NLRP2

Summary

NLRP2 (NLR family pyrin domain containing 2, HGNC:22948) is a protein-coding gene on chromosome 19q13.42, encoding NACHT, LRR and PYD domains-containing protein 2 (Q9NX02). Suppresses TNF- and CD40-induced NFKB1 activity at the level of the IKK complex, by inhibiting NFKBIA degradation induced by TNF.

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). Members of this gene family are thought to be important regulators of immune responses. This gene product interacts with components of the IkB kinase (IKK) complex, and can regulate both caspase-1 and NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity. The pyrin domain is necessary and sufficient for suppression of NF-kB activity. An allelic variant (rs147585490) has been found that is incapable of blocking the transcriptional activity of NF-kB. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 55655 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oocyte/zygote/embryo maturation arrest 18 (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 410 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 3
• MANE Select transcript: NM_017852

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22948
Approved symbol	NLRP2
Name	NLR family pyrin domain containing 2
Location	19q13.42
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20510, PYPAF2, NBS1, PAN1, CLR19.9
Ensembl gene	ENSG00000022556
Ensembl biotype	protein_coding
OMIM	609364
Entrez	55655

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 15 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000263437, ENST00000339757, ENST00000381637, ENST00000391721, ENST00000397169, ENST00000427260, ENST00000433772, ENST00000448584, ENST00000537859, ENST00000539848, ENST00000540005, ENST00000540597, ENST00000542755, ENST00000543010, ENST00000543277, ENST00000585500, ENST00000586512, ENST00000588107, ENST00000588619, ENST00000875545, ENST00000944275

RefSeq mRNA: 5 — MANE Select: NM_017852 NM_001174081, NM_001174082, NM_001174083, NM_001348003, NM_017852

CCDS: CCDS12913, CCDS54318, CCDS54319, CCDS86807

Canonical transcript exons

ENST00000448584 — 13 exons

Exon	Start	End
ENSE00002276716	54966374	54966467
ENSE00003461265	54994269	54994439
ENSE00003480556	54974500	54974544
ENSE00003480852	54985047	54985217
ENSE00003505640	54969999	54970295
ENSE00003532224	54982162	54983728
ENSE00003556646	54990502	54990672
ENSE00003597391	54977752	54977823
ENSE00003614045	54986151	54986315
ENSE00003631741	55000760	55001138
ENSE00003644233	54997317	54997487
ENSE00003785368	54981617	54981682
ENSE00003895922	54990022	54990192

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 89.36.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8988 / max 40.1412, expressed in 358 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177570	0.7866	327
177569	0.1050	35
208935	0.0073	1

Top tissues by expression

136 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.36	gold quality
placenta	UBERON:0001987	89.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.95	gold quality
granulocyte	CL:0000094	85.66	gold quality
testis	UBERON:0000473	84.51	gold quality
left testis	UBERON:0004533	84.45	gold quality
right testis	UBERON:0004534	84.35	gold quality
cortical plate	UBERON:0005343	82.81	gold quality
ganglionic eminence	UBERON:0004023	81.55	gold quality
mucosa of transverse colon	UBERON:0004991	79.03	gold quality
lymph node	UBERON:0000029	78.79	gold quality
blood	UBERON:0000178	77.71	gold quality
ventricular zone	UBERON:0003053	77.63	gold quality
endometrium	UBERON:0001295	77.34	gold quality
islet of Langerhans	UBERON:0000006	77.05	gold quality
esophagus mucosa	UBERON:0002469	77.04	gold quality
tonsil	UBERON:0002372	75.43	gold quality
vermiform appendix	UBERON:0001154	75.30	gold quality
spleen	UBERON:0002106	75.07	gold quality
primary visual cortex	UBERON:0002436	74.94	gold quality
duodenum	UBERON:0002114	74.23	gold quality
bone marrow cell	CL:0002092	74.06	gold quality
bone marrow	UBERON:0002371	73.62	gold quality
skin of abdomen	UBERON:0001416	73.42	gold quality
thyroid gland	UBERON:0002046	72.92	gold quality
right lobe of thyroid gland	UBERON:0001119	72.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.69	gold quality
left lobe of thyroid gland	UBERON:0001120	72.11	gold quality
superior frontal gyrus	UBERON:0002661	71.96	gold quality
pancreas	UBERON:0001264	71.40	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.08
E-MTAB-6911	no	47.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, LMX1B, NFKB1, NFKB, PDX1, RELA

miRNA regulators (miRDB)

