NLRP4
gene geneOn this page
Also known as PYPAF4FLJ32126PAN2RNH2CLR19.5CT58
Summary
NLRP4 (NLR family pyrin domain containing 4, HGNC:22943) is a protein-coding gene on chromosome 19q13.43, encoding NACHT, LRR and PYD domains-containing protein 4 (Q96MN2). May be involved in inflammation and recognition of cytosolic pathogen-associated molecular patterns (PAMPs) not intercepted by membrane-bound receptors.
The protein encoded by this gene is a member of the nucleotide-binding and leucine-rich repeat receptor (NLR) family, and is predicted to contain an N-terminal pyrin effector domain (PYD), a centrally-located nucleotide-binding and oligomerization domain (NACHT) and C-terminal leucine-rich repeats (LRR). This gene product has a demonstrated role as a negative regulator of autophagy and type I interferon signaling pathways as a result of protein interactions with its NACHT domain. The PYD domain has also been shown to be important in the inhibition of NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells).
Source: NCBI Gene 147945 — RefSeq curated summary.
At a glance
- GWAS associations: 1
- Clinical variants (ClinVar): 176 total
- Druggable target: yes
- MANE Select transcript:
NM_134444
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:22943 |
| Approved symbol | NLRP4 |
| Name | NLR family pyrin domain containing 4 |
| Location | 19q13.43 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | PYPAF4, FLJ32126, PAN2, RNH2, CLR19.5, CT58 |
| Ensembl gene | ENSG00000160505 |
| Ensembl biotype | protein_coding |
| OMIM | 609645 |
| Entrez | 147945 |
Gene structure
Transcript identifiers
Ensembl transcripts: 4 — 4 protein_coding
ENST00000301295, ENST00000587464, ENST00000587891, ENST00000589437
RefSeq mRNA: 1 — MANE Select: NM_134444
NM_134444
CCDS: CCDS12936
Canonical transcript exons
ENST00000301295 — 10 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001052721 | 55870827 | 55870997 |
| ENSE00001052724 | 55876996 | 55877166 |
| ENSE00001115563 | 55861992 | 55862159 |
| ENSE00001115570 | 55878794 | 55878964 |
| ENSE00001115573 | 55857674 | 55859249 |
| ENSE00001115576 | 55861386 | 55861547 |
| ENSE00001115579 | 55867709 | 55867876 |
| ENSE00001373388 | 55852016 | 55852360 |
| ENSE00001714943 | 55836540 | 55836934 |
| ENSE00002901863 | 55881470 | 55881855 |
Expression profiles
Bgee: expression breadth broad, 42 present calls, max score 100.00.
FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0884 / max 73.3754, expressed in 27 samples.
FANTOM5 promoters (3 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 177695 | 0.0687 | 20 |
| 208944 | 0.0116 | 6 |
| 177694 | 0.0081 | 1 |
Top tissues by expression
230 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| secondary oocyte | CL:0000655 | 100.00 | gold quality |
| oocyte | CL:0000023 | 99.97 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 86.76 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 84.72 | gold quality |
| sperm | CL:0000019 | 80.44 | gold quality |
| kidney epithelium | UBERON:0004819 | 74.68 | gold quality |
| epithelial cell of pancreas | CL:0000083 | 74.45 | gold quality |
| testis | UBERON:0000473 | 67.65 | gold quality |
| right testis | UBERON:0004534 | 67.22 | gold quality |
| left testis | UBERON:0004533 | 66.73 | gold quality |
