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Symbol CDKN1A contributors: npt/mct - updated : 20-09-2014
HGNC name cyclin-dependent kinase inhibitor 1A (p21, Cip1)
HGNC id 1784
Location 6p21.2      Physical location : 36.646.458 - 36.655.108
Synonym name
  • cyclin-dependent kinase inhibitor, p21
  • wild-type p53-activated fragment 1
  • DNA synthesis inhibitor
  • CDK-interacting protein 1
  • melanoma differentiation-associated protein 6
  • Synonym symbol(s) CDKN1, CIP1, WAF1, P21, SDI1, CAP20, MDA6, p21CIP1, p21Cip1/Waf1
    TYPE functioning gene
    STRUCTURE 10.88 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   silencer   transcription factor
    text structure
  • BCL11B is recruited to the gene promoter, silenced CDKN1A gene transcription through interactions with histone deacetylases and methyltransferases
  • a novel AP-2 binding site within the proximal promoter of the CDKN1A gene, required for optimal, TP53-independent expression of CDKN1A
  • three putative ARID3A binding sites were found in the CDKN1A promoter region
  • a cis-acting element in the promoter interacts with TSG101 and is required for promoter repression
  • MAPPING cloned Y linked N status confirmed
    Physical map
    DEF6 6p21.33-p21.1 differentially expressed in FDCP 6 homolog (mouse) PPARD 6p21.2-p21.1 peroxisome proliferative activated receptor, delta MKRNP2 6p21.1 makorin, ring finger protein, pseudogene 2 FANCE 6p22-p21 Fanconi anemia, complementation group E RPL10A 6p21.3 ribosomal protein L10a TEAD3 6p21.2 TEA domain family member 3 TULP1 6p21.3 tubby like protein 1 LOC389382 6 similar to Rps15a protein FKBP5 6p21.3-p21.2 FK506 binding protein 5 C6orf81 6p21.31 chromosome 6 open reading frame 81 LOC389383 6 similar to AAAL3045 LOC340204 6p21.31 similar to precursor peptide CLPS 6p22-p21.1 colipase, pancreatic MGC33835 6p21.31 hypothetical protein MGC33835 SRPK1 6p213-p21.2 SFRS protein kinase 1 SLC26A8 6p21 solute carrier family 26, member 8 MAPK14 6p21.2 mitogen-activated protein kinase 14 MAPK13 6p21.1 mitogen-activated protein kinase 13 BRPF3 6p21 bromodomain and PHD finger containing, 3 PNPLA1 6p21.31 patatin-like phospholipase domain containing 1 LOC389384 6 similar to RIKEN cDNA 4930539E08 ETV7 6p21 ets variant gene 7 (TEL2 oncogene ) STEPP 6p21.31 small testis-specific peroxisomal protein C6orf69 6p21.31 chromosome 6 open reading frame 69 STK38 6p21 serine/threonine kinase 38 SFRS3 11p15.1 splicing factor, arginine/serine-rich 3 LOC389385 6 similar to Cytosol aminopeptidase (Leucine aminopeptidase) (LAP) (Leucyl aminopeptidase) (Proline aminopeptidase) (Prolyl aminopeptidase) LOC389386 6 similar to Cytosol aminopeptidase (Leucine aminopeptidase) (LAP) (Leucyl aminopeptidase) (Proline aminopeptidase) (Prolyl aminopeptidase) CDKN1A 6p21.2 cyclin-dependent kinase inhibitor 1A (p21, Cip1) LOC346190 6p21.31 similar to hypothetical protein FLJ31614 LOC391917 6 similar to putative G-protein coupled receptor CPNE5 6p21.1 copine V PPIL1 6p21.1 peptidylprolyl isomerase (cyclophilin)-like 1 C6orf89 6p21.31 chromosome 6 open reading frame 89 PI16 6p21.31 protease inhibitor 16 MTCH1 6pter-p24.1 mitochondrial carrier homolog 1 (C. elegans) FGD2 6p21.2 FGD1 family, member 2 LOC285849 6p21.31 similar to cytochrome c oxidase subunit VIa polypeptide 1 precursor; cytochrome C oxidase subunit VIa homolog LOC389387 6 similar to 60S ribosomal protein L12 PIM1 6p21.2 pim-1 oncogene C6orf128 6p21.31-p21.2 chromosome 6 open reading frame 128 C6orf197 6p21.2 chromosome 6 open reading frame 197 RNF8 6p21.3 ring finger protein (C3HC4 type) 8 KIAA0082 6p21.2 ring finger protein (C3HC4 type) 8 C6orf129 6p21.2 chromosome 6 open reading frame 129 MDGA1 6p21 MAM domain containing glycosylphosphatidylinositol anchor 1 TEX27 6pter-p22.3 testis expressed sequence 27
