NLRP8

Summary

NLRP8 (NLR family pyrin domain containing 8, HGNC:22940) is a protein-coding gene on chromosome 19q13.43, encoding NACHT, LRR and PYD domains-containing protein 8 (Q86W28). Involved in inflammation.

This gene encodes a member of the nucleotide-binding oligomerization domain/ leucine rich repeat/ pyrin domain containing (NLRP) subfamily, which belongs to the Nod-like receptor family of proteins. NLRP genes play roles in the mammalian innate immune system through inflammasome formation and activation of caspases. In addition, NLRP genes have been found to function during mammalian reproduction. Consistent with a function during human preimplantation development, this gene is expressed at high levels in oocytes with decreased levels in embryos. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 126205 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 198 total
• MANE Select transcript: NM_001433706

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22940
Approved symbol	NLRP8
Name	NLR family pyrin domain containing 8
Location	19q13.43
Locus type	gene with protein product
Status	Approved
Aliases	NOD16, PAN4, CLR19.2
Ensembl gene	ENSG00000179709
Ensembl biotype	protein_coding
OMIM	609659
Entrez	126205

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000291971, ENST00000590542, ENST00000850972

RefSeq mRNA: 2 — MANE Select: NM_001433706 NM_001317000, NM_001433706

CCDS: CCDS12937, CCDS82402

Canonical transcript exons

ENST00000850972 — 10 exons

Exon	Start	End
ENSE00001178447	55973652	55973822
ENSE00001178459	55976133	55976303
ENSE00001243768	55979394	55979564
ENSE00001243785	55970544	55970696
ENSE00001243793	55966213	55966380
ENSE00001243800	55954501	55956100
ENSE00001243805	55952538	55952612
ENSE00001243826	55947832	55948269
ENSE00001328716	55962067	55962237
ENSE00004283098	55981059	55981158

Expression profiles

Bgee: expression breadth tissue_specific, 3 present calls, max score 90.47.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	90.47	gold quality
oocyte	CL:0000023	75.61	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.99	gold quality
amniotic fluid	UBERON:0000173	60.24	gold quality
epithelium of nasopharynx	UBERON:0001951	58.66	gold quality
ventral tegmental area	UBERON:0002691	56.11	gold quality
mammary duct	UBERON:0001765	55.60	gold quality
buccal mucosa cell	CL:0002336	55.57	silver quality
jejunum	UBERON:0002115	55.43	gold quality
inferior vagus X ganglion	UBERON:0005363	54.20	gold quality
subthalamic nucleus	UBERON:0001906	53.96	gold quality
jejunal mucosa	UBERON:0000399	53.44	gold quality
gingival epithelium	UBERON:0001949	53.20	gold quality
dorsal plus ventral thalamus	UBERON:0001897	52.85	gold quality
layer of synovial tissue	UBERON:0007616	52.39	gold quality
dorsal root ganglion	UBERON:0000044	52.24	gold quality
saphenous vein	UBERON:0007318	52.24	gold quality
pericardium	UBERON:0002407	52.17	gold quality
substantia nigra pars reticulata	UBERON:0001966	52.14	gold quality
tongue	UBERON:0001723	52.13	gold quality
medulla oblongata	UBERON:0001896	52.13	gold quality
penis	UBERON:0000989	52.06	gold quality
nipple	UBERON:0002030	52.00	gold quality
synovial joint	UBERON:0002217	52.00	gold quality
thymus	UBERON:0002370	52.00	gold quality
pharyngeal mucosa	UBERON:0000355	51.87	gold quality
trachea	UBERON:0003126	51.85	gold quality
pylorus	UBERON:0001166	51.82	gold quality
renal medulla	UBERON:0000362	51.80	gold quality
body of tongue	UBERON:0011876	51.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting NLRP8, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-6831-5P	98.26	67.20	990
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334
HSA-MIR-4421	97.99	64.89	701
HSA-MIR-5699-3P	97.81	65.00	861
HSA-MIR-3927-3P	97.68	66.76	892
HSA-MIR-6791-3P	97.45	64.31	1123
HSA-MIR-6829-3P	97.45	64.31	1137
HSA-MIR-526B-5P	97.41	67.99	1074

Cross-species orthologs

0 orthologs

Paralogs (20): NLRP2 (ENSG00000022556), 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), NLRP11 (ENSG00000179873), NLRP10 (ENSG00000182261), NLRP9 (ENSG00000185792), PYDC2 (ENSG00000253548)

Protein

Protein identifiers

NACHT, LRR and PYD domains-containing protein 8 — Q86W28 (reviewed: Q86W28)

Alternative names: Nucleotide-binding oligomerization domain protein 16, PYRIN and NACHT-containing protein 4

All UniProt accessions (1): Q86W28

UniProt curated annotations — full annotation on UniProt →

Function. Involved in inflammation.

Subcellular location. Cytoplasm.

