NLRC4 Gene

HGNC Family NLR family (NLR)
Name NLR family, CARD domain containing 4
Description This gene encodes a member of the caspase recruitment domain-containing NLR family. Family members play essential roles in innate immune response to a wide range of pathogenic organisms, tissue damage and other cellular stresses. Mutations in this gene result in autoinflammation with infantile enterocolitis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNLRC4 is a cytosolic receptor that plays a central role in innate immunity by sensing distinct bacterial products—most notably flagellin and type‐III secretion system rod or needle proteins—and, in cooperation with NAIP proteins, assembling into an inflammasome that activates caspase‑1. This activation leads to the processing and secretion of key proinflammatory cytokines (such as IL‑1β and IL‑18) and induces pyroptotic cell death, thereby restricting intracellular pathogens like Legionella, Klebsiella, Pseudomonas, and Salmonella. Importantly, NLRC4’s contribution to antimicrobial defense can be cell type–dependent, as studies in human macrophages show robust NLRC4 activation while certain epithelial cells preferentially use alternative pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and regulatory studies have further refined our understanding of NLRC4 inflammasome assembly. High‐resolution imaging reveals that NLRC4, via its caspase recruitment domain (CARD), polymerizes into defined helical structures that provide a platform for caspase‑1 recruitment. In parallel, NLRC4 expression and activity are modulated by several factors including p53, specific lncRNAs, and regulatory proteins such as PKCδ and HSC70—all of which can alter the kinetics or threshold for downstream caspase activation. These insights underscore that NLRC4 is not a mere on–off switch but a finely tuned sensor whose assembly is governed by both its intrinsic oligomerization properties and extrinsic modulatory signals."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDysregulation of NLRC4—whether through gain‐of‐function mutations or aberrant activation—can precipitate pathological inflammation across a range of conditions. Genetic alterations that lead to its constitutive activation are linked to autoinflammatory syndromes (including familial cold autoinflammatory syndrome and neonatal enterocolitis), while aberrant NLRC4 activity also contributes to inflammatory damage in metabolic diseases (e.g. diabetic nephropathy) and modulates cancer progression (as seen in breast cancer and glioma). Moreover, NLRC4 variants may influence susceptibility to infections such as HIV and modulate chronic inflammatory or autoimmune conditions including multiple sclerosis, psoriasis, and rheumatoid arthritis, with additional emerging roles in tissue homeostasis (for example in premature rupture of membranes) and in fine‐tuning immune responses during pulmonary infections and beyond."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yue Zhao, Jieling Yang, Jianjin Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The NLRC4 inflammasome receptors for bacterial flagellin and type III secretion apparatus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature10510"}], "href": "https://doi.org/10.1038/nature10510"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21918512"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21918512"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Els F Halff, Christoph A Diebolder, Marian Versteeg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Formation and structure of a NAIP5-NLRC4 inflammasome induced by direct interactions with conserved N- and C-terminal regions of flagellin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.393512"}], "href": "https://doi.org/10.1074/jbc.M112.393512"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23012363"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23012363"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Maya Vinzing, Julia Eitel, Juliane Lippmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NAIP and Ipaf control Legionella pneumophila replication in human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.180.10.6808"}], "href": "https://doi.org/10.4049/jimmunol.180.10.6808"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18453601"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18453601"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shanshan Cai, Sanjay Batra, Nobuko Wakamatsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NLRC4 inflammasome-mediated production of IL-1β modulates mucosal immunity in the lung against gram-negative bacterial infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1200195"}], "href": "https://doi.org/10.4049/jimmunol.1200195"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22547706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22547706"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Teddy Grandjean, Anne Boucher, Marion Thepaut, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The human NAIP-NLRC4-inflammasome senses the Pseudomonas aeruginosa T3SS inner-rod protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Immunol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/intimm/dxx047"}], "href": "https://doi.org/10.1093/intimm/dxx047"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28992059"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28992059"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jason S Damiano, Ruchi M Newman, John C Reed "}, {"type": "b", "children": [{"type": "t", "text": "Multiple roles of CLAN (caspase-associated recruitment domain, leucine-rich repeat, and NAIP CIIA HET-E, and TP1-containing protein) in the mammalian innate immune response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.173.10.6338"}], "href": "https://doi.org/10.4049/jimmunol.173.10.6338"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15528373"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15528373"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Nawar Naseer, Jenna Zhang, Renate Bauer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Salmonella enterica Serovar Typhimurium Induces NAIP/NLRC4- and NLRP3/ASC-Independent, Caspase-4-Dependent Inflammasome Activation in Human Intestinal Epithelial Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Infect Immun (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/iai.00663-21"}], "href": "https://doi.org/10.1128/iai.00663-21"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35678562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35678562"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Yang Li, Tian-Min Fu, Alvin Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1810524115"}], "href": "https://doi.org/10.1073/pnas.1810524115"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30279182"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30279182"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Subhashini Sadasivam, Sanjeev Gupta, Vegesna Radha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Caspase-1 activator Ipaf is a p53-inducible gene involved in apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1208201"}], "href": "https://doi.org/10.1038/sj.onc.1208201"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15580302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15580302"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Akhouri Kishore Raghawan, Anand Sripada, Gayathri Gopinath, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Disease-associated Mutant of NLRC4 Shows Enhanced Interaction with SUG1 Leading to Constitutive FADD-dependent Caspase-8 Activation and Cell Death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.763979"}], "href": "https://doi.org/10.1074/jbc.M116.763979"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27974463"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27974463"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Pilar Samperio Ventayol, Petra Geiser, Maria Letizia Di Martino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bacterial detection by NAIP/NLRC4 elicits prompt contractions of intestinal epithelial cell layers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2013963118"}], "href": "https://doi.org/10.1073/pnas.2013963118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33846244"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33846244"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ali Can Sahillioğlu, Nesrin Özören "}, {"type": "b", "children": [{"type": "t", "text": "Artificial Loading of ASC Specks with Cytosolic Antigens."