CDK6

cyclin dependent kinase 6, the group of Cyclin dependent kinases

Basic information

Region (hg38): 7:92604920-92836573

Links

ENSG00000105810 ∙ NCBI:1021 ∙ OMIM:603368 ∙ HGNC:1777 ∙ Uniprot:Q00534 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR
• microcephaly 12, primary, autosomal recessive (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly 12, primary, autosomal recessive	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	23918663

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CDK6 gene.

• not provided (26 variants)
• not specified (6 variants)
• Inborn genetic diseases (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDK6 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				10	2	12
missense			6		1	7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					12	12
Total	0	0	6	10	15

Variants in CDK6

This is a list of pathogenic ClinVar variants found in the CDK6 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-92609830-A-G		Behcet disease	association (Nov 14, 2021)
7-92615108-C-T			Benign (Jun 18, 2021)
7-92615172-T-A		not specified • CDK6-related disorder	Benign/Likely benign (Dec 31, 2019)
7-92615176-C-T			Likely benign (Oct 01, 2022)
7-92615227-T-C		not specified	Likely benign (Sep 29, 2016)
7-92615275-T-C		not specified	Likely benign (Dec 31, 2019)
7-92615316-TATACA-T			Benign (Jun 18, 2021)
7-92617798-C-T			Benign (Jun 18, 2021)
7-92618019-A-G			Benign (Jun 18, 2021)
7-92618131-C-T		not specified	Uncertain significance (Dec 11, 2015)
7-92618192-T-G			Likely benign (Sep 07, 2018)
7-92618206-C-T		not specified	Uncertain significance (Aug 02, 2021)
7-92618225-A-G			Benign (Jun 18, 2021)
7-92622889-C-G			Benign (Jun 18, 2021)
7-92623037-C-T		not specified	Uncertain significance (Apr 18, 2023)
7-92623075-C-T		not specified	Uncertain significance (Apr 13, 2023)
7-92623083-A-G			Benign (Apr 10, 2018)
7-92650049-T-C		Behcet disease	association (Nov 14, 2021)
7-92671273-G-A			Benign (Jun 18, 2021)
7-92671476-G-A			Likely benign (Apr 25, 2018)
7-92671484-C-T		Microcephaly 12, primary, autosomal recessive	Pathogenic (Dec 20, 2013)
7-92671485-G-A			Likely benign (Dec 31, 2019)
7-92671509-G-C			Likely benign (Jul 10, 2018)
7-92671527-C-T		not specified	Likely benign (Dec 31, 2019)
7-92671549-C-T			Benign (Jun 19, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CDK6	protein_coding	protein_coding	ENST00000265734	7	231674

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.983	0.0169	125531	0	1	125532	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.06	70	188	0.372	0.00000987	2108
Missense in Polyphen		24	82.482	0.29097		938
Synonymous	0.537	70	75.9	0.922	0.00000426	649
Loss of Function	3.58	1	16.8	0.0594	9.84e-7	184

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition. Phosphorylates pRB/RB1 and NPM1. Interacts with D-type G1 cyclins during interphase at G1 to form a pRB/RB1 kinase and controls the entrance into the cell cycle. Involved in initiation and maintenance of cell cycle exit during cell differentiation; prevents cell proliferation and regulates negatively cell differentiation, but is required for the proliferation of specific cell types (e.g. erythroid and hematopoietic cells). Essential for cell proliferation within the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. Required during thymocyte development. Promotes the production of newborn neurons, probably by modulating G1 length. Promotes, at least in astrocytes, changes in patterns of gene expression, changes in the actin cytoskeleton including loss of stress fibers, and enhanced motility during cell differentiation. Prevents myeloid differentiation by interfering with RUNX1 and reducing its transcription transactivation activity, but promotes proliferation of normal myeloid progenitors. Delays senescence. Promotes the proliferation of beta-cells in pancreatic islets of Langerhans. May play a role in the centrosome organization during the cell cycle phases (PubMed:23918663). {ECO:0000269|PubMed:12833137, ECO:0000269|PubMed:14985467, ECO:0000269|PubMed:15254224, ECO:0000269|PubMed:15809340, ECO:0000269|PubMed:17420273, ECO:0000269|PubMed:17431401, ECO:0000269|PubMed:20333249, ECO:0000269|PubMed:20668294, ECO:0000269|PubMed:23918663, ECO:0000269|PubMed:8114739}.
• Disease: DISEASE: Microcephaly 12, primary, autosomal recessive (MCPH12) [MIM:616080]: A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age- related mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. {ECO:0000269|PubMed:23918663}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Non-small cell lung cancer - Homo sapiens (human);Chronic myeloid leukemia - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Melanoma - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Cell cycle - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Breast cancer - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Measles - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Cell Cycle;miRNA Regulation of DNA Damage Response;miRNAs involved in DNA damage response;miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Metastatic brain tumor;Signaling Pathways in Glioblastoma;Retinoblastoma (RB) in Cancer;Wnt Signaling Pathway;PI3K-Akt Signaling Pathway;Tumor suppressor activity of SMARCB1;G1 to S cell cycle control;DNA Damage Response;Gene expression (Transcription);influence of ras and rho proteins on g1 to s transition;estrogen responsive protein efp controls cell cycle and breast tumors growth;cell cycle: g1/s check point;cyclins and cell cycle regulation;Generic Transcription Pathway;Oncogene Induced Senescence;Oxidative Stress Induced Senescence;Senescence-Associated Secretory Phenotype (SASP);Cellular Senescence;Cellular responses to stress;RNA Polymerase II Transcription;Cyclin D associated events in G1;G1 Phase;p73 transcription factor network;Mitotic G1-G1/S phases;BCR;Cellular responses to external stimuli;IL-7 signaling;TGF_beta_Receptor;Coregulation of Androgen receptor activity;JAK STAT pathway and regulation;EPO signaling;C-MYB transcription factor network;Regulation of RUNX1 Expression and Activity;Cell Cycle;Wnt;VEGF;Cell Cycle, Mitotic;Transcriptional regulation by RUNX1;IL2 signaling events mediated by STAT5;Regulation of retinoblastoma protein (Consensus)

Recessive Scores

• pRec: 0.400

Intolerance Scores

• loftool: 0.125
• rvis_EVS: 0.19
• rvis_percentile_EVS: 66.82

Haploinsufficiency Scores

• pHI: 0.995
• hipred: Y
• hipred_score: 0.802
• ghis: 0.482

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.993

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cdk6
• Phenotype: neoplasm; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; 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); liver/biliary system phenotype; embryo phenotype; immune system phenotype; muscle phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;positive regulation of cell-matrix adhesion;type B pancreatic cell development;protein phosphorylation;cell cycle arrest;negative regulation of cell population proliferation;response to virus;regulation of gene expression;astrocyte development;dentate gyrus development;lateral ventricle development;gliogenesis;cell dedifferentiation;negative regulation of cell differentiation;negative regulation of myeloid cell differentiation;regulation of erythrocyte differentiation;negative regulation of monocyte differentiation;negative regulation of osteoblast differentiation;negative regulation of cell cycle;positive regulation of fibroblast proliferation;generation of neurons;negative regulation of epithelial cell proliferation;cell division;regulation of cell motility;negative regulation of cellular senescence
• Cellular component: cyclin-dependent protein kinase holoenzyme complex;ruffle;nucleus;nucleoplasm;cytoplasm;centrosome;cytosol
• Molecular function: cyclin-dependent protein serine/threonine kinase activity;protein binding;ATP binding;cyclin binding;FBXO family protein binding