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    CDKN1C cyclin dependent kinase inhibitor 1C [ Homo sapiens (human) ]

    Gene ID: 1028, updated on 12-Nov-2024

    Summary

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    Official Symbol
    CDKN1Cprovided by HGNC
    Official Full Name
    cyclin dependent kinase inhibitor 1Cprovided by HGNC
    Primary source
    HGNC:HGNC:1786
    See related
    Ensembl:ENSG00000129757 MIM:600856; AllianceGenome:HGNC:1786
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    BWS; WBS; p57; BWCR; KIP2; p57Kip2
    Summary
    This gene is imprinted, with preferential expression of the maternal allele. The encoded protein is a tight-binding, strong inhibitor of several G1 cyclin/Cdk complexes and a negative regulator of cell proliferation. Mutations in this gene are implicated in sporadic cancers and Beckwith-Wiedemann syndorome, suggesting that this gene is a tumor suppressor candidate. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]
    Expression
    Biased expression in placenta (RPKM 87.0), fat (RPKM 42.6) and 9 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See CDKN1C in Genome Data Viewer
    Location:
    11p15.4
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (2883218..2885775, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (2972459..2975017, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (2904448..2907005, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene potassium voltage-gated channel subfamily Q member 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:2878979-2879960 Neighboring gene KCNQ1 antisense RNA 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2884189-2884886 Neighboring gene CRISPRi-validated cis-regulatory element chr11.592 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:2890154-2890662 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:2904223-2904722 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2906831-2907666 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2905995-2906830 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2907667-2908502 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2913065-2913864 Neighboring gene SLC22A18 antisense RNA Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3074 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:2924695-2925196 Neighboring gene KCNQ1 downstream neighbor Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:2933345-2934048 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:2935457-2936158 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2949927-2950535 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:2950536-2951145 Neighboring gene solute carrier family 22 member 18 Neighboring gene pleckstrin homology like domain family A member 2

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. An 11p15 imprinting centre region 2 deletion in a family with Beckwith Wiedemann syndrome provides insights into imprinting control at CDKN1C. Algar E, et al. PLoS One, 2011. PMID 22205991, Free PMC Article
    2. Oligodendroglial lineage cells express nuclear p57kip2 in multiple sclerosis lesions. Pfeifenbring S, et al. Glia, 2013 Aug. PMID 23828667
    3. Clinical implications of p57 KIP2 expression in breast cancer. Xu XY, et al. Asian Pac J Cancer Prev, 2012. PMID 23244105
    4. A novel mutation in CDKN1C in sibs with Beckwith-Wiedemann syndrome and cleft palate, sensorineural hearing loss, and supernumerary flexion creases. Kantaputra PN, et al. Am J Med Genet A, 2013 Jan. PMID 23197429
    5. Cell cycle regulator Cdkn1c (p57/KIP2) shows distinct expression in epidermal differentiation. Hildebrand J, et al. Eur J Dermatol, 2012 Sep-Oct. PMID 23008285

    See all (250) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Expanded phenotype and cancer risk in patients with Beckwith-Wiedemann spectrum caused by CDKN1C variants.
      Title: Expanded phenotype and cancer risk in patients with Beckwith-Wiedemann spectrum caused by CDKN1C variants.
    2. STK40 inhibits trophoblast fusion by mediating COP1 ubiquitination to degrade P57[Kip2].
      Title: STK40 inhibits trophoblast fusion by mediating COP1 ubiquitination to degrade P57(Kip2).
    3. Promoter methylation and enhanced SKP2 are associated with the downregulation of CDKN1C in cervical squamous cell carcinoma.
      Title: Promoter methylation and enhanced SKP2 are associated with the downregulation of CDKN1C in cervical squamous cell carcinoma.
    4. MYOD-SKP2 axis boosts tumorigenesis in fusion negative rhabdomyosarcoma by preventing differentiation through p57[Kip2] targeting.
      Title: MYOD-SKP2 axis boosts tumorigenesis in fusion negative rhabdomyosarcoma by preventing differentiation through p57(Kip2) targeting.
    5. Structure-Function Analysis of p57KIP2 in the Human Pancreatic Beta Cell Reveals a Bipartite Nuclear Localization Signal.
      Title: Structure-Function Analysis of p57KIP2 in the Human Pancreatic Beta Cell Reveals a Bipartite Nuclear Localization Signal.
    6. Exploiting the fibroblast growth factor receptor-1 vulnerability to therapeutically restrict the MYC-EZH2-CDKN1C axis-driven proliferation in Mantle cell lymphoma.
      Title: Exploiting the fibroblast growth factor receptor-1 vulnerability to therapeutically restrict the MYC-EZH2-CDKN1C axis-driven proliferation in Mantle cell lymphoma.
    7. PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDKN1C and SMC1A.
      Title: PIK3R3 is upregulated in liver cancer and activates Akt signaling to control cancer growth by regulation of CDKN1C and SMC1A.
    8. Identification and targeting of a HES1-YAP1-CDKN1C functional interaction in fusion-negative rhabdomyosarcoma.
      Title: Identification and targeting of a HES1-YAP1-CDKN1C functional interaction in fusion-negative rhabdomyosarcoma.
    9. High Maternal Serum Estradiol in First Trimester of Multiple Pregnancy Contributes to Small for Gestational Age via DNMT1-Mediated CDKN1C Upregulation.
      Title: High Maternal Serum Estradiol in First Trimester of Multiple Pregnancy Contributes to Small for Gestational Age via DNMT1-Mediated CDKN1C Upregulation.
    10. Loss of p57 Expression in Conceptions Other Than Complete Hydatidiform Mole: A Case Series With Emphasis on the Etiology, Genetics, and Clinical Significance.
      Title: Loss of p57 Expression in Conceptions Other Than Complete Hydatidiform Mole: A Case Series With Emphasis on the Etiology, Genetics, and Clinical Significance.
    Submit: New GeneRIF Correction See all GeneRIFs (195)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2020-09-25)