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0134912"}], "href": "https://doi.org/10.1371/journal.pone.0134912"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26258904"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26258904"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Xiurong Wu, Zhang-Hua Yang, Jianfeng Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ribosome-rescuer PELO catalyzes the oligomeric assembly of NOD-like receptor family proteins via activating their ATPase enzymatic activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunity (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.immuni.2023.02.014"}], "href": "https://doi.org/10.1016/j.immuni.2023.02.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36948192"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36948192"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Andrew D Graustein, William R Berrington, Kati J Buckingham, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inflammasome Genetic Variants, Macrophage Function, and Clinical Outcomes in Cystic Fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2020-0257OC"}], "href": "https://doi.org/10.1165/rcmb.2020-0257OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33848452"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33848452"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Neil Romberg, Khatoun Al Moussawi, Carol Nelson-Williams, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.3066"}], "href": "https://doi.org/10.1038/ng.3066"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25217960"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25217960"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Akiko Kitamura, Yuki Sasaki, Takaya Abe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An inherited mutation in NLRC4 causes autoinflammation in human and mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20141091"}], "href": "https://doi.org/10.1084/jem.20141091"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25385754"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25385754"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Ryan Kolb, Liem Phan, Nicholas Borcherding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Obesity-associated NLRC4 inflammasome activation drives breast cancer progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms13007"}], "href": "https://doi.org/10.1038/ncomms13007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27708283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27708283"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Fang Yuan, Ryan Kolb, Gaurav Pandey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of the NLRC4-Inflammasome in Diabetic Nephropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0164135"}], "href": "https://doi.org/10.1371/journal.pone.0164135"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27706238"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27706238"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Raphaela P Semper, Michael Vieth, Markus Gerhard, et al. "}, {"type": "b", "children": [{"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Helicobacter pylori"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Exploits the NLRC4 Inflammasome to Dampen Host Defenses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1900351"}], "href": "https://doi.org/10.4049/jimmunol.1900351"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31511355"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31511355"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Hana Jin, Hye Jung Kim "}, {"type": "b", "children": [{"type": "t", "text": "NLRC4, ASC and Caspase-1 Are Inflammasome Components that Are Mediated by P2Y"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "2"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": "R Activation in Breast Cancer Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms21093337"}], "href": "https://doi.org/10.3390/ijms21093337"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32397236"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32397236"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Jaejoon Lim, Min Jun Kim, YoungJoon Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulation of the NLRC4 inflammasome contributes to poor prognosis in glioma patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-44261-9"}], "href": "https://doi.org/10.1038/s41598-019-44261-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31133717"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31133717"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Junichiro Hiruma, Kazutoshi Harada, Akira Motoyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Key component of inflammasome, NLRC4, was identified in the lesional epidermis of psoriatic patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dermatol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/1346-8138.14478"}], "href": "https://doi.org/10.1111/1346-8138.14478"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29797527"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29797527"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Reza Mahvelati Shamsabadi, Soroush Basafa, Reza Yarahmadi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elevated expression of NLRP1 and IPAF are related to oral pemphigus vulgaris pathogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Inflammation (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10753-014-0023-y"}], "href": "https://doi.org/10.1007/s10753-014-0023-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25342284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25342284"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Shruthi Ravimohan, Pholo Maenetje, Sara C Auld, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Common NLRC4 Gene Variant Associates With Inflammation and Pulmonary Function in Human Immunodeficiency Virus and Tuberculosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Infect Dis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cid/ciz898"}], "href": "https://doi.org/10.1093/cid/ciz898"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31751447"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31751447"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "JeongMin Sim, JeongMan Park, Suwan Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of Tim-3/Gal-9 Axis with NLRC4 Inflammasome in Glioma Malignancy: Tim-3/Gal-9 Induce the NLRC4 Inflammasome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms23042028"}], "href": "https://doi.org/10.3390/ijms23042028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35216164"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35216164"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Cristina Delgado-Arévalo, Marta Calvet-Mirabent, Ana Triguero-Martínez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NLRC4-mediated activation of CD1c+ DC contributes to perpetuation of synovitis in rheumatoid arthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JCI Insight (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/jci.insight.152886"}], "href": "https://doi.org/10.1172/jci.insight.152886"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36194479"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36194479"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Jaine Ls Soares, Enedina Ml Oliveira, Alessandra Pontillo "}, {"type": "b", "children": [{"type": "t", "text": "Variants in NLRP3 and NLRC4 inflammasome associate with susceptibility and severity of multiple sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mult Scler Relat Disord (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.msard.2019.01.023"}], "href": "https://doi.org/10.1016/j.msard.2019.01.