NLRP2B

Summary

NLRP2B (NLR family pyrin domain containing 2B, HGNC:29887) is a protein-coding gene on chromosome Xp11.21, encoding NLR family pyrin domain-containing protein 2B (P0DMW2). May function as a negative regulator of NF-kappa-B by preventing RELA/p65 phosphorylation at ‘Ser-536’, thereby inhibiting its transcriptional activity.

Involved in several processes, including negative regulation of NF-kappaB transcription factor activity; negative regulation of peptidyl-serine phosphorylation; and negative regulation of signal transduction. Located in cytoplasm and nucleus.

Source: NCBI Gene 286430 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001319967

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29887
Approved symbol	NLRP2B
Name	NLR family pyrin domain containing 2B
Location	Xp11.21
Locus type	gene with protein product
Status	Approved
Aliases	NOD24, NALP2P, CLRX.1, POP4
Ensembl gene	ENSG00000215174
Ensembl biotype	protein_coding
Entrez	286430

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000434992

RefSeq mRNA: 1 — MANE Select: NM_001319967 NM_001319967

CCDS: CCDS83476

Canonical transcript exons

ENST00000434992 — 1 exons

Exon	Start	End
ENSE00001539840	57677067	57680260

Expression profiles

Bgee: expression breadth tissue_specific, 6 present calls, max score 93.27.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	93.27	gold quality
secondary oocyte	CL:0000655	88.39	gold quality
oocyte	CL:0000023	85.02	gold quality
Brodmann (1909) area 23	UBERON:0013554	59.32	gold quality
middle temporal gyrus	UBERON:0002771	58.96	gold quality
palpebral conjunctiva	UBERON:0001812	57.82	gold quality
esophagus squamous epithelium	UBERON:0006920	57.28	gold quality
epithelium of nasopharynx	UBERON:0001951	56.44	gold quality
gingiva	UBERON:0001828	48.74	gold quality
placenta	UBERON:0001987	47.61	gold quality
gingival epithelium	UBERON:0001949	46.78	gold quality
cortical plate	UBERON:0005343	46.77	gold quality
skeletal muscle tissue	UBERON:0001134	46.16	gold quality
muscle tissue	UBERON:0002385	45.14	gold quality
islet of Langerhans	UBERON:0000006	43.80	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
ventricular zone	UBERON:0003053	43.32	gold quality
trachea	UBERON:0003126	42.98	gold quality
superior frontal gyrus	UBERON:0002661	42.35	gold quality
entorhinal cortex	UBERON:0002728	42.34	gold quality
visceral pleura	UBERON:0002401	41.99	gold quality
parietal pleura	UBERON:0002400	41.86	gold quality
vastus lateralis	UBERON:0001379	41.74	gold quality
quadriceps femoris	UBERON:0001377	41.69	gold quality
hindlimb stylopod muscle	UBERON:0004252	41.67	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
medial globus pallidus	UBERON:0002477	41.17	gold quality
Brodmann (1909) area 9	UBERON:0013540	41.13	silver quality
colonic epithelium	UBERON:0000397	41.10	gold quality
tibia	UBERON:0000979	41.07	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

110 targeting NLRP2B, 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-4692	100.00	67.32	2066
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4514	99.99	67.10	1870
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-6793-5P	99.97	65.95	758
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6875-3P	99.82	70.26	2983

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

NLR family pyrin domain-containing protein 2B — P0DMW2 (reviewed: P0DMW2)

Alternative names: Pyrin domain-containing protein 2-like protein POP4, Pyrin-only protein 4

All UniProt accessions (1): P0DMW2

UniProt curated annotations — full annotation on UniProt →

Function. May function as a negative regulator of NF-kappa-B by preventing RELA/p65 phosphorylation at ‘Ser-536’, thereby inhibiting its transcriptional activity. Through NF-kappa-B regulation may control cytokine release upon Toll-like receptors activation and therefore play a role in modulation of innate immunity. May also play a role in cell cycle progression and apoptotic process.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in all tissues tested, including spleen, lymph node, thymus, tonsil, peripheral blood leukocyte, bone marrow, liver, heart, brain, placenta, lung, skeletal muscle, kidney and pancreas.

Induction. Up-regulated by inflammatory stimulus (LPS).

RefSeq proteins (1): NP_001306896* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004020	DAPIN	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily

Pfam: PF02758

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DMW2-F1	74.37	0.02

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 263 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_RIBOSOME_BIOGENESIS, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, MORF_MSH3, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOMF_NUCLEASE_ACTIVITY, SHEPARD_CRASH_AND_BURN_MUTANT_UP, MORF_BRCA1, GOBP_PEPTIDYL_SERINE_MODIFICATION, GOBP_TRNA_METABOLIC_PROCESS, MORF_ATRX

GO Biological Process (9): negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), obsolete negative regulation of NF-kappaB transcription factor activity (GO:0032088), negative regulation of peptidyl-serine phosphorylation (GO:0033137), negative regulation of toll-like receptor signaling pathway (GO:0034122), positive regulation of apoptotic process (GO:0043065), innate immune response (GO:0045087), negative regulation of cell cycle (GO:0045786), immune system process (GO:0002376), negative regulation of signal transduction (GO:0009968)

GO Molecular Function (0):

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
negative regulation of protein phosphorylation	1
peptidyl-serine phosphorylation	1
regulation of peptidyl-serine phosphorylation	1
toll-like receptor signaling pathway	1
negative regulation of immune system process	1
negative regulation of signal transduction	1
regulation of toll-like receptor signaling pathway	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
immune response	1
defense response to symbiont	1
cell cycle	1
negative regulation of cellular process	1
regulation of cell cycle	1
biological_process	1
signal transduction	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