13 targeting NLRP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-379-3P	99.69	69.60	1524
HSA-MIR-411-3P	99.69	69.63	1524
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-6765-3P	97.83	64.59	1165

Literature-anchored findings (GeneRIF, showing 32)

• functions as a modulator of the activation of NF-kappaB and pro-caspase-1 in macrophages (PMID:15456791)
• PYPAF3 is a feedback regulator of interleukin-1beta secretion, and PYPAF2 and PYPAF3, together with PYNOD, constitute an anti-inflammatory subgroup of PYRIN-containing apoptotic protease-activating factor-1-like proteins (PMID:15817483)
• These findings provide molecular insight into the expression of NLRP2 by NF-kappaB. (PMID:18056399)
• NLRP2 was preferentially expressed from the maternal allele (PMID:18369178)
• Common variants in NLRP2 and NLRP3 genes are strong prognostic factors for the outcome of HLA-identical sibling allogeneic stem cell transplantation. (PMID:18772453)
• These data show that TLR2 and NALP2 mediate the induction of human beta-defensins by F. nucleatum in gingival epithelial cells (PMID:19103770)
• NLRP2 has a previously unrecognised role in establishing or maintaining genomic imprinting in humans. (PMID:19300480)
• Roles of the pyrin protein which seems to have various roles in regulation of innate immunity, inflammation, and apoptosis. (PMID:19534089)
• Our observations are the first to implicate SPARC, SLPI, and NLRP2, a component of the innate immune system, in the pathogenesis of axial spondyloarthropathy (PMID:19900269)
• POP2 acts as a regulator of inflammatory signals and exerts its two known functions through distinct modalities employed by its first alpha-helix (PMID:21976665)
• Observations suggest that although NLRP7 and C6orf221 mutations are related to diploid biparental FRHMs, neither of these genes, nor NLRP2, are related to diploid HMs with biparental contributions to the molar genome. (PMID:22909446)
• There is a significant association of a tag single-nucleotide polymorphism (SNP) of NLRP7 (rs26949) with idiopathic recurrent miscarriage (PMID:23360675)
• The results of this study suggest that the astrocytic NLRP2 inflammasome is an important component of the CNS inflammatory response (PMID:23625868)
• single nucleotide polymorphisms in NALP2 gene is associated with arsenic induced skin lesions, peripheral neuropathy, eye problem and respiratory diseases. (PMID:23644288)
• This study indicates that polymorphisms in SPARC and NLRP2 are related to rheumatoid arthritis susceptibility in a Chinese Han population. (PMID:24754275)
• 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). (PMID:24871464)
• No disease-causing mutations were identified in NLRP2, NLRP7 and KHDC3L in cohorts of unexplained infertility and recurrent pregnancy loss. (PMID:25376457)
• genetic polymorphism is associated with chronic pancreatitis (PMID:26253076)
• During transition from the pluripotent stage towards the neural developmental stage, NLRP2 is differentially expressed in bipolar patient derived cells compared to control derived cells. (PMID:28117838)
• Early-onset childhood atopic dermatitis is related to NLRP2 repression. (PMID:29233739)
• We now report 15 further pedigrees in which offspring had disturbance of imprinting, while their mothers had rare, predicted-deleterious variants in maternal effect genes, including NLRP2, NLRP7 and PADI6 (PMID:29574422)
• The NLRP2-TBK1 axis may serve as an additional signaling cascade to maintain immune homeostasis in response to viral infection. (PMID:30183071)
• NLRP2 missense mutation was identified in patients with multilocus imprinting disturbances. NLRP2 pathogenic mutation affects protein conformation and activity. (PMID:30221575)
• NLRP2 served an important role in maintaining cell viability. (PMID:30431084)
• NLRP2 might be a potential target for developing effective therapeutic strategy to prevent Nonalcoholic fatty liver disease progression. (PMID:30454891)
• NLRP2 and NLRP5 are novel mutant genes responsible for human early embryonic arrest. (PMID:30877238)
• Somatic Mutation of NLRP Genes in Gastric and Colonic Cancers. (PMID:34257569)
• Gene body hypomethylation of pyroptosis-related genes NLRP7, NLRP2, and NLRP3 facilitate non-invasive surveillance of hepatocellular carcinoma. (PMID:37273114)
• NLRP2 in health and disease. (PMID:37735978)
• Nlrp2 deletion ameliorates kidney damage in a mouse model of cystinosis. (PMID:38633264)
• HLA-C expression in extravillous trophoblasts is determined by an ELF3-NLRP2/NLRP7 regulatory axis. (PMID:39052836)
• Variants in NLRP2 and ZFP36L2, non-core components of the human subcortical maternal complex, cause female infertility with embryonic development arrest. (PMID:39178021)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nlrp2	ENSMUSG00000035177
rattus_norvegicus	Nlrp2	ENSRNOG00000049759

