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    CASP12 caspase 12 (gene/pseudogene) [ Homo sapiens (human) ]

    Gene ID: 100506742, updated on 27-Nov-2024

    Summary

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    Official Symbol
    CASP12provided by HGNC
    Official Full Name
    caspase 12 (gene/pseudogene)provided by HGNC
    Primary source
    HGNC:HGNC:19004
    See related
    MIM:608633; AllianceGenome:HGNC:19004
    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
    CASP-12; CASP12P1
    Summary
    Caspases are cysteine proteases that cleave C-terminal aspartic acid residues on their substrate molecules. This gene is most highly related to members of the ICE subfamily of caspases that process inflammatory cytokines. In rodents, the homolog of this gene mediates apoptosis in response to endoplasmic reticulum stress. However, in humans this gene contains a polymorphism for the presence or absence of a premature stop codon. The majority of human individuals have the premature stop codon and produce a truncated non-functional protein. The read-through codon occurs primarily in individuals of African descent and carriers have endotoxin hypo-responsiveness and an increased susceptibility to severe sepsis. Several alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Feb 2011]
    Annotation information
    Annotation category: suggests misassembly
    Note: Genetic polymorphisms result in both protein coding and non-coding alleles of this gene.
    Expression
    Broad expression in ovary (RPKM 2.1), endometrium (RPKM 1.1) and 14 other tissues See more
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    Genomic context

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    See CASP12 in Genome Data Viewer
    Location:
    11q22.3
    Exon count:
    9
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (104883286..104898460, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (104887413..104902580, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (104754013..104769187, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105369466 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5457 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5458 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr11:104651953-104652716 Neighboring gene uncharacterized LOC107984380 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3867 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5459 Neighboring gene NANOG hESC enhancer GRCh37_chr11:104765419-104765947 Neighboring gene caspase 4 like, pseudogene Neighboring gene uncharacterized LOC124902813 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr11:104839101-104840300 Neighboring gene caspase 4

    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
    • 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. Gender differences in expression of the human caspase-12 long variant determines susceptibility to Listeria monocytogenes infection. Yeretssian G, et al. Proc Natl Acad Sci U S A, 2009 Jun 2. PMID 19447924, Free PMC Article
    2. A possible mechanism for maintenance of the deleterious allele of human CASPASE-12. Hermel E, et al. Med Hypotheses, 2011 Nov. PMID 21872999
    3. The resveratrol attenuates ethanol-induced hepatocyte apoptosis via inhibiting ER-related caspase-12 activation and PDE activity in vitro. Liu LQ, et al. Alcohol Clin Exp Res, 2014 Mar. PMID 24224909
    4. CASPASE-12 and rheumatoid arthritis in African-Americans. Marshall L, et al. Immunogenetics, 2014 Apr. PMID 24515649, Free PMC Article
    5. Lack of association of the caspase-12 long allele with community-acquired pneumonia in people of African descent. Chen J, et al. PLoS One, 2014. PMID 24586588, Free PMC Article

    See all (49) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Human Caspase 12 Enhances NF-kappaB Activity through Activation of IKK in Nasopharyngeal Carcinoma Cells.
      Title: Human Caspase 12 Enhances NF-κB Activity through Activation of IKK in Nasopharyngeal Carcinoma Cells.
    2. Analysis of CASP12 diagnostic and prognostic values in cervical cancer based on TCGA database.
      Title: Analysis of CASP12 diagnostic and prognostic values in cervical cancer based on TCGA database.
    3. The expression of three genes (STK26, KCNT2, CASP12) was correlated with the prognosis of skin cutaneous melanoma (SCM). STK26 and KCNT2 were significantly different between normal skin and SCM. These three hub genes have potential value as predictors for accurate diagnosis and prognosis of SCM in the future.
      Title: Common Nevus and Skin Cutaneous Melanoma: Prognostic Genes Identified by Gene Co-Expression Network Analysis.
    4. study indicated the potential effect of Casp12 was on the activation of NF-kappaB by the degradation of IkappaBalpha in NPC cells.
      Title: Caspase 12 degrades IκBα protein and enhances MMP-9 expression in human nasopharyngeal carcinoma cell invasion.
    5. CASP12 genotype thus does not influence the phenotype of systemic lupus erythematosus in African-Americans
      Title: The anti-inflammatory CASPASE-12 gene does not influence SLE phenotype in African-Americans.
    6. Endoplasmic reticulum stress may be associated with apoptosis of LECs, resulting in cataract formation in diabetic patients.
      Title: Calpain and Caspase-12 Expression in Lens Epithelial Cells of Diabetic Cataracts.
    7. Endoplasmic reticulum stress related factor ATF6 and caspase-12 trigger apoptosis in neonatal hypoxic-ischemic encephalopathy.
      Title: ER stress related factor ATF6 and caspase-12 trigger apoptosis in neonatal hypoxic-ischemic encephalopathy.
    8. Expression of caspase-12 was linked to decreased systemic and adipose tissue inflammation in a cohort of African American obese children.
      Title: Caspase-12, but Not Caspase-11, Inhibits Obesity and Insulin Resistance.
    9. We found that RNA interference-induced Caspase-12 silencing increased NOD1, hBD1 and hBD2 expression
      Title: Caspase-12 silencing attenuates inhibitory effects of cigarette smoke extract on NOD1 signaling and hBDs expression in human oral mucosal epithelial cells.
    10. conclude that the functional CASP12L allele is not a marker for susceptibility and/or severity of CAP
      Title: Lack of association of the caspase-12 long allele with community-acquired pneumonia in people of African descent.
    Submit: New GeneRIF Correction See all GeneRIFs (28)

