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

Summary

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

Location:: 11q22.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (104883286..104898460, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (104887413..104902580, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (104756445..104769187, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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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

NG_028201.3 RefSeqGene

Range

4791..17743

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

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
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
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
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
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
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
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
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
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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

104883286..104898460 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 PATCHES

Genomic

NW_025791791.1 Reference GRCh38.p14 PATCHES

Range

182419..197593 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

104887413..104902580 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

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.