Similarity. Belongs to the NLRP family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q86W28-1	1	yes
Q86W28-2	2

RefSeq proteins (2): NP_001303929, NP_001420635* (*=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 (25 total): sequence variant 12, repeat 5, domain 2, region of interest 2, chain 1, compositionally biased region 1, binding site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86W28-F1	80.26	0.40

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): 210–217

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 28 (showing top): GOBP_INFLAMMATORY_RESPONSE, HATADA_METHYLATED_IN_LUNG_CANCER_DN, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_DEFENSE_RESPONSE, GOMF_ADENYL_NUCLEOTIDE_BINDING, LU_EZH2_TARGETS_DN, SRC_UP.V1_DN, ZNF146_TARGET_GENES, MIR8485, MIR4659A_3P_MIR4659B_3P, MIR5700, MIR7854_3P, JINESH_BLEBBISHIELD_TO_IMMUNE_CELL_FUSION_PBSHMS_UP

GO Biological Process (1): regulation of inflammatory response (GO:0050727)

GO Molecular Function (3): ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NLRP8	MEFV	O15553	744
NLRP8	CASP1	P29466	585
NLRP8	OR10P1	Q8NGE3	460
NLRP8	NLRC4	Q9NPP4	396
NLRP8	NAIP	Q13075	384
NLRP8	IFNGR2	P38484	371
NLRP8	IFNGR1	P15260	360
NLRP8	ZNF804B	A4D1E1	323
NLRP8	CARD19	Q96LW7	320
NLRP8	ZSCAN5B	A6NJL1	308
NLRP8	TRIM5	Q9C035	306
NLRP8	NLRP1	Q9C000	293
NLRP8	POTEC	B2RU33	290
NLRP8	ZSCAN5A	Q9BUG6	290
NLRP8	CARD8	Q9Y2G2	289

IntAct

2 interactions, top by confidence:

A	B	Type	Score
NLRP8	DNAJB5	psi-mi:“MI:0914”(association)	0.350

BioGRID (3): DNAJB5 (Affinity Capture-MS), DNAJB4 (Affinity Capture-MS), NLRP8 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JMD5, A1Z198, A3QJZ6, A3QJZ7, A6NGN4, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5G7, H0Y7S4, O60809, O60810, O60811, O60813, O95521, O95522, P0DUQ1, P0DUQ2, P78395, Q0GKD5, Q288C4, Q2LKU9, Q2LKV5, Q2LKW6, Q3TKR3, Q3UWY1, Q5SWL7, Q5SWL8, Q5TYX0, Q5VT98, Q5VTA0, Q5VWM3, Q5VWM4, Q5VWM6, Q5VXH4, Q5VXH5, Q66X05, Q66X19

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	162
Likely benign	12
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2095 predictions. Top by Δscore:

Variant	Effect	Δscore
19:55956099:GA:G	donor_gain	1.0000
19:55956101:G:GG	donor_gain	1.0000
19:55962062:T:G	acceptor_gain	1.0000
19:55976301:GGA:G	donor_gain	1.0000
19:55976302:GA:G	donor_gain	1.0000
19:55976302:GAG:G	donor_gain	1.0000
19:55976304:G:GG	donor_gain	1.0000
19:55979384:T:A	acceptor_gain	1.0000
19:55979565:G:GG	donor_gain	1.0000
19:55981135:A:G	donor_gain	1.0000
19:55981144:G:GT	donor_gain	1.0000
19:55948234:A:AG	donor_gain	0.9900
19:55948268:TGGT:T	donor_loss	0.9900
19:55948269:GGT:G	donor_loss	0.9900
19:55948270:G:GC	donor_loss	0.9900
19:55952537:GCC:G	acceptor_gain	0.9900
19:55954494:A:G	acceptor_gain	0.9900
19:55954496:TCTA:T	acceptor_loss	0.9900
19:55954497:CTAG:C	acceptor_loss	0.9900
19:55954498:TA:T	acceptor_loss	0.9900
19:55954499:AGGTA:A	acceptor_loss	0.9900
19:55956094:GCTC:G	donor_gain	0.9900
19:55962061:A:AG	acceptor_gain	0.9900
19:55962065:A:AG	acceptor_gain	0.9900
19:55962066:G:GG	acceptor_gain	0.9900
19:55962066:GAGC:G	acceptor_gain	0.9900
19:55962238:G:GG	donor_gain	0.9900
19:55966062:A:AG	acceptor_gain	0.9900
19:55970697:G:GG	donor_gain	0.9900
19:55976131:A:AG	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000114054 (19:55947819 T>A,C), RS1000165016 (19:55957579 G>A), RS1000221030 (19:55988628 G>A,C), RS1000225217 (19:55960534 A>G), RS1000244011 (19:55955135 G>A), RS1000297570 (19:55964113 G>A), RS1000359931 (19:55965091 G>T), RS1000385244 (19:55984525 A>G), RS1000453341 (19:55945845 G>A), RS1000646996 (19:55985079 G>A), RS1000790236 (19:55968036 A>G), RS1000816140 (19:55950688 G>A), RS1000831151 (19:55960217 G>A), RS1000837781 (19:55984728 T>C,G), RS1000921132 (19:55979011 C>T)

Disease associations

OMIM: gene MIM:609659 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001538_32	Immune reponse to smallpox (secreted IFN-alpha)	5.000000e-07
GCST001762_317	Obesity-related traits	8.000000e-06
GCST010206_11	Anorectal malformation	8.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0003940	physical activity

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs306468	NLRP8		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — NOD-like receptor family

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
bisphenol S	increases methylation	1
Hydrogen Peroxide	affects expression	1
Methapyrilene	increases methylation	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	decreases expression	1

Clinical trials (associated diseases)

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