI:8851 ∙ OMIM:603460 ∙ HGNC:1775 ∙ Uniprot:Q15078 ∙ 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 CDK5R1 gene.

• Inborn genetic diseases (5 variants)
• not provided (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDK5R1 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			6			6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	6	0	3

Variants in CDK5R1

This is a list of pathogenic ClinVar variants found in the CDK5R1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-32487661-C-T		not specified	Uncertain significance (Jan 03, 2024)
17-32487793-T-G		not specified	Uncertain significance (Jul 14, 2021)
17-32487800-CAAG-C		CDK5R1-related disorder	Benign (Feb 20, 2019)
17-32487810-A-G		not specified	Uncertain significance (Dec 14, 2023)
17-32487830-C-T			Benign (Apr 06, 2018)
17-32487850-A-C		not specified	Uncertain significance (Sep 30, 2021)
17-32488049-C-T			Benign (May 20, 2018)
17-32488111-A-T		not specified	Uncertain significance (Oct 04, 2022)
17-32488210-C-T		not specified	Uncertain significance (Feb 16, 2023)
17-32488243-G-T		not specified	Uncertain significance (Sep 29, 2023)
17-32488369-T-C			Uncertain significance (Sep 01, 2021)
17-32488418-C-T			Benign (Dec 13, 2018)
17-32488460-C-A		not specified	Uncertain significance (Dec 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDK5R1	protein_coding	protein_coding	ENST00000313401	1	4638

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.915	0.0846	125574	0	2	125576	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.91	115	189	0.608	0.0000124	1979
Missense in Polyphen		32	85.57	0.37396		903
Synonymous	-0.635	102	94.2	1.08	0.00000680	663
Loss of Function	2.61	0	7.92	0.00	3.48e-7	91

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000546	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.00000884	0.00000881
Middle Eastern	0.0000546	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: p35 is a neuron specific activator of CDK5. The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Activator of TPKII. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in association with altered stability and subcellular distribution. {ECO:0000269|PubMed:24235147}.
• Pathway: Alzheimer,s disease - Homo sapiens (human);Cocaine addiction - Homo sapiens (human);Alzheimers Disease;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;ATM Signaling Network in Development and Disease;Developmental Biology;Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer,s disease models;Neurodegenerative Diseases;Disease;Signal Transduction;Gene expression (Transcription);regulation of ck1/cdk5 by type 1 glutamate receptors;lissencephaly gene (lis1) in neuronal migration and development;deregulation of cdk5 in alzheimers disease;phosphorylation of mek1 by cdk5/p35 down regulates the map kinase pathway;rac1 cell motility signaling pathway;Generic Transcription Pathway;RNA Polymerase II Transcription;Activated NTRK2 signals through CDK5;Signaling by NTRK2 (TRKB);Signaling by NTRKs;Glucocorticoid receptor regulatory network;Semaphorin interactions;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Axon guidance;CRMPs in Sema3A signaling;Signaling by Receptor Tyrosine Kinases;Reelin signaling pathway;Trk receptor signaling mediated by the MAPK pathway;Lissencephaly gene (LIS1) in neuronal migration and development (Consensus)

Recessive Scores

• pRec: 0.184

Intolerance Scores

• loftool: 0.0469
• rvis_EVS: -0.14
• rvis_percentile_EVS: 42.88

Haploinsufficiency Scores

• pHI: 0.545
• hipred: Y
• hipred_score: 0.837
• ghis: 0.651

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.923

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cdk5r1
• Phenotype: cellular phenotype; homeostasis/metabolism 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); growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype

Zebrafish Information Network

• Gene name: cdk5r1a
• Affected structure: bile ductule
• Phenotype tag: abnormal
• Phenotype quality: decreased branchiness

Gene ontology

• Biological process: regulation of cyclin-dependent protein serine/threonine kinase activity;microtubule cytoskeleton organization;neuron migration;neuron cell-cell adhesion;G protein-coupled acetylcholine receptor signaling pathway;axon guidance;axonal fasciculation;brain development;cell population proliferation;embryo development ending in birth or egg hatching;regulation of macroautophagy;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;cerebellum development;superior olivary nucleus maturation;hippocampus development;layer formation in cerebral cortex;neuron differentiation;negative regulation of axon extension;positive regulation of microtubule polymerization;neuron projection development;regulation of actin cytoskeleton organization;ionotropic glutamate receptor signaling pathway;serine phosphorylation of STAT protein;positive regulation of neuron apoptotic process;regulation of neuron differentiation;negative regulation of transcription, DNA-templated;ephrin receptor signaling pathway;rhythmic process;regulation of dendritic spine morphogenesis;positive regulation of cell cycle arrest;positive regulation of protein serine/threonine kinase activity;positive regulation of protein targeting to membrane;regulation of synaptic vesicle cycle
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;microtubule;plasma membrane;postsynaptic density;membrane;protein kinase 5 complex;axon;dendrite;growth cone;neuromuscular junction;neuron projection;neuronal cell body;dendritic spine;intracellular membrane-bounded organelle;contractile fiber;perinuclear region of cytoplasm;presynapse
• Molecular function: protease binding;protein kinase activity;calcium ion binding;protein binding;kinase activity;protein kinase binding;ionotropic glutamate receptor binding;alpha-tubulin binding;protein serine/threonine kinase activator activity;cadherin binding;ephrin receptor binding;beta-tubulin binding;actin filament binding;cyclin-dependent protein serine/threonine kinase activator activity