NLRP1

Chr 17p13

NLR family pyrin domain containing 1

Aliases:: KIAA0926, DKFZp586O1822, CARD7, NAC, CLR17.1
MANE:: ENST00000572272.6

OMIM: 606636 ↗NCBI: 22861 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

NLRP1 · Q9C000

v62025-08-01

Predicted Aligned Error matrix for NLRP1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

68.3/ 100

Low

1,473 residues

Confidence breakdown

Very high(≥ 90)17%
Confident(70–90)47%
Low(50–70)8%
Very low(< 50)28%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

COVID-19 research
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Primary immunodeficiency or monogenic inflammatory bowel disease
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Rare genetic inflammatory skin disorders
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Ductal plate malformation
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Disease associations (Open Targets)

corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome
0.74
autoinflammation with arthritis and dyskeratosis
0.67
Corneal intraepithelial dyskeratosis with palmoplantar hyperkeratosis and laryngeal dyskeratosis
0.64
respiratory papillomatosis, juvenile recurrent, congenital
0.46
vitiligo
0.39
DNA methylation
0.27
eye disorder
0.27
migraine disorder
0.26
digestive system neoplasm
0.23
Chorioretinal scar
0.22

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

NACHT, LRR and PYD domains-containing protein 1

Acts as the sensor component of the NLRP1 inflammasome, which mediates inflammasome activation in response to various pathogen-associated signals, leading to subsequent pyroptosis (PubMed:12191486, PubMed:17349957, PubMed:22665479, PubMed:27662089, PubMed:31484767, PubMed:33093214, PubMed:33410748, PubMed:33731929, PubMed:33731932, PubMed:35857590). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed:12191486, PubMed:17349957, PubMed:22665479). Acts as a recognition receptor (PRR): recognizes specific pathogens and other damage-associated signals, such as cleavage by some human enteroviruses and rhinoviruses, double-stranded RNA, UV-B irradiation, or Val-boroPro inhibitor, and mediates the formation of the inflammasome polymeric complex composed of NLRP1, CASP1 and PYCARD/ASC (PubMed:12191486, PubMed:17349957, PubMed:22665479, PubMed:25562666, PubMed:30096351, PubMed:30291141, PubMed:33093214, PubMed:33243852, PubMed:33410748, PubMed:35857590). In response to pathogen-associated signals, the N-terminal part of NLRP1 is degraded by the proteasome, releasing the cleaved C-terminal part of the protein (NACHT, LRR and PYD domains-containing protein 1, C-terminus), which polymerizes and associates with PYCARD/ASC to initiate the formation of the inflammasome complex: the NLRP1 inflammasome recruits pro-caspase-1 (proCASP1) and promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), leading to pyroptosis (PubMed:12191486, PubMed:17349957, PubMed:22665479, PubMed:32051255, PubMed:33093214). In the absence of GSDMD expression, the NLRP1 inflammasome is able to recruit and activate CASP8, leading to activation of gasdermin-E (GSDME) (PubMed:33852854, PubMed:35594856). Activation of NLRP1 inflammasome is also required for HMGB1 secretion; the active cytokines and HMGB1 stimulate inflammatory responses (PubMed:22801494). Binds ATP and shows ATPase activity (PubMed:11113115, PubMed:15212762, PubMed:33243852). Plays an important role in antiviral immunity and inflammation in the human airway epithelium (PubMed:33093214). Specifically recognizes a number of pathogen-associated signals: upon infection by human rhinoviruses 14 and 16 (HRV-14 and HRV-16), NLRP1 is cleaved and activated which triggers NLRP1-dependent inflammasome activation and IL18 secretion (PubMed:33093214). Positive-strand RNA viruses, such as Semliki forest virus and long dsRNA activate the NLRP1 inflammasome, triggering IL1B release in a NLRP1-dependent fashion (PubMed:33243852). Acts as a direct sensor for long dsRNA and thus RNA virus infection (PubMed:33243852). May also be activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, in a NOD2-dependent manner (PubMed:18511561). The NLRP1 inflammasome is also activated in response to UV-B irradiation causing ribosome collisions: ribosome collisions cause phosphorylation and activation of NLRP1 in a MAP3K20-dependent manner, leading to pyroptosis (PubMed:35857590)