NLRP2

NLR family pyrin domain containing 2, the group of NLR family|Pyrin domain containing

Basic information

Region (hg38): 19:54953130-55001142

Previous symbols: [ "NALP2" ]

Links

ENSG00000022556 ∙ NCBI:55655 ∙ OMIM:609364 ∙ HGNC:22948 ∙ Uniprot:Q9NX02 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• oocyte/zygote/embryo maturation arrest 18 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Oocyte/zygote/embryo maturation arrest 18	AR	Obstetric	Some individuals have been described as able to achieve successful pregnancies using IVF	Obstetric	30877238

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NLRP2 gene.

• not_specified (172 variants)
• not_provided (114 variants)
• NLRP2-related_disorder (78 variants)
• Oocyte/zygote/embryo_maturation_arrest_18 (5 variants)
• Multisystem_inflammatory_syndrome_in_children (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NLRP2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017852.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	57	6	67
missense	1		176	39	12	228
nonsense	2	1	7			10
start loss						0
frameshift			11			11
splice donor/acceptor (+/-2bp)			3			3
Total	3	1	201	96	18

Highest pathogenic variant AF is 0.000008673886

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NLRP2	protein_coding	protein_coding	ENST00000543010	12	48013

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.42e-38	1.21e-7	125464	1	283	125748	0.00113

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.35	750	590	1.27	0.0000373	6952
Missense in Polyphen		183	161.88	1.1304		2158
Synonymous	-4.82	360	261	1.38	0.0000188	2086
Loss of Function	-1.13	53	44.8	1.18	0.00000264	505

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00232	0.00213
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000652	0.000653
Finnish	0.000647	0.000647
European (Non-Finnish)	0.00132	0.00131
Middle Eastern	0.000652	0.000653
South Asian	0.00176	0.00170
Other	0.000978	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Suppresses TNF- and CD40-induced NFKB1 activity at the level of the IKK complex, by inhibiting NFKBIA degradation induced by TNF. When associated with PYCARD, activates CASP1, leading to the secretion of mature proinflammatory cytokine IL1B. May be a component of the inflammasome, a protein complex which also includes PYCARD, CARD8 and CASP1 and whose function would be the activation of proinflammatory caspases. {ECO:0000269|PubMed:15456791}.
• Pathway: Nucleotide-binding Oligomerization Domain (NOD) pathway (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.955
• rvis_EVS: 1.2
• rvis_percentile_EVS: 92.96

Haploinsufficiency Scores

• pHI: 0.843
• hipred: N
• hipred_score: 0.112
• ghis: 0.469

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.827

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nlrp2

Gene ontology

• Biological process: apoptotic process;inflammatory response;negative regulation of NF-kappaB transcription factor activity;positive regulation of cysteine-type endopeptidase activity involved in apoptotic process;innate immune response;positive regulation of interleukin-1 beta secretion
• Cellular component: nuclear chromosome, telomeric region;cytoplasm;Golgi apparatus;cytosol;intracellular membrane-bounded organelle
• Molecular function: protein binding;ATP binding;Pyrin domain binding