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

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: mouse all
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Genomic context

Location:: 2p22.3

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (32224449..32265743, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (32272955..32314278, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (32449518..32490812, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

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?

Three cases of autoinflammatory disease with novel NLRC4 mutations, and the first mutation reported in the CARD domain of NLRC4 associated with autoinflammatory infantile enterocolitis (AIFEC).
Title: Three cases of autoinflammatory disease with novel NLRC4 mutations, and the first mutation reported in the CARD domain of NLRC4 associated with autoinflammatory infantile enterocolitis (AIFEC).
Human NLRC4 expression promotes cancer survival and associates with type I interferon signaling and immune infiltration.
Title: Human NLRC4 expression promotes cancer survival and associates with type I interferon signaling and immune infiltration.
NLRC4-mediated pyroptosis was involved in coagulation disorders of acute pancreatitis.
Title: NLRC4-mediated pyroptosis was involved in coagulation disorders of acute pancreatitis.
NFkappaB and NLRP3/NLRC4 inflammasomes regulate differentiation, activation and functional properties of monocytes in response to distinct SARS-CoV-2 proteins.
Title: NFκB and NLRP3/NLRC4 inflammasomes regulate differentiation, activation and functional properties of monocytes in response to distinct SARS-CoV-2 proteins.
[Expressions of NLRP1 and NLRC4 inflammasomes in prostate cancer and their clinical value].
Title: [Expressions of NLRP1 and NLRC4 inflammasomes in prostate cancer and their clinical value].
NLRC4 gain-of-function variant is identified in a patient with systemic lupus erythematosus.
Title: NLRC4 gain-of-function variant is identified in a patient with systemic lupus erythematosus.
Targeting Desulfovibrio vulgaris flagellin-induced NAIP/NLRC4 inflammasome activation in macrophages attenuates ulcerative colitis.
Title: Targeting Desulfovibrio vulgaris flagellin-induced NAIP/NLRC4 inflammasome activation in macrophages attenuates ulcerative colitis.
Early-onset recurrent panniculitis as a phenotype of NLRC4-associated autoinflammatory syndrome: Characterization of pathogenicity of the p.Ser445Pro NLRC4 variant.
Title: Early-onset recurrent panniculitis as a phenotype of NLRC4-associated autoinflammatory syndrome: Characterization of pathogenicity of the p.Ser445Pro NLRC4 variant.
Ribosome-rescuer PELO catalyzes the oligomeric assembly of NOD-like receptor family proteins via activating their ATPase enzymatic activity.
Title: Ribosome-rescuer PELO catalyzes the oligomeric assembly of NOD-like receptor family proteins via activating their ATPase enzymatic activity.
LNCGM1082-mediated NLRC4 activation drives resistance to bacterial infection.
Title: LNCGM1082-mediated NLRC4 activation drives resistance to bacterial infection.

Submit: New GeneRIF Correction See all GeneRIFs (65)

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

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 EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH103483 (e-PCR)
- UniSTS:97808

RH119418 (e-PCR)
- UniSTS:132960

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 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 pyroptotic inflammatory response	ISS Inferred from Sequence or Structural Similarity more info
involved_in pyroptotic inflammatory response	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

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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)

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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_041780.1 RefSeqGene

Range

5858..46291

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1317

mRNA and Protein(s)

NM_001199138.2 → NP_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:738 → 978

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:738 → 764

LRR_RI; leucine-rich repeat [structural motif]

sd00034
Location:691 → 713

LRR_AMN1; leucine-rich repeat [structural motif]

pfam00619
Location:1 → 87

CARD; Caspase recruitment domain

pfam05729
Location:163 → 316

NACHT; NACHT domain
NM_001199139.1 → NP_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:738 → 978

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:738 → 764

LRR_RI; leucine-rich repeat [structural motif]

sd00034
Location:691 → 713

LRR_AMN1; leucine-rich repeat [structural motif]

pfam00619
Location:1 → 87

CARD; Caspase recruitment domain

pfam05729
Location:163 → 316

NACHT; NACHT domain
NM_001302504.1 → NP_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:79 → 329

LRR; Leucine-rich repeat (LRR) protein [Transcription]

cd00116
Location:71 → 313

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:100 → 124

LRR_RI; leucine-rich repeat [structural motif]

pfam00619
Location:1 → 87

CARD; Caspase recruitment domain
NM_021209.4 → NP_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:738 → 978

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:738 → 764

LRR_RI; leucine-rich repeat [structural motif]

sd00034
Location:691 → 713

LRR_AMN1; leucine-rich repeat [structural motif]

pfam00619
Location:1 → 87

CARD; Caspase recruitment domain

pfam05729
Location:163 → 316

NACHT; NACHT domain