CDKN1A
cyclin dependent kinase inhibitor 1A
Basic information
Region (hg38): 6:36676460-36687397
Previous symbols: [ "CDKN1" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the CDKN1A 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 | 7 | |||||
| missense | 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 | 4 | 7 | 2 |
Variants in CDKN1A
This is a list of pathogenic ClinVar variants found in the CDKN1A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 6-36684112-C-T | Benign (May 29, 2018) | |||
| 6-36684113-G-A | Benign (Apr 24, 2018) | |||
| 6-36684128-T-C | Likely benign (Aug 01, 2024) | |||
| 6-36684160-G-A | not specified | Uncertain significance (Nov 18, 2022) | ||
| 6-36684175-T-G | not specified | Uncertain significance (Jan 30, 2024) | ||
| 6-36684182-C-T | Likely benign (Dec 01, 2023) | |||
| 6-36684194-C-A | CIP1/WAF1 TUMOR-ASSOCIATED POLYMORPHISM 1 | Benign (Jul 01, 1996) | ||
| 6-36684194-C-T | Likely benign (Apr 01, 2024) | |||
| 6-36684198-G-C | not specified | Uncertain significance (Oct 09, 2024) | ||
| 6-36684220-G-T | not specified | Uncertain significance (Aug 30, 2024) | ||
| 6-36684243-C-T | Malignant tumor of urinary bladder | Pathogenic (-) | ||
| 6-36684244-G-A | not specified | Uncertain significance (Apr 09, 2024) | ||
| 6-36684247-G-C | not specified | Uncertain significance (-) | ||
| 6-36684255-G-A | not specified | Uncertain significance (Dec 22, 2023) | ||
| 6-36684255-G-C | not specified | Uncertain significance (-) | ||
| 6-36684266-C-T | Likely benign (Apr 01, 2024) | |||
| 6-36684296-GG-AA | Malignant tumor of urinary bladder | Uncertain significance (-) | ||
| 6-36684315-G-A | not specified | Uncertain significance (Dec 10, 2024) | ||
| 6-36684341-G-C | Likely benign (Oct 01, 2022) | |||
| 6-36684352-G-A | not specified | Likely benign (Sep 01, 2024) | ||
| 6-36684374-A-T | Likely benign (Sep 01, 2024) | |||
| 6-36684429-C-G | not specified | Uncertain significance (Oct 16, 2023) | ||
| 6-36684451-G-A | Conflicting classifications of pathogenicity (Nov 01, 2024) | |||
| 6-36685748-C-G | not provided (-) | |||
| 6-36685767-A-G | Likely benign (Mar 01, 2023) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| CDKN1A | protein_coding | protein_coding | ENST00000405375 | 2 | 10812 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00186 | 0.739 | 125721 | 0 | 10 | 125731 | 0.0000398 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.416 | 104 | 117 | 0.892 | 0.00000865 | 1024 |
| Missense in Polyphen | 35 | 39.55 | 0.88494 | 348 | ||
| Synonymous | 0.642 | 40 | 45.5 | 0.879 | 0.00000290 | 371 |
| Loss of Function | 0.871 | 5 | 7.59 | 0.659 | 5.61e-7 | 61 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000215 | 0.000213 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000444 | 0.0000440 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: May be involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (PubMed:11595739). {ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:8242751, ECO:0000269|PubMed:9106657}.;
- Pathway
- PI3K-Akt signaling pathway - Homo sapiens (human);Non-small cell lung cancer - Homo sapiens (human);Chronic myeloid leukemia - Homo sapiens (human);Gastric cancer - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Kaposi,s sarcoma-associated herpesvirus infection - Homo sapiens (human);Renal cell carcinoma - Homo sapiens (human);Melanoma - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Bladder cancer - Homo sapiens (human);Cell cycle - Homo sapiens (human);HIF-1 signaling pathway - Homo sapiens (human);Jak-STAT signaling pathway - Homo sapiens (human);p53 signaling pathway - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Breast cancer - Homo sapiens (human);ErbB signaling pathway - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Glioma - Homo sapiens (human);Prostate cancer - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Hepatitis C - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Thyroid