| left ventricle myocardium | UBERON:0006566 | 56.68 | gold quality |
| lymph node | UBERON:0000029 | 56.26 | gold quality |
| cardiac muscle of right atrium | UBERON:0003379 | 54.94 | gold quality |
| adult organism | UBERON:0007023 | 54.02 | gold quality |
| upper arm skin | UBERON:0004263 | 53.52 | gold quality |
| quadriceps femoris | UBERON:0001377 | 53.18 | gold quality |
| vastus lateralis | UBERON:0001379 | 52.48 | gold quality |
| buccal mucosa cell | CL:0002336 | 52.45 | gold quality |
| pancreatic ductal cell | CL:0002079 | 52.17 | silver quality |
| myocardium | UBERON:0002349 | 51.55 | gold quality |
| vermiform appendix | UBERON:0001154 | 51.19 | gold quality |
| tonsil | UBERON:0002372 | 51.10 | gold quality |
| caecum | UBERON:0001153 | 48.68 | gold quality |
| deltoid | UBERON:0001476 | 48.29 | gold quality |
| layer of synovial tissue | UBERON:0007616 | 48.14 | gold quality |
| tibialis anterior | UBERON:0001385 | 47.74 | silver quality |
| inferior vagus X ganglion | UBERON:0005363 | 47.23 | gold quality |
| ileal mucosa | UBERON:0000331 | 47.11 | silver quality |
| tendon of biceps brachii | UBERON:0008188 | 47.06 | gold quality |
| nasal cavity epithelium | UBERON:0005384 | 47.03 | gold quality |
Single-cell (SCXA)
Detected in 2 experiment(s), a significant marker in 2.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-MTAB-3929 | yes | 1982.89 |
| E-ANND-3 | yes | 3.60 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
31 targeting NLRP4, 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-548AJ-3P | 99.96 | 73.38 | 5345 |
| HSA-MIR-548X-3P | 99.96 | 73.38 | 5345 |
| HSA-MIR-548J-3P | 99.94 | 72.61 | 4881 |
| HSA-MIR-548AE-3P | 99.93 | 72.66 | 4867 |
| HSA-MIR-548AH-3P | 99.93 | 72.54 | 4872 |
| HSA-MIR-548AM-3P | 99.93 | 72.54 | 4872 |
| HSA-MIR-548AQ-3P | 99.93 | 72.66 | 4867 |
| HSA-MIR-5680 | 99.91 | 69.83 | 3421 |
| HSA-MIR-4493 | 99.90 | 66.48 | 977 |
| HSA-MIR-6499-3P | 99.90 | 66.38 | 1212 |
| HSA-MIR-548D-3P | 99.87 | 70.67 | 4362 |
| HSA-MIR-548BB-3P | 99.86 | 70.58 | 4354 |
| HSA-MIR-548AC | 99.84 | 70.77 | 4351 |
| HSA-MIR-548H-3P | 99.84 | 70.80 | 4349 |
| HSA-MIR-548Z | 99.84 | 70.80 | 4349 |
| HSA-MIR-497-3P | 99.61 | 69.71 | 1990 |
| HSA-MIR-4762-5P | 99.57 | 68.54 | 1424 |
| HSA-MIR-4276 | 99.56 | 67.66 | 2514 |
| HSA-MIR-6733-3P | 99.54 | 67.80 | 1281 |
| HSA-MIR-5190 | 99.15 | 67.76 | 1234 |
| HSA-MIR-4664-5P | 98.17 | 65.07 | 1020 |
| HSA-MIR-1285-5P | 98.01 | 68.71 | 779 |
| HSA-MIR-6742-3P | 97.95 | 64.50 | 1490 |
| HSA-MIR-3665 | 97.73 | 65.08 | 975 |
| HSA-MIR-3121-5P | 97.30 | 66.62 | 1146 |
| HSA-MIR-5194 | 96.77 | 63.91 | 1021 |
| HSA-MIR-339-5P | 96.73 | 66.01 | 820 |
| HSA-MIR-6738-5P | 96.33 | 63.61 | 815 |
| HSA-MIR-6734-5P | 95.70 | 65.56 | 950 |
| HSA-MIR-1914-3P | 95.07 | 63.37 | 762 |
Literature-anchored findings (GeneRIF, showing 11)
- NLRP4 is recruited to and accumulates in bacteria-containing phagosomes and transiently dissociates from beclin1 following group A streptococcus infection, thereby controlling the autophagic flux crucial for cell-autonomous antibacterial resistance. (PMID:21209283)
- Our results provide molecular insight into the mechanisms by which NLRP4-DTX4 targets TBK1 for degradation. (PMID:22388039)
- Structural and functional analysis of the NLRP4 pyrin domain. (PMID:22928810)
