NLRP10

Summary

NLRP10 (NLR family pyrin domain containing 10, HGNC:21464) is a protein-coding gene on chromosome 11p15.4, encoding NACHT, LRR and PYD domains-containing protein 10 (Q86W26). Inhibits autoprocessing of CASP1, CASP1-dependent IL1B secretion, PYCARD aggregation and PYCARD-mediated apoptosis but not apoptosis induced by FAS or BID.

Members of the NALP protein family typically contain a NACHT domain, a NACHT-associated domain (NAD), a C-terminal leucine-rich repeat (LRR) region, and an N-terminal pyrin domain (PYD). The protein encoded by this gene belongs to the NALP protein family despite lacking the LRR region. This protein likely plays a regulatory role in the innate immune system. The protein belongs to the signal-induced multiprotein complex, the inflammasome, that activates the pro-inflammatory caspases, caspase-1 and caspase-5. Other experiments indicate that this gene acts as a multifunctional negative regulator of inflammation and apoptosis.

Source: NCBI Gene 338322 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 115 total
• MANE Select transcript: NM_001391958

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21464
Approved symbol	NLRP10
Name	NLR family pyrin domain containing 10
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	NOD8, PAN5, Pynod, CLR11.1
Ensembl gene	ENSG00000182261
Ensembl biotype	protein_coding
OMIM	609662
Entrez	338322

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000328600, ENST00000691676

RefSeq mRNA: 2 — MANE Select: NM_001391958 NM_001391958, NM_176821

CCDS: CCDS7784

Canonical transcript exons

ENST00000612291 — 0 exons

Expression profiles

Bgee: expression breadth broad, 32 present calls, max score 74.10.

FANTOM5 (CAGE): breadth broad, TPM avg 0.7205 / max 39.7089, expressed in 244 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118485	0.5589	200
118486	0.0991	57
118484	0.0625	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of leg	UBERON:0001511	74.10	gold quality
zone of skin	UBERON:0000014	72.61	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	70.71	silver quality
skin of abdomen	UBERON:0001416	70.05	gold quality
stromal cell of endometrium	CL:0002255	57.70	gold quality
placenta	UBERON:0001987	53.71	gold quality
calcaneal tendon	UBERON:0003701	47.57	silver quality
endometrium	UBERON:0001295	45.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	45.39	gold quality
monocyte	CL:0000576	45.32	gold quality
leukocyte	CL:0000738	44.95	gold quality
lower esophagus mucosa	UBERON:0035834	43.89	silver quality
vermiform appendix	UBERON:0001154	43.79	silver quality
muscle of leg	UBERON:0001383	43.06	silver quality
gastrocnemius	UBERON:0001388	42.42	silver quality
sural nerve	UBERON:0015488	42.26	gold quality
thoracic mammary gland	UBERON:0005200	42.14	gold quality
bone marrow	UBERON:0002371	42.13	gold quality
smooth muscle tissue	UBERON:0001135	41.26	silver quality
cortical plate	UBERON:0005343	39.77	gold quality
primary visual cortex	UBERON:0002436	39.74	gold quality
granulocyte	CL:0000094	39.29	gold quality
adrenal tissue	UBERON:0018303	39.06	gold quality
multicellular organism	UBERON:0000468	38.98	gold quality
cortex of kidney	UBERON:0001225	38.87	gold quality
gall bladder	UBERON:0002110	38.57	gold quality
lymph node	UBERON:0000029	38.38	gold quality
bone marrow cell	CL:0002092	38.24	gold quality
corpus callosum	UBERON:0002336	37.98	gold quality
ascending aorta	UBERON:0001496	37.91	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.16

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, TP53

Literature-anchored findings (GeneRIF, showing 13)

