NLRP4 NLR family pyrin domain containing 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NLRP4provided by HGNC
Official Full Name: NLR family pyrin domain containing 4provided by HGNC
Primary source: HGNC:HGNC:22943
See related: Ensembl:ENSG00000160505 MIM:609645; AllianceGenome:HGNC:22943
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: CT58; PAN2; RNH2; NALP4; PYPAF4; CLR19.5
Summary: The protein encoded by this gene is a member of the nucleotide-binding and leucine-rich repeat receptor (NLR) family, and is predicted to contain an N-terminal pyrin effector domain (PYD), a centrally-located nucleotide-binding and oligomerization domain (NACHT) and C-terminal leucine-rich repeats (LRR). This gene product has a demonstrated role as a negative regulator of autophagy and type I interferon signaling pathways as a result of protein interactions with its NACHT domain. The PYD domain has also been shown to be important in the inhibition of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells). [provided by RefSeq, Dec 2016]
Expression: Biased expression in testis (RPKM 3.5), lymph node (RPKM 0.8) and 1 other tissue See more
Orthologs: all
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Genomic context

Location:: 19q13.43

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (55836540..55881855)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (58935886..58981193)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (56347906..56393221)

Chromosome 19 - NC_000019.10 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 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?

The hyper-expression of NLRP4 characterizes the occurrence of macrophage activation syndrome assessing STING pathway in adult-onset Still's disease.
Title: The hyper-expression of NLRP4 characterizes the occurrence of macrophage activation syndrome assessing STING pathway in adult-onset Still's disease.
NLRP4 negatively regulates type I interferon response and influences the outcome in anti-programmed cell death protein (PD)-1/PD-ligand 1 therapy.
Title: NLRP4 negatively regulates type I interferon response and influences the outcome in anti-programmed cell death protein (PD)-1/PD-ligand 1 therapy.
Somatic Mutation of NLRP Genes in Gastric and Colonic Cancers.
Title: Somatic Mutation of NLRP Genes in Gastric and Colonic Cancers.
NLRP4 binds ARHGDIA (Rho GDP dissociation inhibitor alpha) to regulate Rho GTPase signaling and facilitate actin-mediated xenophagy.
Title: The intracellular microbial sensor NLRP4 directs Rho-actin signaling to facilitate Group A Streptococcus-containing autophagosome-like vacuole formation.
The minor allele of rs16986718G > A in NLRP4 may be a genetic marker that predicts asthma exacerbation in adult asthmatics who smoke.
Title: Association of Genetic Variants of NLRP4 with Exacerbation of Asthma: The Effect of Smoking.
NLRP4 is an important mediator of cardiac remodeling in vitro and in vivo.
Title: NLRP4 is an essential negative regulator of fructose-induced cardiac injury in vitro and in vivo.
This study describes conformational stability of native NLRP14 and mutants in their monomeric and dimeric states and compares them to NLRP4, a representative of a native pyrin domain fold.
Title: Intrinsic flexibility of NLRP pyrin domains is a key factor in their conformational dynamics, fold stability, and dimerization.
Findings suggest that NLR family pyrin domain containing 2 (NLRP2P) is a processed pseudogene that regulates NF-kappaB RelA/p65 activity and thus represents the newest member of the POP family, pyrin-only protein 4 (POP4; NLRP4).
Title: The CLRX.1/NOD24 (NLRP2P) pseudogene codes a functional negative regulator of NF-κB, pyrin-only protein 4.
Structural and functional analysis of the NLRP4 pyrin domain.
Title: Structural and functional analysis of the NLRP4 pyrin domain.
Our results provide molecular insight into the mechanisms by which NLRP4-DTX4 targets TBK1 for degradation.
Title: NLRP4 negatively regulates type I interferon signaling by targeting the kinase TBK1 for degradation via the ubiquitin ligase DTX4.

Submit: New GeneRIF Correction See all GeneRIFs (12)

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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G31875 (e-PCR)
- UniSTS:75905

RH92203 (e-PCR)
- UniSTS:85651

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables molecular adaptor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of inflammatory response	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info

General protein information

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Preferred Names: NACHT, LRR and PYD domains-containing protein 4

Names: NACHT, leucine rich repeat and PYD containing 4; PAAD and NACHT-containing protein 2; PYRIN and NACHT-containing protein 2; PYRIN-containing APAF1-like protein 4; cancer/testis antigen 58; nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 4; ribonuclease inhibitor 2

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_052802.1 RefSeqGene

Range

4963..50278

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_134444.5 → NP_604393.2 NACHT, LRR and PYD domains-containing protein 4

See identical proteins and their annotated locations for NP_604393.2

Status: REVIEWED

Source sequence(s)

AC012310, AF479747, AK315003, BE302040, BU632773

Consensus CDS

CCDS12936.1

UniProtKB/Swiss-Prot

Q86W87, Q96AY6, Q96MN2

UniProtKB/TrEMBL

B2RCA1

Related

ENSP00000301295.4, ENST00000301295.11

Conserved Domains (7) summary

smart00382
Location:147 → 279

AAA; ATPases associated with a variety of cellular activities

cd00116
Location:724 → 957

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

Pyrin_NALPs; Pyrin death domain found in NALP proteins

sd00033
Location:640 → 668

LRR_RI; leucine-rich repeat [structural motif]

sd00034
Location:895 → 922

LRR_AMN1; leucine-rich repeat [structural motif]

pfam05729
Location:149 → 318

NACHT; NACHT domain

cl00416
Location:512 → 570

CS_ACL-C_CCL; Citrate synthase (CS), citryl-CoA lyase (CCL), the C-terminal portion of the single-subunit type ATP-citrate lyase (ACL) and the C-terminal portion of the large subunit of the two-subunit type ACL. CS catalyzes the condensation of acetyl coenzyme A ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

55836540..55881855

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017026345.1 → XP_016881834.1 NACHT, LRR and PYD domains-containing protein 4 isoform X2

UniProtKB/TrEMBL

B2RCA1
XM_017026344.1 → XP_016881833.1 NACHT, LRR and PYD domains-containing protein 4 isoform X1

UniProtKB/TrEMBL

B2RCA1

Alternate T2T-CHM13v2.0

Genomic

NC_060943.1 Alternate T2T-CHM13v2.0

Range

58935886..58981193

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054319921.1 → XP_054175896.1 NACHT, LRR and PYD domains-containing protein 4 isoform X2
XM_054319920.1 → XP_054175895.1 NACHT, LRR and PYD domains-containing protein 4 isoform X1