cancer - Homo sapiens (human);Pancreatic cancer - Homo sapiens (human);Endometrial cancer - Homo sapiens (human);Colorectal cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Vincristine Action Pathway;Vinblastine Action Pathway;Vinorelbine Action Pathway;Vindesine Action Pathway;Cell Cycle;Androgen receptor signaling pathway;AMP-activated Protein Kinase (AMPK) Signaling;miRNA Regulation of DNA Damage Response;miRNAs involved in DNA damage response;TP53 Network;Cell Cycle Checkpoints;Integrated Cancer Pathway;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Signaling Pathways in Glioblastoma;Adipogenesis;Retinoblastoma (RB) in Cancer;ATM Signaling Pathway;Primary Focal Segmental Glomerulosclerosis FSGS;Aryl Hydrocarbon Receptor;Bladder Cancer;Apoptosis-related network due to altered Notch3 in ovarian cancer;Vitamin D Receptor Pathway;DNA Damage-Telomere Stress Induced Senescence;miR-517 relationship with ARCN1 and USP1;Photodynamic therapy-induced AP-1 survival signaling.;Hepatitis C and Hepatocellular Carcinoma;TGF-beta Signaling Pathway;LncRNA-mediated mechanisms of therapeutic resistance;Association Between Physico-Chemical Features and Toxicity Associated Pathways;TP53 Regulates Transcription of Cell Cycle Genes;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Oxidative Damage;miRNA regulation of prostate cancer signaling pathways;Liver steatosis AOP;Interleukin-4 and 13 signaling;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors;Transcriptional regulation by RUNX3;Endometrial cancer;PI3K-Akt Signaling Pathway;Chromosomal and microsatellite instability in colorectal cancer;Type 2 papillary renal cell carcinoma;G1 to S cell cycle control;Notch Signaling Pathway;Senescence and Autophagy in Cancer;ErbB Signaling Pathway;DNA Damage Response;DNA Damage Response (only ATM dependent);Transcriptional regulation by RUNX2;Disease;RUNX3 regulates CDKN1A transcription;Signal Transduction;Gene expression (Transcription);Transcriptional regulation by RUNX3;hypoxia and p53 in the cardiovascular system;influence of ras and rho proteins on g1 to s transition;erythropoietin mediated neuroprotection through nf-kb;cell cycle: g1/s check point;effects of calcineurin in keratinocyte differentiation;cyclins and cell cycle regulation;Generic Transcription Pathway;Formation of Senescence-Associated Heterochromatin Foci (SAHF);DNA Damage/Telomere Stress Induced Senescence;Senescence-Associated Secretory Phenotype (SASP);Cellular Senescence;Cellular responses to stress;RNA Polymerase II Transcription;Transcriptional activation of cell cycle inhibitor p21 ;Transcriptional activation of p53 responsive genes ;p53-Dependent G1 DNA Damage Response;p53-Dependent G1/S DNA damage checkpoint;G1/S DNA Damage Checkpoints;Cell Cycle Checkpoints;Hedgehog;Cyclin D associated events in G1;G1 Phase;SCF(Skp2)-mediated degradation of p27/p21;p73 transcription factor network;Cyclin E associated events during G1/S transition ;Mitotic G1-G1/S phases;Cyclin A:Cdk2-associated events at S phase entry;S Phase;cell cycle: g2/m checkpoint;Cellular responses to external stimuli;TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest;p53 signaling pathway;TGF_beta_Receptor;TP53 Regulates Transcription of Cell Cycle Genes;Glucocorticoid receptor regulatory network;The role of GTSE1 in G2/M progression after G2 checkpoint;Validated transcriptional targets of TAp63 isoforms;rb tumor suppressor/checkpoint signaling in response to dna damage;G2/M Transition;Mitotic G2-G2/M phases;PIP3 activates AKT signaling;G1/S Transition;C-MYB transcription factor network;Transcriptional Regulation by TP53;Angiopoietin receptor Tie2-mediated signaling;Notch signaling pathway;Direct p53 effectors;TFAP2 (AP-2) family regulates transcription of cell cycle factors;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors;Constitutive Signaling by AKT1 E17K in Cancer;PI3K/AKT Signaling in Cancer;Cell Cycle;AKT phosphorylates targets in the cytosol;Cell Cycle, Mitotic;Intracellular signaling by second messengers;Diseases of signal transduction;Validated targets of C-MYC transcriptional repression;Signaling events mediated by HDAC Class III;Class I PI3K signaling events mediated by Akt;Regulation of retinoblastoma protein;Regulation of nuclear SMAD2/3 signaling;E2F transcription factor network;Signaling events mediated by PRL
