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    NLRP12 NLR family, pyrin domain containing 12 [ Homo sapiens (human) ]

    Gene ID: 91662, updated on 10-Jun-2013
    Official Symbol
    NLRP12provided by HGNC
    Official Full Name
    NLR family, pyrin domain containing 12provided by HGNC
    Primary source
    HGNC:22938
    See related
    Ensembl:ENSG00000142405; HPRD:14803; MIM:609648; Vega:OTTHUMG00000060776
    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
    RNO; PAN6; RNO2; FCAS2; NALP12; PYPAF7; CLR19.3
    Summary
    This gene encodes a member of the CATERPILLER family of cytoplasmic proteins. The encoded protein, which contains an N-terminal pyrin domain, a NACHT domain, a NACHT-associated domain, and a C-terminus leucine-rich repeat region, functions as an attenuating factor of inflammation by suppressing inflammatory responses in activated monocytes. Mutations in this gene cause familial cold autoinflammatory syndrome type 2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]
    Location :
    19q13.42
    Sequence :
    Chromosome: 19; NC_000019.9 (54296838..54327648, complement)
    See NLRP12 in Epigenomics, MapViewer

    Chromosome 19 - NC_000019.9Genomic Context describing neighboring genes Neighboring gene microRNA 372 Neighboring gene microRNA 373 Neighboring gene myeloid-associated differentiation marker Neighboring gene protein kinase C, gamma

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details

    Related articles in PubMed

    1. The rhapsody of NLRPs: master players of inflammation...and a lot more. Zambetti LP, et al. Immunol Res, 2012 Sep. PMID 22427013.
    2. The NLRP12 pyrin domain: structure, dynamics, and functional insights. Pinheiro AS, et al. J Mol Biol, 2011 Nov 4. PMID 21978668.
    3. Identification and functional consequences of a recurrent NLRP12 missense mutation in periodic fever syndromes. Jéru I, et al. Arthritis Rheum, 2011 May. PMID 21538323.
    4. Clinical presentation and pathogenesis of cold-induced autoinflammatory disease in a family with recurrence of an NLRP12 mutation. Borghini S, et al. Arthritis Rheum, 2011 Mar. PMID 21360512.
    5. Single nucleotide polymorphisms of matrix metalloproteinase 9 (MMP9) and tumor protein 73 (TP73) interact with Epstein-Barr virus in chronic lymphocytic leukemia: results from the European case-control study EpiLymph. Casabonne D, et al. Haematologica, 2011 Feb. PMID 21048031.

    See all (27) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Even with a variable range of associated manifestations, the extreme sensitivity to cold represents the main clinical hallmark in an individual carrying the p.D294E mutation of the NLRP12 gene.
      Title: Clinical presentation and pathogenesis of cold-induced autoinflammatory disease in a family with recurrence of an NLRP12 mutation.
    2. The authors report the first in vitro confirmed non-homotypic interaction between NLRP12 pyrin domain and the pro-apoptotic protein Fas-associated factor 1 (FAF-1), which links the innate immune system to apoptotic signaling.
      Title: The NLRP12 pyrin domain: structure, dynamics, and functional insights.
    3. NLRP12 missense mutation in periodic fever syndromes; study provides evidence of deleterious effect of an NLRP12 missense mutation; this newly identified molecular defect emphasizes the crucial role played by NLRP12 in autoinflammation
      Title: Identification and functional consequences of a recurrent NLRP12 missense mutation in periodic fever syndromes.
    4. Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Single nucleotide polymorphisms of matrix metalloproteinase 9 (MMP9) and tumor protein 73 (TP73) interact with Epstein-Barr virus in chronic lymphocytic leukemia: results from the European case-control study EpiLymph.
    5. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    6. Relative copy numbers for the inflammasome mRNAs for ASC, caspase-1, NALP1, and Pypaf-7 were significantly lower in patients with septic shock compared with critically ill control subjects.
      Title: Inflammasome mRNA expression in human monocytes during early septic shock.
    7. ATP binding by NLRP12 is critical for its inhibitory function.
      Title: ATP binding by monarch-1/NLRP12 is critical for its inhibitory function.
    8. Observational study of gene-disease association. (HuGE Navigator)
      Title: The genetics of NOD-like receptors in Crohn's disease.
    9. Two mutations, nonsense and splice site, were identified in NALP12 in two families with periodic fever syndromes.
      Title: Mutations in NALP12 cause hereditary periodic fever syndromes.
    10. Heat shock protein 90 is a critical regulator of Monarch-1 anti-inflammatory activity
      Title: Heat shock protein 90 associates with monarch-1 and regulates its ability to promote degradation of NF-kappaB-inducing kinase.
    Submit: New GeneRIF Correction See all (14)