- Findings suggest that NLR family pyrin domain containing 2 (NLRP2P) is a processed pseudogene that regulates NF-kappaB RelA/p65 activity and thus represents the newest member of the POP family, pyrin-only protein 4 (POP4; NLRP4). (PMID:24871464)
- This study describes conformational stability of native NLRP14 and mutants in their monomeric and dimeric states and compares them to NLRP4, a representative of a native pyrin domain fold. (PMID:25403012)
- NLRP4 is an important mediator of cardiac remodeling in vitro and in vivo. (PMID:28486191)
- NLRP4 binds ARHGDIA (Rho GDP dissociation inhibitor alpha) to regulate Rho GTPase signaling and facilitate actin-mediated xenophagy. (PMID:29099277)
- The minor allele of rs16986718G > A in NLRP4 may be a genetic marker that predicts asthma exacerbation in adult asthmatics who smoke. (PMID:30526007)
- Somatic Mutation of NLRP Genes in Gastric and Colonic Cancers. (PMID:34257569)
- NLRP4 negatively regulates type I interferon response and influences the outcome in anti-programmed cell death protein (PD)-1/PD-ligand 1 therapy. (PMID:34927309)
- The hyper-expression of NLRP4 characterizes the occurrence of macrophage activation syndrome assessing STING pathway in adult-onset Still’s disease. (PMID:35467709)
Cross-species orthologs
10 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| mus_musculus | Nlrp4f | ENSMUSG00000032999 |
| mus_musculus | Nlrp4b | ENSMUSG00000034087 |
| mus_musculus | Nlrp4c | ENSMUSG00000034690 |
| mus_musculus | Nlrp4a | ENSMUSG00000040601 |
| mus_musculus | Nlrp4e | ENSMUSG00000045693 |
| rattus_norvegicus | Nlrp4b | ENSRNOG00000015527 |
| rattus_norvegicus | Nlrp4 | ENSRNOG00000021996 |
| rattus_norvegicus | Nlrp4f | ENSRNOG00000027705 |
| rattus_norvegicus | Nlrp4a | ENSRNOG00000042030 |
| rattus_norvegicus | Nlrp4al1 | ENSRNOG00000059733 |
Paralogs (20): NLRP2 (ENSG00000022556), NLRP1 (ENSG00000091592), NOD1 (ENSG00000106100), NLRC5 (ENSG00000140853), NLRP12 (ENSG00000142405), NLRP14 (ENSG00000158077), NLRX1 (ENSG00000160703), NLRP3 (ENSG00000162711), NOD2 (ENSG00000167207), NLRP7 (ENSG00000167634), NLRC3 (ENSG00000167984), NLRP5 (ENSG00000171487), NLRP13 (ENSG00000173572), NLRP6 (ENSG00000174885), CIITA (ENSG00000179583), NLRP8 (ENSG00000179709), NLRP11 (ENSG00000179873), NLRP10 (ENSG00000182261), NLRP9 (ENSG00000185792), PYDC2 (ENSG00000253548)
Protein
Protein identifiers
NACHT, LRR and PYD domains-containing protein 4 — Q96MN2 (reviewed: Q96MN2)
Alternative names: Cancer/testis antigen 58, PAAD and NACHT-containing protein 2, PYRIN and NACHT-containing protein 2, PYRIN-containing APAF1-like protein 4, Ribonuclease inhibitor 2
All UniProt accessions (3): Q96MN2, K7ES09, K7ESK5
UniProt curated annotations — full annotation on UniProt →
Function. May be involved in inflammation and recognition of cytosolic pathogen-associated molecular patterns (PAMPs) not intercepted by membrane-bound receptors. Acts as a negative regulator of the type I interferon signaling pathway by serving as an adapter to promote DTX4-mediated ubiquitination of activated TBK1, and its subsequent degradation. Suppresses NF-kappaB induction by the cytokines TNFA and IL1B, suggesting that it operates at a point of convergence in these two cytokine signaling pathways.
