NLRP10

protein-coding

NLR family pyrin domain containing 10, the group of Pyrin domain containing|NLR family

Gene summary

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. [provided by RefSeq, Jul 2008]

Previous symbols:

NALP10

MANE transcript

NM_001391958.1

Inheritance

—

ClinVar variants

U:103B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.91

Max pathogenic AF

—

Genomic locus

chr11:7,957,537-7,965,447

External References & Databases

Ensembl (ENSG00000182261)

Transcript & Mutation Effects

hg38 • Region Span ~7.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NLRP10 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 102

not providedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001391958.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar		3 clinvar	6
missense			100 clinvar	4 clinvar		104
nonsense						0
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)						0
Total	0	0	103	5	3	111

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001391958.1	RefSeq	NP_001378887.1	2	MANE Select
ENST00000691676.1	Ensembl	ENSP00000509542.1	2	MANE Select
NM_176821.4	RefSeq	NP_789791.1	2	Standard
ENST00000328600.3	Ensembl	ENSP00000327763.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Nucleotide-binding Oligomerization Domain (NOD) pathway

Biological Process

adaptive immune response
positive regulation of T-helper 1 type immune response
inflammatory response
innate immune response
positive regulation of interleukin-1 alpha secretion

Molecular Function

GTPase activity
ATP binding
ATPase activity

Cellular Component

cytoplasm
extrinsic component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000328600
Coding exons: 2
Length: 6003
Individuals with no LoFs: 125612
Homozygous LoFs: 0
Heterozygous LoFs: 134
Defined: 125746
p: 0.000533

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.287	362	347	1.04	0.0000189	4293
Missense (PolyPhen)		63	61.924	1.0174		914
Synonymous	-1.20	167	148	1.13	0.00000832	1277
Loss of Function	0.309	13	14.3	0.912	6.88e-7	185

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00043	0.00040	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.0029	0.0029	notable
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits autoprocessing of CASP1, CASP1-dependent IL1B secretion, PYCARD aggregation and PYCARD-mediated apoptosis but not apoptosis induced by FAS or BID (PubMed:15096476). Displays anti-inflammatory activity (PubMed:20393137). Required for immunity against C.albicans infection (By similarity). Involved in the innate immune response by contributing to proinflammatory cytokine release in response to invasive bacterial infection (PubMed:22672233). Contributes to T-cell-mediated inflammatory responses in the skin (By similarity). 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 (PubMed:28766990). Exhibits both ATPase and GTPase activities (PubMed:23861819). {ECO:0000250|UniProtKB:Q8CCN1, ECO:0000269|PubMed:15096476, ECO:0000269|PubMed:20393137, ECO:0000269|PubMed:22672233, ECO:0000269|PubMed:23861819}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.461
RVIS EVS: 0.05
RVIS percentile EVS: 57.52

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.682

Gene Damage Prediction

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