Paralogs (20): NLRP1 (ENSG00000091592), NOD1 (ENSG00000106100), NLRC5 (ENSG00000140853), NLRP12 (ENSG00000142405), NLRP14 (ENSG00000158077), NLRP4 (ENSG00000160505), NLRX1 (ENSG00000160703), NLRP3 (ENSG00000162711), NOD2 (ENSG00000167207), NLRP7 (ENSG00000167634), NLRC3 (ENSG00000167984), NLRP5 (ENSG00000171487), NLRP13 (ENSG00000173572), NLRP6 (ENSG00000174885), CIITA (ENSG00000179583), NLRP8 (ENSG00000179709), NLRP11 (ENSG00000179873), NLRP10 (ENSG00000182261), NLRP9 (ENSG00000185792), PYDC2 (ENSG00000253548)

Protein

Protein identifiers

NACHT, LRR and PYD domains-containing protein 2 — Q9NX02 (reviewed: Q9NX02)

Alternative names: Nucleotide-binding site protein 1, PYRIN domain and NACHT domain-containing protein 1, PYRIN-containing APAF1-like protein 2

All UniProt accessions (11): A0A0G2JLJ4, Q9NX02, F5GYZ4, F5H5B1, F5H7Q5, H0YH35, J3KN39, K7EJ90, K7ELX1, K7EMK2, K7EPE6

UniProt curated annotations — full annotation on UniProt →

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 pro-inflammatory 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 pro-inflammatory caspases.

Subunit / interactions. Interacts with CHUK. Interacts with IKBKB. Interacts with IKBKG. Interacts with MEFV. Interacts with PYCARD. Interacts (via pyrin domain) with PYDC2. Interacts with CARD8.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed at high levels in lung, placenta and thymus and at lower levels in ovary, intestine and brain. Highly abundant in oocytes and early embryos, however poorly expressed in somatic tissues such as brain, kidney, liver and spinal cord.

Disease relevance. Oocyte/zygote/embryo maturation arrest 18 (OZEMA18) [MIM:620332] An autosomal recessive female infertility disorder. In affected women, ovulation and fertilization proceed normally but embryos are arrested at early stages of development or cannot establish pregnancy after implantation. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. When isolated, the NACHT domain is involved in interaction with CARD8. This interaction is not detected for the full-length protein, maybe due to autoinhibition, this inhibition might by relieved by an inducible change in protein folding. The pyrin domain is necessary and sufficient for suppression of NFKB1 activation induced by TNF and for inducing IL1B secretion in collaboration with caspase-1. It is involved in interaction with PYCARD.

Induction. By interferons and bacterial lipopolysaccharides (LPS).

