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 ... See more...

Aliases for CASP12 Gene

Aliases for CASP12 Gene

  • Caspase 12 (Gene/Pseudogene) 2 3 5
  • Caspase 12 Pseudogene 1 2 3
  • Inactive Caspase-12 3 4
  • CASP-12 3 4
  • Caspase 12 2
  • EC 3.4.22 51
  • CASP12P1 3
  • CASP12 5

External Ids for CASP12 Gene

Previous HGNC Symbols for CASP12 Gene

  • CASP12P1

Previous GeneCards Identifiers for CASP12 Gene

  • GC11M104261
  • GC11M104757

Summaries for CASP12 Gene

Entrez Gene Summary for CASP12 Gene

  • 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]

GeneCards Summary for CASP12 Gene

CASP12 (Caspase 12 (Gene/Pseudogene)) is a Protein Coding gene. Among its related pathways are VEGF Pathway (Tocris) and Prion diseases. Gene Ontology (GO) annotations related to this gene include cysteine-type endopeptidase activity and cysteine-type endopeptidase activity involved in execution phase of apoptosis. An important paralog of this gene is CASP4.

UniProtKB/Swiss-Prot Summary for CASP12 Gene

  • Has no protease activity. May reduce cytokine release in response to bacterial lipopolysaccharide during infections. Reduces activation of NF-kappa-B in response to TNF.

Tocris Summary for CASP12 Gene

  • Caspases (cysteinyl aspartate proteases) are involved in the signaling pathways of apoptosis, necrosis and inflammation. These enzymes can be divided into initiators and effectors. The initiator isoforms are activated by, and interact with, upstream adaptor molecules.

Additional gene information for CASP12 Gene

No data available for CIViC Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CASP12 Gene

Genomics for CASP12 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CASP12 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH11J104897 Promoter/Enhancer 1 Ensembl ENCODE CraniofacialAtlas 617.1 +0.3 338 1.5 RELB JUN POLR2A TBX21 ATF7 MTA2 CASP12 CASP4LP HSALNG0086867 PDGFD
GH11J104162 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 14.6 +735.3 735269 3.2 PRDM10 ZNF629 CTCF ZNF692 ZNF7 ZIC2 PATZ1 POLR2A EZH2 ZNF600 PDGFD CASP12 DDI1
GH11J104965 Promoter/Enhancer 1.9 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 11.4 -69.1 -69067 4.9 GATAD2A TEAD4 REST POLR2A GABPA RELA IRF2 IKZF2 SP1 CEBPA CASP4 lnc-CASP5-4 CASP4LP CASP5 CASP12 CARD17 CARD16 MN309300
GH11J104892 Enhancer 0.6 Ensembl ENCODE 17.1 +4.4 4378 3.8 ATF7 BHLHE40 ATF2 NANOG CASP12 HSALNG0086867 PDGFD
GH11J104694 Enhancer 0.9 FANTOM5 Ensembl ENCODE 11.1 +203.8 203769 2.2 CEBPB JUN EP300 TCF7L2 JUND POLR2A lnc-CASP4-4 CARD17 CASP12 CASP4LP CARD16 CASP4 CASP5 HSALNG0086860 LOC105369466 PDGFD
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CASP12 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CASP12

Top Transcription factor binding sites by QIAGEN in the CASP12 gene promoter:
  • AP-4
  • ATF-2
  • Evi-1
  • FOXO4
  • HNF-3beta
  • ITF-2
  • p53
  • Pbx1a
  • Tal-1beta

Genomic Locations for CASP12 Gene

Genomic Locations for CASP12 Gene
chr11:104,885,718-104,898,670
(GRCh38/hg38)
Size:
12,953 bases
Orientation:
Minus strand
chr11:104,756,445-104,769,397
(GRCh37/hg19)
Size:
12,953 bases
Orientation:
Minus strand

Genomic View for CASP12 Gene

Genes around CASP12 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CASP12 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CASP12 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CASP12 Gene

Proteins for CASP12 Gene

  • Protein details for CASP12 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6UXS9-CASPC_HUMAN
    Recommended name:
    Inactive caspase-12
    Protein Accession:
    Q6UXS9
    Secondary Accessions:
    • D6RBN7

    Protein attributes for CASP12 Gene

    Size:
    341 amino acids
    Molecular mass:
    38907 Da
    Quaternary structure:
    No Data Available

    Alternative splice isoforms for CASP12 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CASP12 Gene

Selected DME Specific Peptides for CASP12 Gene

Q6UXS9:
  • SMTRYFYLFPG
  • HVEKDFIAF
  • SSTPHNVSWR
  • DKPKVII
  • LHDDTIF
  • SDSTFLV

Post-translational modifications for CASP12 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Domains & Families for CASP12 Gene

Gene Families for CASP12 Gene

Protein Domains for CASP12 Gene

InterPro:
Blocks:
  • CARD interaction domain
  • Interleukin-1B converting enzyme signature
ProtoNet:

Suggested Antigen Peptide Sequences for CASP12 Gene

GenScript: Design optimal peptide antigens:
  • Inactive caspase-12 (CASPC_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q6UXS9

UniProtKB/Swiss-Prot:

CASPC_HUMAN :
  • Belongs to the peptidase C14A family.
Family:
  • Belongs to the peptidase C14A family.
genes like me logo Genes that share domains with CASP12: view

Function for CASP12 Gene

Molecular function for CASP12 Gene

UniProtKB/Swiss-Prot Function:
Has no protease activity. May reduce cytokine release in response to bacterial lipopolysaccharide during infections. Reduces activation of NF-kappa-B in response to TNF.