Subunit / interactions. Interacts with CHUK/IKKA, inhibiting its kinase activity.
Domain organisation. The pyrin domain is sufficient for suppression of NF-kappaB activity, it adopts a typical death domain fold, but in contrast to several NLRP family pyrin domains it doesn’t bind homotypically to the ASC adapter, which supports the observation that NLRP4 has no effect on IL1B activation.
Similarity. Belongs to the NLRP family.
Isoforms (3)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q96MN2-1 | 1 | yes |
| Q96MN2-2 | 2 | |
| Q96MN2-3 | 3 |
RefSeq proteins (1): NP_604393* (*=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 (32 total): repeat 8, sequence conflict 7, sequence variant 6, helix 5, domain 2, splice variant 2, chain 1, binding site 1
Structure
Experimental structures (PDB)
1 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 4EWI | X-RAY DIFFRACTION | 2.28 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q96MN2-F1 | 89.08 | 0.66 |
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): 155–162
Function
Pathways and Gene Ontology
Reactome pathways
8 pathways
| ID | Pathway |
|---|---|
| R-HSA-1606341 | IRF3 mediated activation of type 1 IFN |
| R-HSA-3134975 | Regulation of innate immune responses to cytosolic DNA |
| R-HSA-3270619 | IRF3-mediated induction of type I IFN |
| R-HSA-1606322 | ZBP1(DAI) mediated induction of type I IFNs |
| R-HSA-168249 | Innate Immune System |
| R-HSA-168256 | Immune System |
| R-HSA-1834941 | STING mediated induction of host immune responses |
| R-HSA-1834949 | Cytosolic sensors of pathogen-associated DNA |
MSigDB gene sets: 64 (showing top):
REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_NEGATIVE_REGULATION_OF_DEFENSE_RESPONSE, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, AFFAR_YY1_TARGETS_DN, GOBP_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_DEFENSE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS
GO Biological Process (7): inflammatory response (GO:0006954), negative regulation of innate immune response (GO:0045824), regulation of inflammatory response (GO:0050727), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), protein K48-linked ubiquitination (GO:0070936), antiviral innate immune response (GO:0140374), protein K33-linked deubiquitination (GO:1990168)
GO Molecular Function (4): ATP binding (GO:0005524), molecular adaptor activity (GO:0060090), nucleotide binding (GO:0000166), protein binding (GO:0005515)
GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)
Reactome top-level categories
Rollup of top-5 pathways:
| Category | Pathways |
|---|---|
| Cytosolic sensors of pathogen-associated DNA | 3 |
| ZBP1(DAI) mediated induction of type I IFNs | 1 |
| STING mediated induction of host immune responses | 1 |
| Immune System | 1 |
| Innate Immune System | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| innate immune response | 2 |
| binding | 2 |
| cellular anatomical structure | 2 |
| defense response | 1 |
| negative regulation of response to biotic stimulus | 1 |
| negative regulation of defense response | 1 |
| negative regulation of response to external stimulus | 1 |
| regulation of innate immune response | 1 |
| negative regulation of immune response | 1 |
| inflammatory response | 1 |
| regulation of defense response | 1 |