    TRANSCRIPTS type messenger
  • two transcripts encoding for the same product
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 splicing 2168 18.12 164 - 1999 9925645
    lacking an internal sequence segment in the 5' UTR
    4 splicing 2281 18.12 164 - 1999 9925645
    3 - 2119 - 164 - -
    3 - 2284 - 164 - -
    - - 2325 - 198 - -
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately
    Digestivemouth   moderately
     salivary gland   moderately
     stomach   highly
    Endocrinepancreas   moderately
    Hearing/Equilibriumearinnercochlea highly
    Lymphoid/Immunethymus   moderately
    Nervousnerve   highly
    Reproductivefemale systemuteruscervix moderately
    Respiratorylung   predominantly
    Skin/Tegumentskin   highly
    Visualeye   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cell lineage
    cell lines
    at STAGE
    physiological period embryo
    cell cycle     cell cycle, interphase, G1
    Text embryonic tissue
  • N-terminal region required for repression of gene expression of CCNE2 and other genes
  • a CDK inhibitory domain
  • a proline-rich domain
  • an acidic repeat region
  • a conserved C terminal domain hybridizing with WI-7311, WI-10190
    interspecies homolog to rattus Cdkn1a (76.54 pc)
    homolog to murine Cdkn1a (79.25 pc)
  • CDK inhibitor family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    text apoptosis
    basic FUNCTION
  • wild type p53-activated fragment 1 mediating the cell cycle G1 phase arrest in response of various stress stimuli
  • involved in an age-dependent increase in cell cycle negative regulation of the Human Corneal Endothelial Cells (HCEC)
  • may be responsible, at least in part, for the reduced proliferative response observed in HCECs from older donors
  • upstream regulator of DNMT1 expression, and negatively regulates DNMT1 expression in mammalian cells
  • major cell cycle regulator of the response to DNA damage, senescence and tumor suppression
  • plays an essential role in promoting cell cycle exit in endocrine progenitors downstream of NEUROG3)
  • exerts a repressive effect on a relevant number of genes controlling S phase and mitosis
  • is a crucial downstream effector of TRIM39 mediating G1/S transition and DNA damage-induced G2 arrest
  • is necessary for proper control of the cell cycle and premature senescence
  • CELLULAR PROCESS cell cycle
  • CDK inhibitor controlling differentiation of skeletal muscle and alveoli in the lung in parallel with P21 and myogenin
  • suppressor of malignant skin tumor formation and as a determinant of keratinocyte stem-cell potential
  • regulator at G1 cell cylce exit in megacaryocytes
    CDKN1A-EP300-DNMT1 pathway may play a pivotal role to ensure regulated DNMT1 expression and DNA methylation in mammalian cell division
    a component
  • CDKN1A/NFYA/PLK1 axis critical for maintaining the checkpoint function of TP53 to prevent mitotic death in the DNA damage-induced response
    small molecule
  • TYMS
  • inhibiting CDK2, CDK4 complexes
  • inhibiting cycle progression by interacting with G1 cyclin/CDK complexes and PCNA
  • CCNE2
  • TFAP2A binds CDKN1A to two regions of the promoter: the proximal region where the AP-2 site lies and upstream near the major TP53 binding site
  • SSBP1 directly binds CDKN1A and this interaction may prevent CDKN1A from ubiquitin-mediated degradation
  • new function of SRSF2 in the process of cellular senescence and CDKN1A is a key target of SRSF2 in this setting
  • acted in part to mediate growth suppression by ARID1A
  • cooperative and interdependent roles for ARID3A and TP53 in the transcriptional activation of CDKN1A in response to DNA damage
  • KDM8 physiologically moderates embryonic cell proliferation through the epigenetic control of CDKN1A expression