Enzyme Numbers (IUBMB) for CASP12 Gene

Phenotypes From GWAS Catalog for CASP12 Gene

Gene Ontology (GO) - Molecular Function for CASP12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004197 cysteine-type endopeptidase activity IEA,IBA 21873635
GO:0008234 cysteine-type peptidase activity IEA --
GO:0097153 NOT cysteine-type endopeptidase activity involved in apoptotic process IBA, IKR 12054529
GO:0097199 cysteine-type endopeptidase activity involved in apoptotic signaling pathway IBA 21873635
GO:0097200 cysteine-type endopeptidase activity involved in execution phase of apoptosis IBA 21873635
genes like me logo Genes that share ontologies with CASP12: view

No data available for Phenotypes , Human Phenotype Ontology , Animal Models , miRNA , Transcription Factor Targets and HOMER Transcription for CASP12 Gene

Localization for CASP12 Gene

Gene Ontology (GO) - Cellular Components for CASP12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0005783 endoplasmic reticulum IDA 10638761
GO:0072557 IPAF inflammasome complex IBA 21873635
GO:0072559 NLRP3 inflammasome complex IBA 21873635
GO:0097169 AIM2 inflammasome complex IBA 21873635
genes like me logo Genes that share ontologies with CASP12: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot , Subcellular locations from COMPARTMENTS and Subcellular locations from the Human Protein Atlas (HPA) for CASP12 Gene

Pathways & Interactions for CASP12 Gene

genes like me logo Genes that share pathways with CASP12: view

Pathways by source for CASP12 Gene

1 Qiagen pathway for CASP12 Gene
  • Mitochondrial Apoptosis
2 GeneTex pathways for CASP12 Gene

Interacting Proteins for CASP12 Gene

SIGNOR curated interactions for CASP12 Gene

Activates:

Gene Ontology (GO) - Biological Process for CASP12 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006508 proteolysis IEA --
GO:0006915 NOT apoptotic process IBA 21873635
GO:0006919 NOT activation of cysteine-type endopeptidase activity involved in apoptotic process IBA 21873635
GO:0042981 regulation of apoptotic process IEA --
GO:0050727 regulation of inflammatory response IBA 21873635
genes like me logo Genes that share ontologies with CASP12: view

Drugs & Compounds for CASP12 Gene

(3) Drugs for CASP12 Gene - From: Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cisplatin Approved Pharma Inhibits DNA synthesis,chemotherapy drug, Potent pro-apoptotic anticancer agent; activates caspase-3, Platinum 3412
Apoptosis Activator 2 Pharma Indoledione caspase activator, cell-permeable, Promotes apoptosome formation and activates caspase-9/caspase-3 pathway. Selectively induces tumor cell apoptosis 0
PETCM Pharma Activator Caspase-3 activator, Activator of caspase-3 0

(1) Additional Compounds for CASP12 Gene - From: Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
PAC 1
315183-21-2

(4) Tocris Compounds for CASP12 Gene

Compound Action Cas Number
Apoptosis Activator 2 Promotes apoptosome formation and activates caspase-9/caspase-3 pathway. Selectively induces tumor cell apoptosis 79183-19-0
Cisplatin Potent pro-apoptotic anticancer agent; activates caspase-3 15663-27-1
PAC 1 Activator of procaspase-3; pro-apoptotic 315183-21-2
PETCM Activator of caspase-3 10129-56-3
genes like me logo Genes that share compounds with CASP12: view

Transcripts for CASP12 Gene

mRNA/cDNA for CASP12 Gene

1 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
12 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Alternative Splicing Database (ASD) splice patterns (SP) for CASP12 Gene

No ASD Table

Relevant External Links for CASP12 Gene

GeneLoc Exon Structure for
CASP12

Expression for CASP12 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CASP12 Gene

mRNA differential expression in normal tissues according to GTEx for CASP12 Gene

This gene is overexpressed in Ovary (x4.4).

Protein differential expression in normal tissues from HIPED for CASP12 Gene

This gene is overexpressed in Lung (29.1), Breast (24.4), and Bone (6.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for CASP12 Gene



Protein tissue co-expression partners for CASP12 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CASP12

SOURCE GeneReport for Unigene cluster for CASP12 Gene:

Hs.476989

mRNA Expression by UniProt/SwissProt for CASP12 Gene:

Q6UXS9-CASPC_HUMAN
Tissue specificity: Detected in heart, kidney, liver, lung, pancreas, small intestine, spleen, stomach, thymus and testis.
genes like me logo Genes that share expression patterns with CASP12: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Evidence on tissue expression from TISSUES and Phenotype-based relationships between genes and organs from Gene ORGANizer for CASP12 Gene

Orthologs for CASP12 Gene

This gene was present in the common ancestor of animals.

