NLRP6

NLR family pyrin domain containing 6, the group of Pyrin domain containing|NLR family

Basic information

Region (hg38): 11:278407-285388

Previous symbols: [ "NALP6" ]

Links

ENSG00000174885 ∙ NCBI:171389 ∙ OMIM:609650 ∙ HGNC:22944 ∙ Uniprot:P59044 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NLRP6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NLRP6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			78	9	1	88
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	78	9	2

Variants in NLRP6

This is a list of pathogenic ClinVar variants found in the NLRP6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-278589-C-T		not specified	Uncertain significance (Jun 13, 2023)
11-278820-A-G			not provided (-)
11-278848-G-A			not provided (-)
11-278992-G-A			not provided (-)
11-279056-C-G			not provided (-)
11-279242-G-A			not provided (-)
11-279307-C-G			not provided (-)
11-279335-C-G		not specified	Uncertain significance (Aug 17, 2022)
11-279343-G-A		not specified	Uncertain significance (Jan 01, 2025)
11-279352-C-G		not specified	Uncertain significance (May 12, 2024)
11-279434-C-T		not specified	Likely benign (Dec 12, 2023)
11-279466-G-A		not specified	Uncertain significance (May 21, 2024)
11-279481-G-A			not provided (-)
11-279558-G-A			not provided (-)
11-279592-G-A		not specified	Uncertain significance (Feb 02, 2022)
11-279792-G-C			not provided (-)
11-279808-G-T			not provided (-)
11-279819-C-A			not provided (-)
11-279834-G-T		not specified	Uncertain significance (Jun 22, 2021)
11-279975-G-A			not provided (-)
11-280126-C-T		not specified	Uncertain significance (Mar 28, 2024)
11-280173-T-C		not specified	Uncertain significance (Nov 28, 2024)
11-280197-G-A		not specified	Uncertain significance (Aug 26, 2024)
11-280248-G-C		not specified	Uncertain significance (Mar 14, 2025)
11-280264-C-T		not specified	Uncertain significance (Nov 15, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NLRP6	protein_coding	protein_coding	ENST00000312165	8	6995

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000274	0.999	125667	0	79	125746	0.000314

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.76	393	504	0.779	0.0000328	5566
Missense in Polyphen		88	134.52	0.65417		1815
Synonymous	1.24	218	243	0.899	0.0000168	1938
Loss of Function	2.99	11	28.1	0.391	0.00000153	314

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000617	0.000608
Ashkenazi Jewish	0.0000996	0.0000992
East Asian	0.0000551	0.0000544
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000483	0.000475
Middle Eastern	0.0000551	0.0000544
South Asian	0.000175	0.000163
Other	0.000493	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As the sensor component of the NLRP6 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP6, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1- catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. The precise NLRP6 activation stimulus has not been identified yet (By similarity) (PubMed:12387869). Essential for gut mucosal self-renewal and proliferation. Maintains intestinal homeostasis and a healthy intestinal microbiota. This function is, at least partially, mediated by IL18, and not IL1B, produced by nonhematopoietic cells. Influences intestinal barrier function and microbial homeostasis through the regulation of goblet cell mucus secretion. Acts by promoting autophagy in goblet cells, an essential step for mucus granule exocytosis. Its role in goblet cell physiology is inflammasome- dependent, but IL1B- and IL18-independent. During systemic bacterial infections, may negatively regulate inflammatory signaling and inhibit the influx of monocytes and neutrophils to the circulation and to the peritoneum. May promote peripheral nerve recovery following injury via an inflammasome-independent mechanism (By similarity). {ECO:0000250|UniProtKB:Q91WS2, ECO:0000250|UniProtKB:Q96P20, ECO:0000269|PubMed:12387869}.
• Pathway: NOD-like receptor signaling pathway - Homo sapiens (human) (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.530
• rvis_EVS: 1.27
• rvis_percentile_EVS: 93.65

Haploinsufficiency Scores

• pHI: 0.133
• hipred: Y
• hipred_score: 0.728
• ghis: 0.409

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.377

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nlrp6
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); neoplasm; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: negative regulation of inflammatory response to antigenic stimulus;inflammatory response;G protein-coupled receptor signaling pathway;response to bacterium;regulation of autophagy;negative regulation of toll-like receptor signaling pathway;wound healing;negative regulation of I-kappaB kinase/NF-kappaB signaling;innate immune response;regulation of inflammatory response;regulation of mucus secretion;negative regulation of ERK1 and ERK2 cascade
• Cellular component: plasma membrane;nuclear membrane;inflammasome complex
• Molecular function: vasopressin receptor activity;ATP binding