  • RNF144B is a potentially critical component of epithelial homeostasis, acting downstream of TP63 to regulate cellular levels of CDKN1A and TP63
  • HIC1 is a direct transcriptional repressor of CDKN1A and is a key player in the regulation of the DNA damage response
  • KAT5-mediated CDKN1A acetylation is a novel and essential regulatory process required for CDKN1A-dependent DNA damage-induced cell-cycle arrest
  • Aurora B represses CDKN1A, preventing delayed DNA replication, CDK inhibition and premature mitotic exit
  • RNF114 activates cell cycle progression and suppresses cellular senescence through the RING domain-mediated degradation of CDKN1A
  • unexpected role of MAPK14 in cell cycle regulation in response to Aurora B inhibition, by promoting the transcriptional elongation of the cell cycle inhibitor CDKN1A
  • FMN2 is a crucial protein involved in the control of CDKN1A (
  • CDKN2A stabilizes the CDKN1A mRNA through negative regulation of the mRNA decay-promoting HNRNPD protein
  • has dual effects under HSPA9-depleted conditions, i.e., mediating cell cycle arrest while limiting cell death
  • transcriptional repression of BMP2 by CDKN1A links quiescence to neural stem cell maintenance
  • TSG101 protein interacts with and down-regulates the promoter of CDKN1A tumor suppressor gene
  • RBM24 is a target gene of the TP53 protein, and can regulate CDKN1A expression via mRNA stability
  • TOP3A binds to the TP53 and CDKN1A promoters and positively regulates their expression, contributing to the TP53-mediated tumor suppression
  • DUX4 might potentially induce proliferation inhibition and G1 phase arrest through upregulation of CDKN1A
  • RASSF6 triggers CDKN1A accumulation to induce G 1 cell cycle arrest and promote apoptosis upon exposure to pro-apoptotic agents
  • TWIST2 directly regulated CDKN1A in hematopoietic cells and whose silence promoted cell proliferation and cell cycle progression, this direct regulation of CDKN1A by TWIST2 has a role in its tumor-suppressor function in AML (acute myeloid leukemia)
  • CDKN1A/CCNE1 pathway is crucial in modulating the anticlastogenic function of BMI1
  • cell & other
    activated by TP53
    KLF1 (directly activates CDKN1A by proximal promoter and novel intronic regulatory regions during erythroid differentiation)
    induced by chimeric oncoprotein SS18-SSX1 for suppression of cell growth
    low concentration of Cl-
    inhibited by AMPHL in early stage of muscle differentiation program
    repressed by TYMS
    ZBTB2 by a direct interaction with TP53 and SP1
    Phosphorylated by PIM2, that phosphorylates CDKN1A on Thr145
    Other cleaved by caspase 3 in the earlier stage of apoptosis
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    papillary thyroid carcinoma
    tumoral     --low  
    in adult T-cell leukemia/lymphoma (ATLL) cells may be a key player in ATLL leukemogenesis, and the abnormal genomic methylation may influence the expression of not only HTLV-1 TAX but also CDKN1A during long-term development of ATLL from the HTLV-1-infected T lymphocytes
  • esophageal cancer, cervical cancer
  • to advanced prostate carcinoma
  • to colorectal cancer
  • Variant & Polymorphism other
  • variant of the codon 31 increasing in primary cervical cancer (Japanese)
  • genotype CT and TT strongly associated with advanced prostate carcinoma
  • rs1321311, near CDKN1A influences colorectal cancer risk
  • Candidate gene
  • cell free plasma expressions of CDKN1A and HIF1A were more prevalent in pregnancies complicated by hypoxia and/or IUGR
  • Therapy target
  • being a novel, unique therapeutic strategy for gastric cancer treatment via control of decreased the intracellular chloride concentration