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

Gene ID: 58484, updated on 17-Jun-2019

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
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

Genomic context

See NLRC4 in Genome Data Viewer
Location:
2p22.3
Exon count:
11
Annotation release Status Assembly Chr Location
109.20190607 current GRCh38.p13 (GCF_000001405.39) 2 NC_000002.12 (32224449..32265743, complement)
105 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 Yip1 domain family member 4 Neighboring gene baculoviral IAP repeat containing 6 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 FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

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

NHGRI GWAS Catalog

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

Pathways from BioSystems

  • Direct p53 effectors, organism-specific biosystem (from Pathway Interaction Database)
    Direct p53 effectors, organism-specific biosystem
    Direct p53 effectors
  • Gene Expression, organism-specific biosystem (from REACTOME)
    Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
  • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
    Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Inflammasomes, organism-specific biosystem (from REACTOME)
    Inflammasomes, organism-specific biosystemIn contrast to NOD1/2 some NLRPs function as large macromolecular complexes called 'Inflammasomes'. These multiprotein platforms control activation of the cysteinyl aspartate protease caspase-1 and t...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Legionellosis, organism-specific biosystem (from KEGG)
    Legionellosis, organism-specific biosystemLegionellosis is a potentially fatal infectious disease caused by the bacterium Legionella pneumophila and other legionella species. Two distinct clinical and epidemiological syndromes are associated...
  • Legionellosis, conserved biosystem (from KEGG)
    Legionellosis, conserved biosystemLegionellosis is a potentially fatal infectious disease caused by the bacterium Legionella pneumophila and other legionella species. Two distinct clinical and epidemiological syndromes are associated...
  • NOD-like receptor signaling pathway, organism-specific biosystem (from KEGG)
    NOD-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains mo...
  • NOD-like receptor signaling pathway, conserved biosystem (from KEGG)
    NOD-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains mo...
  • Nucleotide-binding Oligomerization Domain (NOD) pathway, organism-specific biosystem (from WikiPathways)
    Nucleotide-binding Oligomerization Domain (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...
  • Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways, organism-specific biosystem (from REACTOME)
    Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways, organism-specific biosystemThe innate immune system is the first line of defense against invading microorganisms, a broad specificity response characterized by the recruitment and activation of phagocytes and the release of an...
  • Salmonella infection, organism-specific biosystem (from KEGG)
    Salmonella infection, organism-specific biosystemSalmonella infection usually presents as a self-limiting gastroenteritis or the more severe typhoid fever and bacteremia. The common disease-causing Salmonella species in human is a single species, S...
  • Salmonella infection, conserved biosystem (from KEGG)
    Salmonella infection, conserved biosystemSalmonella infection usually presents as a self-limiting gastroenteritis or the more severe typhoid fever and bacteremia. The common disease-causing Salmonella species in human is a single species, S...
  • TP53 Regulates Transcription of Caspase Activators and Caspases, organism-specific biosystem (from REACTOME)
    TP53 Regulates Transcription of Caspase Activators and Caspases, organism-specific biosystemTP53 (p53) transcriptionally regulates cytosolic caspase activators, such as APAF1, PIDD1, and NLRC4, and caspases themselves, such as CASP1, CASP6 and CASP10. These caspases and their activators are...
  • TP53 Regulates Transcription of Cell Death Genes, organism-specific biosystem (from REACTOME)
    TP53 Regulates Transcription of Cell Death Genes, organism-specific biosystemThe tumor suppressor TP53 (p53) exerts its tumor suppressive role in part by regulating transcription of a number of genes involved in cell death, mainly apoptotic cell death. The majority of apoptot...
  • The IPAF inflammasome, organism-specific biosystem (from REACTOME)
    The IPAF inflammasome, organism-specific biosystemThe IPAF (NLRC4) inflammasome can be activated by several stimuli, most notably by Gram-negative bacteria with either type III or type IV secretion systems that result in cytosolic flagellin, which i...
  • Transcriptional Regulation by TP53, organism-specific biosystem (from REACTOME)
    Transcriptional Regulation by TP53, organism-specific biosystemThe tumor suppressor TP53 (encoded by the gene p53) is a transcription factor. Under stress conditions, it recognizes specific responsive DNA elements and thus regulates the transcription of many gen...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IDA
Inferred from Direct Assay
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
magnesium ion binding TAS
Traceable Author Statement
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
activation of cysteine-type endopeptidase activity involved in apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
activation of innate immune response ISS
Inferred from Sequence or Structural Similarity
more info
 
apoptotic process IEA
Inferred from Electronic Annotation
more info
 
defense response to bacterium IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
defense response to bacterium IDA
Inferred from Direct Assay
more info
PubMed 
detection of bacterium IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
detection of bacterium IDA
Inferred from Direct Assay
more info
PubMed 
inflammatory response ISS
Inferred from Sequence or Structural Similarity
more info
 
innate immune response IEA
Inferred from Electronic Annotation
more info
 
interleukin-1 beta secretion IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
interleukin-1 beta secretion IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
protein homooligomerization ISS
Inferred from Sequence or Structural Similarity
more info
 
pyroptosis ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of apoptotic process TAS
Traceable Author Statement
more info
 
Component Evidence Code Pubs
IPAF inflammasome complex ISS
Inferred from Sequence or Structural Similarity
more info
 
cytosol ISS
Inferred from Sequence or Structural Similarity
more info
 
cytosol TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
NLR family CARD domain-containing protein 4
Names
CARD, LRR, and NACHT-containing protein
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)

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
    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
    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
    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: Homo sapiens Annotation Release 109

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p13 Primary Assembly

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

mRNA and Protein(s)

  1. XM_017004619.1XP_016860108.1  NLR family CARD domain-containing protein 4 isoform X1

    Related
    ENSP00000385090.3, ENST00000404025.3

RNA

  1. XR_001738872.1 RNA Sequence

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