Orthologs for CASP12 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CASP12 31
  • 97 (a)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 50 (a)
OneToMany
-- 31
  • 39 (a)
OneToMany
-- 31
  • 36 (a)
OneToMany
-- 31
  • 35 (a)
OneToMany
Mouse
(Mus musculus)
Mammalia Casp12 31
  • 48 (a)
OneToOne
Dog
(Canis familiaris)
Mammalia CASP12 31
  • 40 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 36 (a)
OneToMany
Chicken
(Gallus gallus)
Aves -- 31
  • 40 (a)
OneToMany
Lizard
(Anolis carolinensis)
Reptilia -- 31
  • 40 (a)
OneToMany
Zebrafish
(Danio rerio)
Actinopterygii si:ch211-233g6.8 31
  • 25 (a)
ManyToMany
Fruit Fly
(Drosophila melanogaster)
Insecta Nc 31
  • 13 (a)
ManyToMany
Dredd 31
  • 10 (a)
ManyToMany
Species where no ortholog for CASP12 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • Cow (Bos Taurus)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rat (Rattus norvegicus)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for CASP12 Gene

ENSEMBL:
Gene Tree for CASP12 (if available)
TreeFam:
Gene Tree for CASP12 (if available)

Paralogs for CASP12 Gene

(6) SIMAP similar genes for CASP12 Gene using alignment to 7 proteins:

  • CASPC_HUMAN
  • D6RAQ6_HUMAN
  • D6RBW4_HUMAN
  • D6RC33_HUMAN
  • D6RG27_HUMAN
  • D6RIR9_HUMAN
  • D6RJG1_HUMAN
genes like me logo Genes that share paralogs with CASP12: view

Variants for CASP12 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for CASP12 Gene

CASPC_HUMAN-Q6UXS9
The most frequent variant has a stop codon instead of Arg-125, giving rise to truncated forms of isoform 1 (named delta, epsilon, eta, gamma) and isoform 3 (iota, teta). The variant Arg-125 (Csp12-L) is rare, except in some populations from sub-Saharan Africa. Csp12-L may increase the susceptibility to severe sepsis, and may also increase the mortality rate in sepsis patients.

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CASP12 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
rs497116 Likely Benign: Sepsis, susceptibility to; not specified 104,892,390(-) A/. NON_CODING_TRANSCRIPT_VARIANT,NO_SEQUENCE_ALTERATION
rs513131 Benign: not specified 104,890,373(-) C/.
rs647039 - p.Ser238Gly
rs693001 - p.Ile68Thr

Structural Variations from Database of Genomic Variants (DGV) for CASP12 Gene

Variant ID Type Subtype PubMed ID
dgv413e212 CNV loss 25503493
esv2656719 CNV deletion 23128226
esv2750978 CNV gain 17911159
esv2759862 CNV loss 17122850
esv27913 CNV loss 19812545
esv3429799 CNV insertion 20981092
esv3627598 CNV loss 21293372
esv3627599 CNV loss 21293372
nsv1038877 CNV gain 25217958
nsv1040536 CNV loss 25217958
nsv1040784 CNV loss 25217958
nsv1046098 CNV loss 25217958
nsv1052674 CNV loss 25217958
nsv1054456 CNV loss 25217958
nsv556217 CNV loss 21841781
nsv826072 CNV loss 20364138
nsv832255 CNV loss 17160897
nsv8869 CNV gain+loss 18304495

Variation tolerance for CASP12 Gene

Gene Damage Index Score: 3.31; 53.32% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CASP12 Gene

Human Gene Mutation Database (HGMD)
CASP12
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CASP12

No data available for Additional dbSNP identifiers (rs#s) for CASP12 Gene

Disorders for CASP12 Gene

Additional Disease Information for CASP12

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform

No disorders were found for CASP12 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for CASP12 Gene

Publications for CASP12 Gene

  1. Population distribution of the functional caspase-12 allele. (PMID: 16917906) Kachapati K … Dean M (Human mutation 2006) 2 3 4 41
  2. Spread of an inactive form of caspase-12 in humans is due to recent positive selection. (PMID: 16532395) Xue Y … Tyler-Smith C (American journal of human genetics 2006) 2 3 4
  3. Human caspase 12 has acquired deleterious mutations. (PMID: 12054529) Fischer H … Tschachler E (Biochemical and biophysical research communications 2002) 2 3 4
  4. Examination of association with candidate genes for diabetic nephropathy in a Mexican American population. (PMID: 20299368) Kim S … Adler SG (Clinical journal of the American Society of Nephrology : CJASN 2010) 3 41
  5. Persistence of full-length caspase-12 and its relation to malaria in West and Central African populations. (PMID: 20423816) McCall MB … Netea MG (European cytokine network 2010) 3 41

Products for CASP12 Gene

Sources for CASP12 Gene