    ClinGen Genome Curation PagePubMed
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2020-09-25)

    ClinGen Genome Curation PagePubMed

    EBI GWAS Catalog

    Description
    Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cyclin-dependent protein serine/threonine kinase inhibitor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables molecular function inhibitor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein kinase inhibitor activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein-containing complex binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in negative regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of cyclin-dependent protein kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of epithelial cell proliferation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of epithelial cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of mitotic cell cycle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of DNA-templated transcription IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in positive regulation of transforming growth factor beta receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    cyclin-dependent kinase inhibitor 1C
    Names
    cyclin-dependent kinase inhibitor 1C (p57, Kip2)
    cyclin-dependent kinase inhibitor p57

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_008022.1 RefSeqGene

      Range
      5001..7548
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_533

    mRNA and Protein(s)

    1. NM_000076.2 → NP_000067.1  cyclin-dependent kinase inhibitor 1C isoform a

      See identical proteins and their annotated locations for NP_000067.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a). Variants 1 and 3 both encode isoform a.
      Source sequence(s)
      AC013791, BC039188, CD676249, U22398
      Consensus CDS
      CCDS7738.1
      UniProtKB/Swiss-Prot
      P49918
      UniProtKB/TrEMBL
      A0A0G2JPX0
      Related
      ENSP00000411552.2, ENST00000430149.3
      Conserved Domains (1) summary
      pfam02234
      Location:32 → 78
      CDI; Cyclin-dependent kinase inhibitor

    2. NM_001122630.2 → NP_001116102.1  cyclin-dependent kinase inhibitor 1C isoform b

      See identical proteins and their annotated locations for NP_001116102.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Variants 2 and 3 both encode isoform b.
      Source sequence(s)
      AC013791, BC039188, CD676249, U22398
      Consensus CDS
      CCDS44519.1
      UniProtKB/TrEMBL
      B2D1N3
      Related
      ENSP00000411257.2, ENST00000440480.8
      Conserved Domains (1) summary
      pfam02234
      Location:21 → 67
      CDI; Cyclin-dependent kinase inhibitor

    3. NM_001122631.2 → NP_001116103.1  cyclin-dependent kinase inhibitor 1C isoform b

      See identical proteins and their annotated locations for NP_001116103.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence and uses an alternate splice junction in the 3' UTR compared to variant 1. The resulting isoform (b) is shorter at the N-terminus compared to isoform a. Variants 2 and 3 both encode isoform b.
      Source sequence(s)
      AC013791, BC039188, BM673714, CD676249, U22398
      Consensus CDS
      CCDS44519.1
      UniProtKB/TrEMBL
      B2D1N3
      Conserved Domains (1) summary
      pfam02234
      Location:21 → 67
      CDI; Cyclin-dependent kinase inhibitor

    4. NM_001362474.2 → NP_001349403.1  cyclin-dependent kinase inhibitor 1C isoform a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 3' UTR compared to variant 1. Variants 1 and 3 both encode isoform a.
      Source sequence(s)
      AC013791
      Consensus CDS
      CCDS7738.1
      UniProtKB/Swiss-Prot
      P49918
      UniProtKB/TrEMBL
      A0A0G2JPX0
      Related
      ENSP00000413720.3, ENST00000414822.8
      Conserved Domains (1) summary
      pfam02234
      Location:32 → 78
      CDI; Cyclin-dependent kinase inhibitor

    5. NM_001362475.2 → NP_001349404.1  cyclin-dependent kinase inhibitor 1C isoform c

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR and uses an alternate splice site in the coding region, compared to variant 1, which results in a frameshift. The encoded protein (isoform c) has a shorter and distinct C-terminus, compared to isoform a.
      Source sequence(s)
      AC013791
      Consensus CDS
      CCDS86169.1
      UniProtKB/TrEMBL
      A0A2R8YFP9
      Related
      ENSP00000496631.1, ENST00000647251.1
      Conserved Domains (1) summary
      pfam02234
      Location:22 → 68
      CDI; Cyclin-dependent kinase inhibitor

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      2883218..2885775 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NT_187585.1 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      115397..117985 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      2972459..2975017 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P49918.1 GenPept UniProtKB/Swiss-Prot:P49918

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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