• PYNOD is a novel regulator of apoptosis and inflammation. (PMID:15096476)
• 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)
• The structural modification of the NLRP10 gene might have played a role in development or enhancement of human-specific traits during evolution. (PMID:19544093)
• Transgenic PYNOD colocalizes with apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and inhibits caspase-1-mediated interleukin (IL)-1beta processing without inhibiting caspase-4-mediated caspase-1 processing. (PMID:20393137)
• The results show that either deletion of the p53 binding elements within the PYNOD promoter or treatment with p53 inhibitor could significantly reduce PYNOD promoter activity. (PMID:22365966)
• These data revealed a novel role of NLRP10 in innate immune responses towards bacterial infection and suggest that NLRP10 functions as a scaffold for the formation of the NOD1-Nodosome. (PMID:22672233)
• Review summarize recent advances of the role of of human and murine NLRP10 in innate and adaptive immune responses. [Review] (PMID:23562614)
• these data suggest that NLRP10 is involved in activating the ERK signalling pathway in oral epithelial cell line infected with Tannerella forsythia and Fusobacterium nucleatum (PMID:28766990)
• Authors observed an important role of NLRP10 in cytokine and chemokine production as well as expression of NF-kappaB and MAPKs in CSE-exposed A549 cells. Furthermore, replenishment of A549 cell culture with recombinant IL-17A (rIL-17A) during NLRP10 knockdown rescued CSE-induced inflammatory responses. (PMID:29501574)
• this study shows that NLRP10 affects the stability of Abin-1 to control inflammatory responses (PMID:30510071)
• Association of HLA-DPB1, NLRP10, OVOL1, and ABCC11 with the axillary microbiome in a Japanese population. (PMID:35078690)
• NLRP10 promotes AGEs-induced NLRP1 and NLRP3 inflammasome activation via ROS/MAPK/NF-kappaB signaling in human periodontal ligament cells. (PMID:37043073)
• NLRP10 maintains epidermal homeostasis by promoting keratinocyte survival and P63-dependent differentiation and barrier function. (PMID:39424623)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	nlrp1	ENSDARG00000088423
danio_rerio	nlrb5	ENSDARG00000090699
danio_rerio	si:ch211-66k16.2	ENSDARG00000095634
danio_rerio		ENSDARG00000105141
mus_musculus	Nlrp10	ENSMUSG00000049709
rattus_norvegicus	Nlrp10	ENSRNOG00000015082

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), NLRP8 (ENSG00000179709), NLRP11 (ENSG00000179873), NLRP9 (ENSG00000185792), PYDC2 (ENSG00000253548)

Protein

Protein identifiers

NACHT, LRR and PYD domains-containing protein 10 — Q86W26 (reviewed: Q86W26)

Alternative names: Nucleotide-binding oligomerization domain protein 8

All UniProt accessions (1): Q86W26

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits autoprocessing of CASP1, CASP1-dependent IL1B secretion, PYCARD aggregation and PYCARD-mediated apoptosis but not apoptosis induced by FAS or BID. Displays anti-inflammatory activity. Required for immunity against C.albicans infection. Involved in the innate immune response by contributing to pro-inflammatory cytokine release in response to invasive bacterial infection. Contributes to T-cell-mediated inflammatory responses in the skin. Plays a role in protection against periodontitis through its involvement in induction of IL1A via ERK activation in oral epithelial cells infected with periodontal pathogens. Exhibits both ATPase and GTPase activities.

Subunit / interactions. Oligomerizes. Interacts with PYCARD. Also interacts with CASP1 and IL1B. Interacts with NOD1 and components of the NOD1 signaling pathway including RIPK2, NR2C2/TAK1 and IKBKG/NEMO.

Subcellular location. Cytoplasm. Cell membrane.

Tissue specificity. Highly expressed in basal and suprabasal epidermal cell layers with lower levels in dermal fibroblast cells (at protein level). Widely expressed with highest levels in heart, brain and skeletal muscle. Also expressed in liver, colon, dermis and epidermis. Little expression detected in myeloid cells or peripheral blood mononuclear cells.

Domain organisation. The pyrin and ATP-binding domains are required to elicit cytokine release following bacterial infection. The NACHT domain is required for inhibition of CASP1 autoprocessing.

Induction. By infection with the periodontal pathogens T.forsythia and F.nucleatum (at protein level).

Similarity. Belongs to the NLRP family.