(Consensus)
Recessive Scores
- pRec
- 0.0908
Intolerance Scores
- loftool
- 0.232
- rvis_EVS
- 0.46
- rvis_percentile_EVS
- 78.46
Haploinsufficiency Scores
- pHI
- 0.969
- hipred
- Y
- hipred_score
- 0.581
- ghis
- 0.433
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.995
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Cdkn1a
- 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; 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; craniofacial phenotype; muscle phenotype; no phenotypic analysis (no description of morphological, physiological or behavioral information presented); cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; embryo phenotype; neoplasm; 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); reproductive system phenotype; 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); vision/eye phenotype; 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); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; skeleton phenotype; renal/urinary system phenotype;
Zebrafish Information Network
- Gene name
- cdkn1a
- Affected structure
- regulation of mitotic cell cycle, embryonic
- Phenotype tag
- abnormal
- Phenotype quality
- disrupted
Gene ontology
- Biological process
- regulation of cyclin-dependent protein serine/threonine kinase activity;G1/S transition of mitotic cell cycle;G2/M transition of mitotic cell cycle;regulation of transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;cellular response to DNA damage stimulus;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;cell cycle arrest;Ras protein signal transduction;heart development;negative regulation of cell population proliferation;response to toxic substance;response to X-ray;response to organonitrogen compound;positive regulation of cell death;cytokine-mediated signaling pathway;negative regulation of cell growth;animal organ regeneration;cellular response to extracellular stimulus;cellular response to amino acid starvation;cellular response to heat;negative regulation of phosphorylation;response to drug;negative regulation of apoptotic process;negative regulation of cyclin-dependent protein serine/threonine kinase activity;positive regulation of protein kinase activity;response to arsenic-containing substance;positive regulation of fibroblast proliferation;protein stabilization;response to corticosterone;response to hyperoxia;intestinal epithelial cell maturation;cellular response to ionizing radiation;cellular response to UV-B;mitotic cell cycle arrest;cellular senescence;replicative senescence;stress-induced premature senescence;intrinsic apoptotic signaling pathway;negative regulation of cyclin-dependent protein kinase activity;positive regulation of cyclin-dependent protein kinase activity;negative regulation of vascular smooth muscle cell proliferation;negative regulation of cardiac muscle tissue regeneration;negative regulation of G1/S transition of mitotic cell cycle;positive regulation of reactive oxygen species metabolic process
- Cellular component
- cyclin-dependent protein kinase holoenzyme complex;nucleus;nucleoplasm;nucleolus;cytosol;nuclear body;protein-containing complex;perinuclear region of cytoplasm;PCNA-p21 complex
- Molecular function
- cyclin-dependent protein serine/threonine kinase activity;protein kinase inhibitor activity;cyclin-dependent protein serine/threonine kinase inhibitor activity;protein binding;protein kinase binding;cyclin-dependent protein kinase activating kinase activity;cyclin binding;ubiquitin protein ligase binding;protein-containing complex binding;metal ion binding