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the NLRP family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9NX02-1	1	yes
Q9NX02-2	2
Q9NX02-3	3
Q9NX02-4	4
Q9NX02-5	5

RefSeq proteins (5): NP_001167552, NP_001167553, NP_001167554, NP_001334932, NP_060322* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001611	Leu-rich_rpt	Repeat
IPR004020	DAPIN	Domain
IPR007111	NACHT_NTPase	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR041075	NOD1/2_WH	Domain
IPR041267	NLRP_HD2	Domain
IPR050637	NLRP_innate_immun_reg	Family

Pfam: PF02758, PF05729, PF13516, PF17776, PF17779

UniProt features (39 total): sequence variant 15, repeat 8, sequence conflict 7, splice variant 4, domain 2, chain 1, binding site 1, modified residue 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9C6V	X-RAY DIFFRACTION	1.7
9C6W	X-RAY DIFFRACTION	1.7
9C6X	X-RAY DIFFRACTION	1.7
9L4L	ELECTRON MICROSCOPY	3.4
9L4K	ELECTRON MICROSCOPY	3.41

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NX02-F1	81.44	0.41

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 213–220

Post-translational modifications (1): 671

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 98 (showing top): GOBP_INFLAMMATORY_RESPONSE, GOBP_SPINDLE_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_INTERLEUKIN_1_PRODUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, PATIL_LIVER_CANCER, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_REGULATION_OF_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_NON_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, TIEN_INTESTINE_PROBIOTICS_24HR_UP

GO Biological Process (8): apoptotic process (GO:0006915), inflammatory response (GO:0006954), positive regulation of interleukin-1 beta production (GO:0032731), innate immune response (GO:0045087), regulation of inflammatory response (GO:0050727), negative regulation of non-canonical NF-kappaB signal transduction (GO:1901223), immune system process (GO:0002376), regulation of interleukin-1 beta production (GO:0032651)

GO Molecular Function (4): ATP binding (GO:0005524), Pyrin domain binding (GO:0032090), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), chromosome, telomeric region (GO:0000781)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
interleukin-1 beta production	2
cellular anatomical structure	2
cytoplasm	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
defense response	1
regulation of interleukin-1 beta production	1
positive regulation of interleukin-1 production	1
immune response	1
defense response to symbiont	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
non-canonical NF-kappaB signal transduction	1
regulation of non-canonical NF-kappaB signal transduction	1
negative regulation of intracellular signal transduction	1
biological_process	1
regulation of interleukin-1 production	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein domain specific binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
chromosomal region	1

Protein interactions and networks

STRING

939 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NLRP2	NLRP1	Q9C000	984
NLRP2	CASP1	P29466	975
NLRP2	NLRC4	Q9NPP4	974
NLRP2	AIM2	O14862	963
NLRP2	NLRP12	P59046	925
NLRP2	MEFV	O15553	922
NLRP2	NLRP6	P59044	903
NLRP2	CARD8	Q9Y2G2	880
NLRP2	CASP5	P51878	863
NLRP2	PYCARD	Q9ULZ3	847
NLRP2	SLA	Q13239	846
NLRP2	TLE6	Q9H808	813
NLRP2	NLRP3	Q96P20	811
NLRP2	KHDC3L	Q587J8	805
NLRP2	OOEP	A6NGQ2	779

IntAct

51 interactions, top by confidence:

A	B	Type	Score
RFXANK	RFXAP	psi-mi:“MI:0914”(association)	0.780
PYDC2	NLRP2	psi-mi:“MI:0915”(physical association)	0.600
NLRP2	PYDC2	psi-mi:“MI:0915”(physical association)	0.600
NLRP2	PYDC2	psi-mi:“MI:0403”(colocalization)	0.600
PFDN1	ARHGAP32	psi-mi:“MI:0914”(association)	0.530
NLRP2	ATG16L1	psi-mi:“MI:0915”(physical association)	0.500
NLRP2	NLRP7	psi-mi:“MI:0915”(physical association)	0.460
NLRP2	NLRP7	psi-mi:“MI:0403”(colocalization)	0.460
NLRP2	H2AX	psi-mi:“MI:0915”(physical association)	0.460
H2AX	NLRP2	psi-mi:“MI:0403”(colocalization)	0.460
NLRP2	SUGT1	psi-mi:“MI:0915”(physical association)	0.400
NLRP2	WRN	psi-mi:“MI:0915”(physical association)	0.400
NLRP2	RBBP6	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
PA	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG7	IFT56	psi-mi:“MI:0914”(association)	0.350
SSUH2	IGLC7	psi-mi:“MI:0914”(association)	0.350
NPAS1	CIBAR1	psi-mi:“MI:0914”(association)	0.350
NCR3	POTEF	psi-mi:“MI:0914”(association)	0.350
PLEKHG7	MROH6	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
UBXN6	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PSG11	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
CRYBB3	ARHGAP32	psi-mi:“MI:0914”(association)	0.350