RefSeq proteins (2): NP_001378887, NP_789791 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004020	DAPIN	Domain
IPR007111	NACHT_NTPase	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR041075	NOD1/2_WH	Domain
IPR050637	NLRP_innate_immun_reg	Family

Pfam: PF02758, PF05729, PF17779

UniProt features (19 total): helix 7, compositionally biased region 3, domain 2, turn 2, mutagenesis site 2, chain 1, region of interest 1, binding site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2M5V	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86W26-F1	74.06	0.27

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): 173–180

Mutagenesis-validated functional residues (2):

Position	Phenotype
179	reduced release of il8 following invasive bacterial infection.
252	reduced release of il8 following invasive bacterial infection.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_8_PRODUCTION, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_INTERLEUKIN_1_PRODUCTION, HATADA_METHYLATED_IN_LUNG_CANCER_DN, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_T_HELPER_1_TYPE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_T_HELPER_1_TYPE_IMMUNE_RESPONSE, GOBP_CYTOKINE_PRODUCTION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION

GO Biological Process (16): activation of innate immune response (GO:0002218), adaptive immune response (GO:0002250), positive regulation of T-helper 1 type immune response (GO:0002827), inflammatory response (GO:0006954), positive regulation of interleukin-1 alpha production (GO:0032730), positive regulation of interleukin-6 production (GO:0032755), positive regulation of interleukin-8 production (GO:0032757), innate immune response (GO:0045087), regulation of inflammatory response (GO:0050727), positive regulation of inflammatory response (GO:0050729), defense response to fungus (GO:0050832), positive regulation of defense response to bacterium (GO:1900426), positive regulation of T-helper 17 type immune response (GO:2000318), immune system process (GO:0002376), positive regulation of defense response (GO:0031349), positive regulation of immune response (GO:0050778)

GO Molecular Function (4): GTPase activity (GO:0003924), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166)

GO Cellular Component (7): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic side of plasma membrane (GO:0009898), nuclear membrane (GO:0031965), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
immune response	3
defense response	3
positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	2
positive regulation of cytokine production	2
inflammatory response	2
regulation of defense response	2
positive regulation of defense response	2
positive regulation of response to external stimulus	2
positive regulation of response to stimulus	2
ribonucleoside triphosphate phosphatase activity	2
activation of immune response	1
positive regulation of innate immune response	1
regulation of T-helper 1 type immune response	1
T-helper 1 type immune response	1
interleukin-1 alpha production	1
regulation of interleukin-1 alpha production	1
positive regulation of interleukin-1 production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
interleukin-8 production	1
regulation of interleukin-8 production	1
defense response to symbiont	1
regulation of response to external stimulus	1
regulation of inflammatory response	1
response to fungus	1
positive regulation of response to biotic stimulus	1
defense response to bacterium	1
regulation of defense response to bacterium	1
T-helper 17 type immune response	1
regulation of T-helper 17 type immune response	1
biological_process	1
positive regulation of immune system process	1
regulation of immune response	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ATP-dependent activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nuclear lumen	1

Protein interactions and networks

STRING

663 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NLRP10	NLRC4	Q9NPP4	769
NLRP10	CASP1	P29466	736
NLRP10	PYCARD	Q9ULZ3	720
NLRP10	BECN1	Q14457	715
NLRP10	AIM2	O14862	667
NLRP10	NLRP2	Q9NX02	554
NLRP10	NLRP1	Q9C000	549
NLRP10	NAIP	Q13075	516
NLRP10	FAF1	Q9UNN5	516
NLRP10	TNIP1	Q15025	506
NLRP10	PYDC1	Q8WXC3	492
NLRP10	NLRP12	P59046	454
NLRP10	OR10A3	P58181	448
NLRP10	CARD8	Q9Y2G2	436
NLRP10	IL18	Q14116	432

IntAct

8 interactions, top by confidence:

A	B	Type	Score
TBC1D22B	A2ML1	psi-mi:“MI:0914”(association)	0.530
NLRP10	HIST2H2BF	psi-mi:“MI:0915”(physical association)	0.400
M		psi-mi:“MI:0914”(association)	0.350
NLRP10	UBE4B	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): NLRP10 (Affinity Capture-MS), NLRP10 (Proximity Label-MS), NLRP10 (Affinity Capture-MS), STK26 (Affinity Capture-MS), NLRP10 (Affinity Capture-MS), ATG2B (Affinity Capture-MS), UBE4B (Affinity Capture-MS), NETO2 (Affinity Capture-MS), NLRP10 (Affinity Capture-MS), NLRP10 (Affinity Capture-Western), TRIM31 (Affinity Capture-Western), NLRP10 (Cross-Linking-MS (XL-MS)), NLRP10 (Affinity Capture-MS), NLRP10 (Two-hybrid), NLRP10 (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, A6QLE5, B0FPE9, D4A523, Q1MT80, Q2LKV2, Q86W26, Q8CCN1, Q8R4B8, Q96P20, Q9I9N6, A1Z198, A8Y3R9, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5R7, P10775, P13489, P29315, P59044, P59046, P59047, Q0GKD5, Q2LKU9, Q2LKV5, Q2LKW6, Q5RAV7, Q63035, Q6B966, Q86W24, Q86W25, Q8HXK9, Q8HZP9, Q91VI7, Q91WS2, Q9C000, Q9EPB4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