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat induces endoplasmic reticulum (ER) stress response proteins CASP12 (Caspase 12), DDIT3 (CHOP), ROS1, ERN-1 (p-IRE1), EIF2AK3 (p-PERK), and ATF6 in human brain microvascular endothelial cells (HBMECs) PubMed

    Go to the HIV-1, Human Interaction Database

    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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    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    NOT enables cysteine-type endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables cysteine-type endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    NOT enables cysteine-type endopeptidase activity IKR
    Inferred from Key Residues
    more info
    		 PubMed 
    Process Evidence Code Pubs
    NOT involved_in apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of inflammatory response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of neuron apoptotic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    part_of NLRP1 inflammasome complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    inactive caspase-12
    Names
    caspase 12 pseudogene 1

    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_028201.3 RefSeqGene

      Range
      4791..17743
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001191016.3 → NP_001177945.2  inactive caspase-12

      See identical proteins and their annotated locations for NP_001177945.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the protein coding transcript, encoding Arg (CGA, aa 125) at the polymorphic site instead of the premature translation termination codon (TGA). The encoded protein (also known as Csp12-L) has no protease activity; however, it is thought to modulate inflammation and innate immune response to endotoxins, and is a risk factor for developing severe sepsis.
      Source sequence(s)
      AP002004, AY358222, KF459667, KF495790, KF495792
      UniProtKB/Swiss-Prot
      D6RBN7, Q6UXS9
      Conserved Domains (2) summary
      smart00115
      Location:103 → 339
      CASc; Caspase, interleukin-1 beta converting enzyme (ICE) homologues
      cd08325
      Location:6 → 88
      CARD_CASP1-like; Caspase activation and recruitment domain found in Caspase-1 and related proteins

    RNA

    1. NR_034061.4 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) encodes a translation termination codon (TGA) at the polymorphic site, resulting in a truncated protein product (known as Csp12-S), thus rendering the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AP002004, KF459667, KF495790, KF495792

    2. NR_034063.4 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) is missing an exon at the 3' end compared to variant 1, and encodes a translation termination codon (TGA) at the polymorphic site, resulting in a truncated protein product, thus rendering the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AP002004, KF459667, KF495790, KF495792

    3. NR_034064.4 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) is missing an exon at the 3' end and uses an alternate donor splice site at an internal exon compared to variant 1. It encodes a translation termination codon (TGA) at the polymorphic site, resulting in a truncated protein product, thus rendering the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AP002004, KF459667, KF495790, KF495792

    4. NR_034065.4 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) is missing an internal exon compared to variant 1, and encodes a translation termination codon (TGA) at the polymorphic site, resulting in a truncated protein product, thus rendering the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AP002004, KF459667, KF495790, KF495792

    5. NR_034066.4 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) is missing 2 internal exons compared to variant 1, and encodes a translation termination codon (TGA) at the polymorphic site, resulting in a truncated protein product, thus rendering the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AP002004, KF459667, KF495790

    6. NR_034067.4 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) is missing 2 internal exons compared to variant 1, and encodes a translation termination codon (TGA) at the polymorphic site, resulting in a truncated protein product, thus rendering the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AP002004, KF459667, KF495790, KF495792

    7. NR_034068.4 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) is missing 3 internal exons compared to variant 1, and encodes a translation termination codon (TGA) at the polymorphic site, resulting in a truncated protein product, thus rendering the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AP002004, KF459667, KF495790

    8. NR_034070.4 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9) contains an additional internal exon compared to variant 1, resulting in a frame-shift and premature translation termination, thus rendering the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AP002004, KF459667, KF495790, KF495792

    9. NR_034071.4 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (10) contains an additional internal exon and is missing another exon compared to variant 1, resulting in a frame-shift and premature translation termination, thus rendering the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AP002004, KF459667, KF495790, KF495792

    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
      104883286..104898460 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_025791791.1 Reference GRCh38.p14 PATCHES

      Range
      182419..197593 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      104887413..104902580 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NR_000035.2: Suppressed sequence

      Description
      NR_000035.2: This RefSeq was permanently suppressed because it is now thought that this gene does encode a protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6UXS9.3 GenPept UniProtKB/Swiss-Prot:Q6UXS9

    Gene LinkOut

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

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