| regulation of response to external stimulus | 1 |
| ubiquitin-dependent protein catabolic process | 1 |
| proteasomal protein catabolic process | 1 |
| protein polyubiquitination | 1 |
| defense response to virus | 1 |
| protein deubiquitination | 1 |
| adenyl ribonucleotide binding | 1 |
| purine ribonucleoside triphosphate binding | 1 |
| molecular_function | 1 |
| nucleoside phosphate binding | 1 |
| heterocyclic compound binding | 1 |
| intracellular anatomical structure | 1 |
| cytoplasm | 1 |
Protein interactions and networks
STRING
619 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| NLRP4 | BECN1 | Q14457 | 986 |
| NLRP4 | DTX4 | Q9Y2E6 | 983 |
| NLRP4 | AIM2 | O14862 | 860 |
| NLRP4 | NLRP3 | Q96P20 | 854 |
| NLRP4 | NLRP1 | Q9C000 | 792 |
| NLRP4 | MEFV | O15553 | 761 |
| NLRP4 | NLRP12 | P59046 | 758 |
| NLRP4 | NLRC4 | Q9NPP4 | 754 |
| NLRP4 | PYCARD | Q9ULZ3 | 742 |
| NLRP4 | CASP1 | P29466 | 714 |
| NLRP4 | NLRP7 | Q8WX94 | 698 |
| NLRP4 | NLRP2 | Q9NX02 | 691 |
| NLRP4 | TBK1 | Q9UHD2 | 640 |
| NLRP4 | NLRP6 | P59044 | 570 |
| NLRP4 | NOD1 | Q9Y239 | 541 |
IntAct
4 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| NLRP4 | SUGT1 | psi-mi:“MI:0915”(physical association) | 0.400 |
| NLRP4 | PYDC2 | psi-mi:“MI:0915”(physical association) | 0.370 |
| ATG16L1 | ESYT2 | psi-mi:“MI:0914”(association) | 0.350 |
BioGRID (11): NLRP4 (Co-fractionation), NLRP4 (Affinity Capture-Western), NLRP4 (Affinity Capture-Western), NLRP4 (Affinity Capture-MS), NLRP4 (Affinity Capture-MS), NLRP4 (Affinity Capture-Western), TBK1 (Affinity Capture-Western), NLRP4 (Affinity Capture-Western), HSP90AA1 (Affinity Capture-Western), SUGT1 (Affinity Capture-Western), NLRP4 (Affinity Capture-Western)
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: A0A2H5Q1B8, P59046, Q6Q4D0, Q96MN2, A0A386CAB9, A1Z198, A6QLE5, B0FPE9, D4A523, D9I2F9, D9I2G1, D9I2G3, D9I2G4, D9I2H0, E9Q5R7, O15553, P10775, P13489, P29315, P59044, P59045, Q0GKD5, Q288C4, Q2LKU9, Q2LKV2, Q2LKV5, Q2LKW6, Q3TKR3, Q63035, Q647I9, Q66X01, Q66X03, Q66X19, Q6B966, Q7RTR0, Q86W24, Q86W25, Q86W26, Q86W28, Q8BU40
SIGNOR signaling
0 interactions.
Disease & clinical
Clinical variants and AI predictions
ClinVar
176 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 134 |
| Likely benign | 16 |
| Benign | 2 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
1690 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 19:55859250:G:GG | donor_gain | 1.0000 |
| 19:55861990:A:AG | acceptor_gain | 1.0000 |
| 19:55861991:G:GG | acceptor_gain | 1.0000 |
| 19:55861991:GA:G | acceptor_gain | 1.0000 |
| 19:55861991:GAATA:G | acceptor_gain | 1.0000 |
| 19:55862155:CTAGC:C | donor_gain | 1.0000 |
| 19:55862158:GC:G | donor_gain | 1.0000 |
| 19:55862160:G:GG | donor_gain | 1.0000 |
| 19:55867877:G:GG | donor_gain | 1.0000 |
| 19:55870823:ATAG:A | acceptor_gain | 1.0000 |
| 19:55870825:A:AG | acceptor_gain | 1.0000 |
| 19:55870825:AG:A | acceptor_gain | 1.0000 |
| 19:55870825:AGGTT:A | acceptor_gain | 1.0000 |
| 19:55870826:G:GG | acceptor_gain | 1.0000 |
| 19:55870826:GG:G | acceptor_gain | 1.0000 |
| 19:55870826:GGT:G | acceptor_gain | 1.0000 |
| 19:55870826:GGTT:G | acceptor_gain | 1.0000 |
| 19:55870826:GGTTG:G | acceptor_gain | 1.0000 |
| 19:55870995:GTG:G | donor_gain | 1.0000 |
| 19:55876994:AGTTT:A | acceptor_gain | 1.0000 |