109 predictions. Top by Δscore:

Variant	Effect	Δscore
11:7963203:TCACC:T	donor_loss	1.0000
11:7963205:A:AC	donor_gain	1.0000
11:7963205:AC:A	donor_gain	1.0000
11:7963206:C:CC	donor_gain	1.0000
11:7963206:C:CT	donor_loss	1.0000
11:7963206:CC:C	donor_gain	1.0000
11:7963206:CCATG:C	donor_gain	1.0000
11:7963206:CCAT:C	donor_gain	0.9900
11:7963206:CCA:C	donor_gain	0.9800
11:7960997:A:C	acceptor_gain	0.9700
11:7961321:ATCT:A	acceptor_gain	0.9400
11:7961322:TCT:T	acceptor_gain	0.9300
11:7961324:T:A	acceptor_gain	0.9200
11:7961320:AATCT:A	acceptor_gain	0.9100
11:7963200:CACT:C	donor_loss	0.9100
11:7961323:C:A	acceptor_gain	0.9000
11:7963201:ACTC:A	donor_loss	0.9000
11:7963254:A:AC	donor_gain	0.8800
11:7963255:TG:T	donor_gain	0.8700
11:7961319:TAATC:T	acceptor_gain	0.8600
11:7961321:AT:A	acceptor_gain	0.8400
11:7963228:G:C	donor_gain	0.8400
11:7961323:C:CC	acceptor_gain	0.8300
11:7963256:G:T	donor_gain	0.8200
11:7961322:TCTGA:T	acceptor_loss	0.8100
11:7961323:C:CA	acceptor_loss	0.8100
11:7961334:A:T	acceptor_loss	0.7900
11:7963290:T:TA	donor_gain	0.7700
11:7960993:T:TA	acceptor_gain	0.7500
11:7960993:T:C	acceptor_gain	0.7300

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000885043 (11:7966593 T>C), RS1000998052 (11:7962903 C>T), RS1001050520 (11:7963253 C>T), RS1001637667 (11:7961651 G>T), RS1001974870 (11:7962608 C>G,T), RS1002142788 (11:7962453 G>A), RS1002284090 (11:7962240 T>C), RS1002791594 (11:7960033 A>C), RS1003538422 (11:7965281 C>T), RS1003711177 (11:7963895 T>A,C), RS1005068067 (11:7957649 G>A,T), RS1005173758 (11:7962467 A>T), RS1005185547 (11:7960733 C>T), RS1005354642 (11:7967314 A>G), RS1005391322 (11:7962631 T>C)

Disease associations

OMIM: gene MIM:609662 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001709_8	Atopic dermatitis	2.000000e-22
GCST003329_9	Response to anti-TNF therapy in rheumatoid arthritis	2.000000e-06
GCST010725_20	Malaria	4.000000e-69
GCST010725_33	Malaria	2.000000e-67
GCST010725_51	Malaria	1.000000e-55

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist

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

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium	increases expression, decreases expression, increases abundance	2
bisphenol A	decreases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
sodium arsenite	increases expression	1
tobacco tar	decreases reaction, increases expression	1
potassium chromate(VI)	increases expression	1
diallyl disulfide	increases expression, decreases reaction	1
nickel sulfate	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
Benzo(a)pyrene	increases methylation	1
Pentachlorophenol	affects expression	1
Sodium Dodecyl Sulfate	increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression, decreases reaction, increases expression, increases reaction	1
Cadmium Chloride	decreases expression, increases abundance	1
Okadaic Acid	affects expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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