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30658261"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30658261"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Alessandra Pontillo, Telma M Oshiro, Martina Girardelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in inflammasome' genes and susceptibility to HIV-1 infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Acquir Immune Defic Syndr (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/QAI.0b013e3182392ebe"}], "href": "https://doi.org/10.1097/QAI.0b013e3182392ebe"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22227487"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22227487"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Azadeh Askari, Reza Nosratabadi, Mehdi Khaleghinia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evaluation of NLRC4, NLRP1, and NLRP3, as Components of Inflammasomes, in Chronic Hepatitis B Virus-Infected Patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Viral Immunol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/vim.2016.0045"}], "href": "https://doi.org/10.1089/vim.2016.0045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27750030"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27750030"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Jinming Zhu, Chunling Ma, Lina Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A role for the NLRC4 inflammasome in premature rupture of membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0237847"}], "href": "https://doi.org/10.1371/journal.pone.0237847"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32833985"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32833985"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Akhouri Kishore Raghawan, Rajashree Ramaswamy, Vegesna Radha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HSC70 regulates cold-induced caspase-1 hyperactivation by an autoinflammation-causing mutant of cytoplasmic immune receptor NLRC4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1905261116"}], "href": "https://doi.org/10.1073/pnas.1905261116"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31597739"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31597739"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Li Liu, Christina Chan "}, {"type": "b", "children": [{"type": "t", "text": "IPAF inflammasome is involved in interleukin-1β production from astrocytes, induced by palmitate; implications for Alzheimer's Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Aging (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neurobiolaging.2013.08.016"}], "href": "https://doi.org/10.1016/j.neurobiolaging.2013.08.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24054992"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24054992"}]}]}]}
Synonyms CARD12, CLANB, CLAN1, AIFEC, CLANA, CLR2.1, CLANC, CLAN, CLAND, FCAS4, IPAF
Proteins NLRC4_HUMAN
NCBI Gene ID 58484
API
Download Associations
Predicted Functions View NLRC4's ARCHS4 Predicted Functions.
Co-expressed Genes View NLRC4's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View NLRC4's ARCHS4 Predicted Functions.

Functional Associations

NLRC4 has 5,087 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 100 datasets.

Click the + buttons to view associations for NLRC4 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles tissues with high or low expression of NLRC4 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles tissues with high or low expression of NLRC4 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of NLRC4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq tissue samples with high or low expression of NLRC4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles tissues with high or low expression of NLRC4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
BioGPS Human Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of NLRC4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of NLRC4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Gene Expression Profiles cell lines with high or low expression of NLRC4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CellMarker Gene-Cell Type Associations cell types associated with NLRC4 gene from the CellMarker Gene-Cell Type Associations dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of NLRC4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of NLRC4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
ChEA Transcription Factor Targets 2022 transcription factors binding the promoter of NLRC4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
ClinVar Gene-Phenotype Associations phenotypes associated with NLRC4 gene from the curated ClinVar Gene-Phenotype Associations dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing NLRC4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing NLRC4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with NLRC4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with NLRC4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of NLRC4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with NLRC4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
CTD Gene-Chemical Interactions chemicals interacting with NLRC4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
CTD Gene-Disease Associations diseases associated with NLRC4 gene/protein from the curated CTD Gene-Disease Associations dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by NLRC4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with NLRC4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with NLRC4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
DisGeNET Gene-Disease Associations diseases associated with NLRC4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with NLRC4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at NLRC4 gene from the ENCODE Histone Modification Site Profiles dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of NLRC4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of NLRC4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
ESCAPE Omics Signatures of Genes and Proteins for Stem Cells PubMedIDs of publications reporting gene signatures containing NLRC4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
GAD Gene-Disease Associations diseases associated with NLRC4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with NLRC4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing NLRC4 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of NLRC4 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of NLRC4 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of NLRC4 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of NLRC4 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of NLRC4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving NLRC4 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving NLRC4 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving NLRC4 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing NLRC4 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Cellular Component Annotations 2023 cellular components containing NLRC4 protein from the curated GO Cellular Component Annotations 2023 dataset.