| 19:55876995:GTTTG:G | acceptor_gain | 1.0000 |
| 19:55836731:G:GG | donor_gain | 0.9900 |
| 19:55840899:A:AG | acceptor_gain | 0.9900 |
| 19:55852107:T:TA | acceptor_gain | 0.9900 |
| 19:55852350:G:GT | donor_gain | 0.9900 |
| 19:55855425:A:T | donor_gain | 0.9900 |
| 19:55855432:G:GT | donor_gain | 0.9900 |
| 19:55857657:T:A | acceptor_gain | 0.9900 |
| 19:55857664:A:AG | acceptor_gain | 0.9900 |
| 19:55857664:ACT:A | acceptor_gain | 0.9900 |
AlphaMissense
6602 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 19:55852161:A:C | K27N | 0.996 |
| 19:55852161:A:T | K27N | 0.996 |
| 19:55858741:T:C | F450L | 0.989 |
| 19:55858742:T:C | F450S | 0.989 |
| 19:55858743:C:A | F450L | 0.989 |
| 19:55858743:C:G | F450L | 0.989 |
| 19:55852133:T:C | L18P | 0.987 |
| 19:55857937:T:C | F182L | 0.986 |
| 19:55857939:C:A | F182L | 0.986 |
| 19:55857939:C:G | F182L | 0.986 |
| 19:55852169:T:C | L30P | 0.985 |
| 19:55858601:C:A | A403D | 0.985 |
| 19:55858633:T:C | F414L | 0.985 |
| 19:55858635:T:A | F414L | 0.985 |
| 19:55858635:T:G | F414L | 0.985 |
| 19:55867789:T:C | L756P | 0.985 |
| 19:55857875:A:T | K161I | 0.984 |
| 19:55858076:T:C | F228S | 0.984 |
| 19:55858634:T:C | F414S | 0.984 |
| 19:55852157:T:C | F26S | 0.983 |
| 19:55852160:A:T | K27I | 0.983 |
| 19:55852133:T:A | L18H | 0.982 |
| 19:55858761:G:C | Q456H | 0.982 |
| 19:55858761:G:T | Q456H | 0.982 |
| 19:55858768:T:C | C459R | 0.982 |
| 19:55857856:G:A | G155R | 0.981 |
| 19:55857856:G:C | G155R | 0.981 |
| 19:55858507:T:G | Y372D | 0.981 |
| 19:55870839:C:G | C789W | 0.981 |
| 19:55852323:A:C | R81S | 0.980 |
dbSNP variants (sampled 300 via entrez): RS1000002806 (19:55854826 G>A), RS1000045768 (19:55878635 C>A), RS1000056240 (19:55873316 G>A), RS1000104138 (19:55839938 C>T), RS1000109631 (19:55873033 T>C), RS1000237096 (19:55868778 T>C), RS1000241939 (19:55837339 G>A), RS1000340965 (19:55863752 G>A), RS1000412518 (19:55850779 G>A), RS1000456821 (19:55864029 A>G), RS1000587522 (19:55845891 T>C), RS1000640507 (19:55854572 A>G), RS1000643681 (19:55879850 T>A), RS1000682626 (19:55841154 T>A), RS1000713400 (19:55840967 G>A,T)
Disease associations
OMIM: gene MIM:609645 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
1 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST008369_18 | Plasma anti-thyroglobulin levels | 9.000000e-07 |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL5465345 (SINGLE PROTEIN)
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
5 total (human), top 5 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| propionaldehyde | decreases expression | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| abrine | increases expression | 1 |
| theaflavin-3,3’-digallate | affects expression | 1 |
| Permethrin | increases expression | 1 |
ChEMBL screening assays
1 unique, capped per target: 1 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL5374772 | Binding | Inhibition of NLRP4 inflammasome activation in human PBMC assessed as reduction in IL-1beta secretion at 3 nM preincubated with LPS for 2.5 hrs followed by compound addition for 30 mins by ELISA | Discovery of Clinical Candidate NT-0796, a Brain-Penetrant and Highly Potent NLRP3 Inflammasome Inhibitor for Neuroinflammatory Disorders. — J Med Chem |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.