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

    Review eQTL and phenotype association data in this region using PheGenI

    Products Interactant Other Gene Complex Source Pubs Description
    P59046 P51617 IRAK1    HPRD  PubMed  
    P59046 Q9ULZ3 PYCARD    HPRD  PubMed  
    BioGRID:124861 BioGRID:199230 Dlg4    BioGRID  PubMed Protein-peptide 
    BioGRID:124861 BioGRID:116298 FAF1    BioGRID  PubMed Two-hybrid 
    BioGRID:124861 BioGRID:109552 HSP90AA1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:124861 BioGRID:109540 HSPA4    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:124861 BioGRID:109544 HSPA8    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:124861 BioGRID:109863 IRAK1    BioGRID  PubMed Affinity Capture-Western 
    • NOD pathway, organism-specific biosystem (from WikiPathways)
      NOD pathway, organism-specific biosystemThe NOD (nucleotide-binding oligomerization domain) proteins NOD1 and NOD2 have important roles in innate immunity as sensors of microbial components derived from bacterial peptidoglycan. The importa...

    Markers

    Genotypes

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    cysteine-type endopeptidase activator activity involved in apoptotic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    activation of cysteine-type endopeptidase activity involved in apoptotic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    negative regulation of I-kappaB kinase/NF-kappaB cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    negative regulation of NF-kappaB transcription factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    negative regulation of Toll signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    negative regulation of cytokine secretion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    negative regulation of inflammatory response IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    negative regulation of interleukin-1 secretion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    negative regulation of interleukin-6 biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    negative regulation of protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    negative regulation of signal transduction IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    positive regulation of inflammatory response NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    positive regulation of interleukin-1 beta secretion NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    regulation of interleukin-18 biosynthetic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    release of cytoplasmic sequestered NF-kappaB IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    signal transduction NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Preferred Names
    NACHT, LRR and PYD domains-containing protein 12
    Names
    NACHT, LRR and PYD domains-containing protein 12
    monarch 1
    regulated by nitric oxide
    PYRIN-containing APAF1-like protein 7
    nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 12

    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_008651.1 RefSeqGene

      Range
      4992..35811
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001277126.1 → NP_001264055.1  NACHT, LRR and PYD domains-containing protein 12 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) represents the longest transcript and encodes the longest isoform (3).
      Source sequence(s)
      AY116204, AY154467, DA619102
      UniProtKB/Swiss-Prot
      P59046
      Conserved Domains (3) summary
      cd00116
      Location:688 – 981
      Blast Score: 362
      LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
      cd08320
      Location:11 – 92
      Blast Score: 292
      Pyrin_NALPs; Pyrin death domain found in NALP proteins
      pfam05729
      Location:212 – 381
      Blast Score: 442
      NACHT; NACHT domain

    2. NM_001277129.1 → NP_001264058.1  NACHT, LRR and PYD domains-containing protein 12 isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses an alternate in-frame splice site in the central coding region, and lacks an alternate in-frame exon in the 3' coding region, compared to variant 3. The encoded isoform (4) is shorter than isoform 3.
      Source sequence(s)
      AK095460, AY154467, BC028069, DA619102
      UniProtKB/TrEMBL
      A8MTQ2
      UniProtKB/TrEMBL
      B3KTE7
      UniProtKB/Swiss-Prot
      P59046
      Conserved Domains (3) summary
      cd00116
      Location:693 – 978
      Blast Score: 336
      LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
      cd08320
      Location:11 – 92
      Blast Score: 293
      Pyrin_NALPs; Pyrin death domain found in NALP proteins
      pfam05729
      Location:212 – 381
      Blast Score: 445
      NACHT; NACHT domain