BioGRID (48): GAPDH (Co-fractionation), LARP1 (Co-fractionation), TPP1 (Affinity Capture-MS), RBBP6 (Affinity Capture-MS), TAF13 (Affinity Capture-MS), TTF1 (Affinity Capture-MS), BECN1 (Affinity Capture-MS), BCL7B (Affinity Capture-MS), CRIPT (Affinity Capture-MS), NLRP5 (Affinity Capture-MS), NLRP2 (Proximity Label-MS), RAD50 (Affinity Capture-Western), MRE11A (Affinity Capture-Western), NLRP2 (Affinity Capture-MS), NLRP2 (Affinity Capture-MS)

ESM2 similar proteins: A1Z198, A6QLE5, B0FPE9, D4A523, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5G7, E9Q5R7, P59045, P59046, P59047, Q0GKD5, Q288C4, Q2LKU9, Q2LKV2, Q2LKV5, Q2LKW6, Q3TKR3, Q3UWY1, Q63035, Q647I9, Q66X01, Q66X03, Q66X05, Q66X19, Q66X22, Q6B966, Q7RTR0, Q7TPX8, Q86W24, Q86W25, Q86W26, Q86W28, Q8BU40, Q8BVP1, Q8C6J9, Q8CCN1

Diamond homologs: A0A386CAB9, A1Z198, A6QLE5, B0FPE9, D4A523, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5R7, O15553, P10775, P13489, P29315, P59044, P59045, P59046, Q0GKD5, Q288C4, Q2LKU9, Q2LKV2, Q2LKV5, Q2LKW6, Q3TKR3, Q63035, Q647I9, Q66X01, Q66X03, Q66X19, Q6B966, Q7RTR0, Q86W24, Q86W25, Q86W26, Q86W28, Q8BU40, Q8C6J9, Q8CCN1, Q8HZP9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

410 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	231
Likely benign	97
Benign	31

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
2499456	NM_017852.5(NLRP2):c.1961C>A (p.Ser654Ter)	Pathogenic
2499457	NM_017852.5(NLRP2):c.773T>C (p.Phe258Ser)	Pathogenic
2499458	NM_017852.5(NLRP2):c.2254C>T (p.Arg752Ter)	Pathogenic
4528336	NM_017852.5(NLRP2):c.2537+1G>C	Likely pathogenic

SpliceAI

1816 predictions. Top by Δscore:

Variant	Effect	Δscore
19:54969984:T:A	acceptor_gain	1.0000
19:54970293:GAG:G	donor_gain	1.0000
19:54970295:GGTG:G	donor_loss	1.0000
19:54970296:GT:G	donor_loss	1.0000
19:54970297:T:A	donor_loss	1.0000
19:54974498:A:AG	acceptor_gain	1.0000
19:54974499:G:GA	acceptor_gain	1.0000
19:54977746:CTCCA:C	acceptor_loss	1.0000
19:54977747:TCCAG:T	acceptor_loss	1.0000
19:54977748:CCA:C	acceptor_loss	1.0000
19:54977749:CAG:C	acceptor_loss	1.0000
19:54977750:A:AG	acceptor_gain	1.0000
19:54977750:AG:A	acceptor_gain	1.0000
19:54977750:AGG:A	acceptor_gain	1.0000
19:54977751:G:GG	acceptor_gain	1.0000
19:54977751:GG:G	acceptor_gain	1.0000
19:54977751:GGG:G	acceptor_gain	1.0000
19:54977821:AAGGT:A	donor_loss	1.0000
19:54977822:AGGT:A	donor_loss	1.0000
19:54977823:GGTG:G	donor_loss	1.0000
19:54977824:G:C	donor_loss	1.0000
19:54977825:T:G	donor_loss	1.0000
19:54983729:GT:G	donor_loss	1.0000
19:54983730:T:A	donor_loss	1.0000
19:54985045:A:AG	acceptor_gain	1.0000
19:54985045:A:C	acceptor_loss	1.0000
19:54985046:G:GG	acceptor_gain	1.0000
19:54985213:GTGGT:G	donor_gain	1.0000
19:54985214:TGGT:T	donor_gain	1.0000
19:54985215:GGTG:G	donor_gain	1.0000

