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    NLRC4 NLR family CARD domain containing 4 [ Homo sapiens (human) ]

    Gene ID: 58484, updated on 18-Dec-2023

    Summary

    Official Symbol
    NLRC4provided by HGNC
    Official Full Name
    NLR family CARD domain containing 4provided by HGNC
    Primary source
    HGNC:HGNC:16412
    See related
    Ensembl:ENSG00000091106 MIM:606831; AllianceGenome:HGNC:16412
    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
    CLAN; IPAF; AIFEC; CLAN1; CLANA; CLANB; CLANC; CLAND; FCAS4; CARD12; CLR2.1
    Summary
    This gene encodes a member of the caspase recruitment domain-containing NLR family. Family members play essential roles in innate immune response to a wide range of pathogenic organisms, tissue damage and other cellular stresses. Mutations in this gene result in autoinflammation with infantile enterocolitis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]
    Expression
    Broad expression in appendix (RPKM 5.7), bone marrow (RPKM 3.2) and 17 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See NLRC4 in Genome Data Viewer
    Location:
    2p22.3
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (32224449..32265743, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (32272955..32314278, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (32449518..32490812, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene solute carrier family 30 member 6 Neighboring gene DEAD-box helicase 50 pseudogene 1 Neighboring gene RNA, U6 small nuclear 647, pseudogene Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:32502088-32502833 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11340 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:32518022-32518694 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:32521211-32521404 Neighboring gene Yip1 domain family member 4 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:32581762-32582274 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11342 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:32582789-32583301 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:32586084-32586282 Neighboring gene baculoviral IAP repeat containing 6 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:32662063-32662288 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:32672333-32672910 Neighboring gene microRNA 558

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Familial cold autoinflammatory syndrome 4
    MedGen: C4015276 OMIM: 616115 GeneReviews: Not available
    Compare labs
    Periodic fever-infantile enterocolitis-autoinflammatory syndrome
    MedGen: C4015067 OMIM: 616050 GeneReviews: Not available
    Compare labs

    EBI GWAS Catalog

    Description
    Novel gene variants predict serum levels of the cytokines IL-18 and IL-1ra in older adults.
    EBI GWAS Catalog

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables caspase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables endopeptidase activator activity IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables magnesium ion binding TAS
    Traceable Author Statement
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in activation of cysteine-type endopeptidase activity IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in activation of cysteine-type endopeptidase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in activation of innate immune response ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in defense response to bacterium IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in defense response to bacterium IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in detection of bacterium IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in detection of bacterium IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in icosanoid biosynthetic process NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in inflammatory response ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in innate immune response IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in pattern recognition receptor signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of NF-kappaB transcription factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of inflammatory response NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of interleukin-1 beta production IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in positive regulation of interleukin-1 beta production NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of protein processing IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in protein homooligomerization ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in pyroptosis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in pyroptosis NAS
    Non-traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    part_of IPAF inflammasome complex ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    part_of canonical inflammasome complex NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in cytoplasm NAS
    Non-traceable Author Statement
    more info
    PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    located_in cytosol ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
     
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
     

    General protein information

    Preferred Names
    NLR family CARD domain-containing protein 4
    Names
    CARD, LRR, and NACHT-containing protein
    CED-4-like protein Clan
    ICE-protease activating factor
    NOD-like receptor C4
    caspase recruitment domain family, member 12
    caspase recruitment domain-containing protein 12
    nucleotide-binding oligomerization domain, leucine rich repeat and CARD domain containing 4

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_041780.1 RefSeqGene

      Range
      5858..46291
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1317

    mRNA and Protein(s)

    1. NM_001199138.2NP_001186067.1  NLR family CARD domain-containing protein 4 isoform a

      See identical proteins and their annotated locations for NP_001186067.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has an alternate 5' UTR exon and encodes the same protein, as compared to variant 1.
      Source sequence(s)
      AK095467, AL121653, BC031555
      Consensus CDS
      CCDS33174.1
      UniProtKB/Swiss-Prot
      A8K9F8, B2RBQ3, B3KTF0, D6W580, Q96J81, Q96J82, Q96J83, Q9NPP4
      Related
      ENSP00000385428.1, ENST00000402280.6
      Conserved Domains (5) summary
      cd00116
      Location:738978
      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 ...
      sd00033
      Location:738764
      LRR_RI; leucine-rich repeat [structural motif]
      sd00034
      Location:691713
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam00619
      Location:187
      CARD; Caspase recruitment domain
      pfam05729
      Location:163316
      NACHT; NACHT domain
    2. NM_001199139.1NP_001186068.1  NLR family CARD domain-containing protein 4 isoform a

      See identical proteins and their annotated locations for NP_001186068.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has an alternate splice site in the 5' UTR and encodes the same protein, as compared to variant 1.
      Source sequence(s)
      AW337918, AY035391
      Consensus CDS
      CCDS33174.1
      UniProtKB/Swiss-Prot
      A8K9F8, B2RBQ3, B3KTF0, D6W580, Q96J81, Q96J82, Q96J83, Q9NPP4
      Conserved Domains (5) summary
      cd00116
      Location:738978
      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 ...
      sd00033
      Location:738764
      LRR_RI; leucine-rich repeat [structural motif]
      sd00034
      Location:691713
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam00619
      Location:187
      CARD; Caspase recruitment domain
      pfam05729
      Location:163316
      NACHT; NACHT domain
    3. NM_001302504.1NP_001289433.1  NLR family CARD domain-containing protein 4 isoform b

      See identical proteins and their annotated locations for NP_001289433.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an alternate in-frame exon in the 5' coding region compared to variant 1. It encodes isoform b, which is shorter than isoform a.
      Source sequence(s)
      AL121653, AW337918, AY027788
      Consensus CDS
      CCDS77400.1
      UniProtKB/Swiss-Prot
      Q9NPP4
      Related
      ENSP00000339666.6, ENST00000342905.10
      Conserved Domains (4) summary
      COG4886
      Location:79329
      LRR; Leucine-rich repeat (LRR) protein [Transcription]
      cd00116
      Location:71313
      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 ...
      sd00033
      Location:100124
      LRR_RI; leucine-rich repeat [structural motif]
      pfam00619
      Location:187
      CARD; Caspase recruitment domain
    4. NM_021209.4NP_067032.3  NLR family CARD domain-containing protein 4 isoform a

      See identical proteins and their annotated locations for NP_067032.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      AW337918, BC031555, DN998613
      Consensus CDS
      CCDS33174.1
      UniProtKB/Swiss-Prot
      A8K9F8, B2RBQ3, B3KTF0, D6W580, Q96J81, Q96J82, Q96J83, Q9NPP4
      Related
      ENSP00000354159.5, ENST00000360906.9
      Conserved Domains (5) summary
      cd00116
      Location:738978
      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 ...
      sd00033
      Location:738764
      LRR_RI; leucine-rich repeat [structural motif]
      sd00034
      Location:691713
      LRR_AMN1; leucine-rich repeat [structural motif]
      pfam00619
      Location:187
      CARD; Caspase recruitment domain
      pfam05729
      Location:163316
      NACHT; NACHT domain

    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

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      32224449..32265743 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047445356.1XP_047301312.1  NLR family CARD domain-containing protein 4 isoform X1

      UniProtKB/TrEMBL
      A0A499FIV7
      Related
      ENSP00000385090.3, ENST00000404025.3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      32272955..32314278 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054343247.1XP_054199222.1  NLR family CARD domain-containing protein 4 isoform X1

      UniProtKB/TrEMBL
      A0A499FIV7