281 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NLRP2B	CARD17P	Q5XLA6	480
NLRP2B	NLRP7	Q8WX94	480
NLRP2B	CARD18	P57730	455
NLRP2B	NLRC3	Q7RTR2	433
NLRP2B	PYDC1	Q8WXC3	430
NLRP2B	CARD16	Q5EG05	377
NLRP2B	MEFV	O15553	361
NLRP2B	NOD1	Q9Y239	357
NLRP2B	PIGX	Q8TBF5	309
NLRP2B	AIM2	O14862	272
NLRP2B	NLRC5	Q86WI3	252
NLRP2B	ADAT2	Q7Z6V5	247
NLRP2B	NLRP4	Q96MN2	247
NLRP2B	CASP1	P29466	247
NLRP2B	NLRP10	Q86W26	246
NLRP2B	NLRP12	P59046	246

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: O33508, O33509, O33510, O33535, O33543, O33544, O33545, O33575, O54457, P01205, P02875, P0DMW2, P11419, P16992, P20120, P20655, P23032, P24477, P28848, P31954, P34667, P36230, P37154, P38223, P38473, P39495, P63289, P63290, P63291, P68354, P80568, P80613, P81063, P81163, P81175, P82303, P83367, P84196, P84488, P84538

Diamond homologs: P0DMW2, Q56P42, Q8WX94, Q9NX02, Q96MN2, A6QLE5, B0FPE9, D4A523, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5R7, P10775, P13489, P29315, P59044, P59045, P59046, P59047, Q288C4, Q2LKU9, Q3TKR3, Q647I9, Q66X03, Q66X05, Q6B966, Q7RTR0, Q86W24, Q86W25, Q86W26, Q86W28, Q8BU40, Q8C6J9, Q8CCN1, Q8HZP9, Q8R4B8, Q91VI7, Q91WS2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1055 predictions. Top by Δscore:

Variant	Effect	Δscore
19:29606324:GA:G	donor_gain	1.0000
19:29606326:G:GG	donor_gain	1.0000
19:29610591:G:GT	donor_gain	1.0000
19:29610594:G:GT	donor_gain	1.0000
19:29610630:GAG:G	donor_gain	1.0000
19:29610632:GG:G	donor_loss	1.0000
19:29610633:GT:G	donor_loss	1.0000
19:29610634:T:G	donor_loss	1.0000
19:29611848:T:A	acceptor_gain	1.0000
19:29611857:T:A	acceptor_gain	1.0000
19:29611857:TGCA:T	acceptor_loss	1.0000
19:29611858:GCA:G	acceptor_loss	1.0000
19:29611860:A:AG	acceptor_gain	1.0000
19:29611861:G:GA	acceptor_gain	1.0000
19:29611935:GACAC:G	donor_gain	1.0000
19:29611940:G:GG	donor_gain	1.0000
19:29615242:A:AG	acceptor_gain	1.0000
19:29615243:G:GG	acceptor_gain	1.0000
19:29615243:GTT:G	acceptor_gain	1.0000
19:29606321:GAAGA:G	donor_gain	0.9900
19:29608651:CCCCA:C	acceptor_loss	0.9900
19:29608652:CCCAG:C	acceptor_loss	0.9900
19:29608653:CCA:C	acceptor_loss	0.9900
19:29608654:CAGG:C	acceptor_loss	0.9900
19:29608655:AGGTG:A	acceptor_loss	0.9900
19:29610407:A:AG	acceptor_gain	0.9900
19:29610408:G:GG	acceptor_gain	0.9900
19:29610408:GC:G	acceptor_gain	0.9900
19:29610586:C:T	donor_gain	0.9900
19:29611842:T:TA	acceptor_gain	0.9900

AlphaMissense

286 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:57680184:A:G	F26S	0.893
X:57680234:G:C	F9L	0.889
X:57680234:G:T	F9L	0.889
X:57680236:A:G	F9L	0.889
X:57680183:G:C	F26L	0.862
X:57680183:G:T	F26L	0.862
X:57680185:A:G	F26L	0.862
X:57680184:A:C	F26C	0.774
X:57680180:C:A	K27N	0.769
X:57680180:C:G	K27N	0.769
X:57680175:A:G	L29P	0.753
X:57680193:A:G	L23S	0.685
X:57680208:A:G	L18P	0.678
X:57680235:A:G	F9S	0.645
X:57680179:A:G	S28P	0.632
X:57680172:A:C	I30S	0.615
X:57680208:A:T	L18H	0.611
X:57680220:A:G	L14P	0.597
X:57680229:A:G	L11P	0.584
X:57680172:A:T	I30N	0.579
X:57680229:A:T	L11Q	0.577

dbSNP variants (sampled 300 via entrez): RS1000305314 (X:57678194 C>A,G,T), RS1001002450 (X:57679409 C>A,G,T), RS1001187470 (X:57679300 A>G,T), RS1001476961 (X:57677906 G>T), RS1001844377 (X:57677621 G>T), RS1003230127 (X:57681351 T>A,G), RS1003262685 (X:57681677 T>C), RS1003530526 (X:57680478 C>T), RS1003559653 (X:57676591 C>T), RS1003583538 (X:57680231 G>A,T), RS1004440696 (X:57680857 C>T), RS1004449387 (X:57681016 G>T), RS1005546895 (X:57678360 T>C), RS1006157448 (X:57680093 T>A), RS1007264495 (X:57679265 C>A,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	decreases expression, affects cotreatment	1
Cadmium	increases expression	1
Copper	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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