AlphaMissense

6996 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:54982354:A:T	K219I	0.986
19:54970092:T:C	F26S	0.971
19:54970091:T:C	F26L	0.970
19:54970093:C:A	F26L	0.970
19:54970093:C:G	F26L	0.970
19:54970257:G:C	R81P	0.967
19:54982355:A:C	K219N	0.967
19:54982355:A:T	K219N	0.967
19:54982425:T:C	F243L	0.965
19:54982427:C:A	F243L	0.965
19:54982427:C:G	F243L	0.965
19:54982699:T:A	V334D	0.965
19:54982413:T:C	F239L	0.962
19:54982415:C:A	F239L	0.962
19:54982415:C:G	F239L	0.962
19:54970068:T:C	L18P	0.961
19:54982354:A:C	K219T	0.961
19:54982656:A:C	S320R	0.961
19:54982658:T:A	S320R	0.961
19:54982658:T:G	S320R	0.961
19:54990582:T:C	L873P	0.960
19:54997413:T:A	N992K	0.959
19:54997413:T:G	N992K	0.959
19:54970096:G:C	K27N	0.958
19:54970096:G:T	K27N	0.958
19:54982386:T:A	W230R	0.958
19:54982386:T:C	W230R	0.958
19:54982549:T:C	L284S	0.958
19:54985141:A:C	S709R	0.957
19:54985143:C:A	S709R	0.957

dbSNP variants (sampled 300 via entrez): RS1000013379 (19:54986055 G>A,C), RS1000024865 (19:54973348 T>G), RS1000027472 (19:54999278 G>C,T), RS1000145931 (19:54996956 G>A), RS1000161328 (19:54970682 G>C,T), RS1000214121 (19:54984472 G>A,T), RS1000305297 (19:54989947 C>A,T), RS1000461590 (19:54973615 C>T), RS1000471697 (19:54986210 A>G), RS1000602173 (19:54989095 C>T), RS1000616685 (19:54970925 C>G,T), RS1000665140 (19:54966688 G>A), RS1000682363 (19:54980082 C>G,T), RS1000708707 (19:54980268 G>A), RS1000743534 (19:54980861 G>T)

Disease associations

OMIM: gene MIM:609364 | disease phenotypes: MIM:620332

GenCC curated gene-disease

Disease	Classification	Inheritance
oocyte/zygote/embryo maturation arrest 18	Strong	Autosomal recessive

Mondo (1): oocyte/zygote/embryo maturation arrest 18 (MONDO:0957230)

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0008222	Female infertility
HP:0011462	Young adult onset

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001725_62	Inflammatory bowel disease	7.000000e-11
GCST009030_30	Venous thromboembolism	3.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — NOD-like receptor family

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	2
Vehicle Emissions	decreases reaction, increases expression, decreases expression, increases abundance	2
Valproic Acid	increases expression, increases methylation	2
Particulate Matter	decreases reaction, increases expression, decreases expression, increases abundance	2
triphenyl phosphate	affects expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment, decreases expression	1
sodium arsenate	decreases expression	1
arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4(2’-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression	1
Cisplatin	decreases response to substance, increases expression	1
Copper	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Ivermectin	increases expression	1
Methapyrilene	increases methylation	1
Ozone	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.