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

Gene ID: 100506742, updated on 2-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 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)

Genotypes

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
enables cysteine-type endopeptidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
NOT enables cysteine-type endopeptidase activity involved in apoptotic process IBA
Inferred from Biological aspect of Ancestor
more info
  
NOT enables cysteine-type endopeptidase activity involved in apoptotic process 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
  
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

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