GO Cellular Component Annotations 2025 cellular components containing NLRC4 protein from the curated GO Cellular Component Annotations 2025 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by NLRC4 gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by NLRC4 gene from the curated GO Molecular Function Annotations 2023 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by NLRC4 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx eQTL 2025 SNPs regulating expression of NLRC4 gene from the GTEx eQTL 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of NLRC4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of NLRC4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GTEx Tissue Sample Gene Expression Profiles tissue samples with high or low expression of NLRC4 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset.
GTEx Tissue-Specific Aging Signatures tissue samples with high or low expression of NLRC4 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset.
GWASdb SNP-Disease Associations diseases associated with NLRC4 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with NLRC4 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of NLRC4 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HPA Cell Line Gene Expression Profiles cell lines with high or low expression of NLRC4 gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of NLRC4 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of NLRC4 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of NLRC4 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
HPM Cell Type and Tissue Protein Expression Profiles cell types and tissues with high or low expression of NLRC4 protein relative to other cell types and tissues from the HPM Cell Type and Tissue Protein Expression Profiles dataset.
Hub Proteins Protein-Protein Interactions interacting hub proteins for NLRC4 from the curated Hub Proteins Protein-Protein Interactions dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with NLRC4 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for NLRC4 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of NLRC4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
KEA Substrates of Kinases kinases that phosphorylate NLRC4 protein from the curated KEA Substrates of Kinases dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of NLRC4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles cell lines with high or low expression of NLRC4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Expression Profiles dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles cell lines with NLRC4 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of NLRC4 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LOCATE Curated Protein Localization Annotations cellular components containing NLRC4 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain NLRC4 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MGI Mouse Phenotype Associations 2023 phenotypes of transgenic mice caused by NLRC4 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset.
MiRTarBase microRNA Targets microRNAs targeting NLRC4 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of NLRC4 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MPO Gene-Phenotype Associations phenotypes of transgenic mice caused by NLRC4 gene mutations from the MPO Gene-Phenotype Associations dataset.
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations gene perturbations changing expression of NLRC4 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset.
OMIM Gene-Disease Associations phenotypes associated with NLRC4 gene from the curated OMIM Gene-Disease Associations dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for NLRC4 from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of NLRC4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Mouse Gene Perturbations gene perturbations changing expression of NLRC4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PFOCR Pathway Figure Associations 2023 pathways involving NLRC4 protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving NLRC4 protein from the Wikipathways PFOCR 2024 dataset.
Phosphosite Textmining Biological Term Annotations biological terms co-occuring with NLRC4 protein in abstracts of publications describing phosphosites from the Phosphosite Textmining Biological Term Annotations dataset.
PhosphoSitePlus Substrates of Kinases kinases that phosphorylate NLRC4 protein from the curated PhosphoSitePlus Substrates of Kinases dataset.
PID Pathways pathways involving NLRC4 protein from the PID Pathways dataset.
Reactome Pathways 2014 pathways involving NLRC4 protein from the Reactome Pathways dataset.
Reactome Pathways 2024 pathways involving NLRC4 protein from the Reactome Pathways 2024 dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at NLRC4 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of NLRC4 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of NLRC4 gene from the RummaGEO Gene Perturbation Signatures dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of NLRC4 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of NLRC4 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of NLRC4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of NLRC4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores tissues with high expression of NLRC4 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of NLRC4 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with NLRC4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with NLRC4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.
WikiPathways Pathways 2014 pathways involving NLRC4 protein from the Wikipathways Pathways 2014 dataset.
WikiPathways Pathways 2024 pathways involving NLRC4 protein from the WikiPathways Pathways 2024 dataset.