    3. NM_144687.3 → NP_653288.1  NACHT, LRR and PYD domains-containing protein 12 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site in the central coding region, compared to variant 3, resulting in an isoform (2) that is 1 aa shorter than isoform 3.
      Source sequence(s)
      AY154467, BC028069, DA619102
      Consensus CDS
      CCDS12864.1
      UniProtKB/Swiss-Prot
      P59046
      Related
      ENSP00000319377, OTTHUMP00000067226, ENST00000324134, OTTHUMT00000134340
      Conserved Domains (4) summary
      cd00116
      Location:717 – 1035
      Blast Score: 359
      LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
      cd08320
      Location:11 – 92
      Blast Score: 292
      Pyrin_NALPs; Pyrin death domain found in NALP proteins
      pfam05729
      Location:212 – 381
      Blast Score: 443
      NACHT; NACHT domain
      cl15309
      Location:561 – 866
      Blast Score: 268
      LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

    Reference GRCh37.p10 Primary Assembly

    Genomic

    1. NC_000019.9 Reference GRCh37.p10 Primary Assembly

      Range
      54296838..54327648, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000151.1 Alternate HuRef

      Range
      50616403..50647253, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.0

    Genomic

    1. NC_018930.1 Alternate CHM1_1.0

      Range
      54457504..54488269, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_033297.2: Suppressed sequence

      Description
      NM_033297.2: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    genomic ABBA01068193.1 (2885..3782) None
    genomic ABBA01068194.1 None
    genomic ABBA01068195.1 None
    genomic ABBA01068196.1 None
    genomic ABBA01068197.1 None
    genomic ABBA01068198.1 None
    genomic ABBA01068199.1 None
    genomic ABBA01068200.1 None
    genomic AC008753.9 (62315..93126) None
    genomic AMYH01009965.1 (37578..68343) None
    genomic CH471135.1 EAW72151.1
      EAW72152.1
      EAW72153.1
      EAW72154.1
      EAW72155.1
      EAW72156.1
      EAW72157.1
    mRNA AF231021.1 AAK14942.1
    mRNA AK095460.1 BAG53059.1
    mRNA AK290772.1 BAF83461.1
    mRNA AY095146.1 AAM18227.1
    mRNA AY116204.1 AAM75142.1
    mRNA AY116205.1 AAM75143.1
    mRNA AY116206.1 AAM75144.1
    mRNA AY116207.1 AAM75145.1
    mRNA AY154467.1 AAO18163.1
    mRNA BC028069.1 AAH28069.1
    mRNA DA619102.1 None
    other-genetic DQ891084.2 ABM82010.1
    other-genetic DQ894266.2 ABM85192.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P59046.2 GenPept UniProtKB/Swiss-Prot:P59046

    Additional Links

    Gene LinkOut

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

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

      Table of contents

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        Conserved Domain Database Links between Entrez Gene and Conserved Domain Database (CDD) are calculated from the domains annotated by the CDD group on Reference Sequence proteins.
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        Links between Gene and PubMed are the result of the following: 1. Manual curation within NCBI. Part of the process of generating a REVIEWED RefSeq is an analysis of the current literature. Papers that are seminal in defining the gene, its sequence, and its function are added to the record at that time. Alert users point out gaps or errors in papers associated with a Gene record. These messages are reviewed and implemented as required. 2. Integration of information from other public databases. Gene integrates gene-citation from resources external to NCBI such as model organism-specific databases, Gene Ontology (GO), groups curating interactions, and sequence databases. The assumption in using these source is that they report citations specific to a gene in a known species. Gene does not process citations from OMIM automatically, because many of citations in OMIM refer to studies of genes in species other than human.
      • PubMed (GeneRIF)
        GeneRIF -- Gene Reference Into Function Staff of the Index Section in the National Library of Medicine review the current literature. When they find articles focused on the structure and function of a gene, they write a brief summary of the impact of the paper and make the connection between the citation (PubMed) and Gene. An interface exists for interested users to submit such data as well. http://www.ncbi.nlm.nih.gov/projects/GeneRIF/GeneRIFhelp.html
      • PubMed (OMIM)
        Links are provided when Gene has a link to a record in OMIM, and OMIM explicitly cites these publications in PubMed.
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        Citations in PubMed identified from shared sequence and PMC links.
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        Link to Protein RefSeqs
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      • UniSTS
        Related UniSTS records

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