HGNC Family | Homeoboxes, Paired boxes (PAX) |
Name | paired box 4 |
Description | This gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically contain a paired box domain, an octapeptide, and a paired-type homeodomain. These genes play critical roles during fetal development and cancer growth. The paired box 4 gene is involved in pancreatic islet development and mouse studies have demonstrated a role for this gene in differentiation of insulin-producing beta cells. [provided by RefSeq, Jul 2008] |
Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPAX4 is widely recognized as a pivotal transcription factor governing pancreatic islet development by promoting β‐cell lineage commitment, differentiation, proliferation, and survival. Loss‐of‐function mutations (for example, R121W and other missense variants) impair its repressor activity and DNA binding, thereby reducing the formation and functional competency of insulin‐producing β‐cells and predisposing carriers to various forms of diabetes—including maturity‐onset diabetes of the young (MODY), type 2 diabetes, and ketosis‐prone diabetes. Moreover, PAX4 is critical during embryogenesis, where it represses alternate endocrine fates to secure the β‐cell identity, as evidenced by both genetic mutation analyses and promoter studies in human and rodent models."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in determining cell fate, PAX4 expression is finely regulated by external signaling molecules and intrinsic transcriptional networks. Activin A, for instance, enhances PAX4 gene transcription via E‐box–binding factors (E47/E12), and modulation of its promoter by repressor complexes (including those involving neuron‐restrictive silencer elements) further refines its expression. Notably, the PAX4 protein itself exhibits non–cell autonomous functions by virtue of a protein transduction domain that enables its uptake and anti–apoptotic actions in target cells. These regulatory mechanisms and differential activities—exemplified by ethnic and species differences in binding affinities—underscore the complexity of PAX4 regulation in pancreatic and extra–pancreatic contexts."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical role in islet biology, emerging evidence indicates that aberrant PAX4 expression or genetic variation contributes to disease susceptibility and progression in diverse tissues. In the endocrine pancreas, genetic polymorphisms and mutations in PAX4 have been linked not only to various diabetic phenotypes (including gestational diabetes and altered therapeutic responses) but also to differences in β‐cell function and longevity. In parallel, dysregulated PAX4 activity has been implicated in cancer, acting context–dependently as either an oncogene or tumor suppressor—for example, its overexpression in gastric cancer cells enhances migration and invasion via miRNA regulatory networks, while in melanoma its reduced expression appears to inhibit tumor growth. Together with data from recent large–scale genetic and functional studies, these findings underscore the multifaceted role of PAX4 as a key modulator of cell differentiation, survival, and disease risk."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "29"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Y Shimajiri, T Sanke, H Furuta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A missense mutation of Pax4 gene (R121W) is associated with type 2 diabetes in Japanese."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/diabetes.50.12.2864"}], "href": "https://doi.org/10.2337/diabetes.50.12.2864"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11723072"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11723072"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Azuma Kanatsuka, Yoshiharu Tokuyama, Osamu Nozaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Beta-cell dysfunction in late-onset diabetic subjects carrying homozygous mutation in transcription factors NeuroD1 and Pax4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Metabolism (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/meta.2002.34707"}], "href": "https://doi.org/10.1053/meta.2002.34707"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12200761"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12200761"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yoshinori Shimajiri, Michio Shimabukuro, Takeaki Tomoyose, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAX4 mutation (R121W) as a prodiabetic variant in Okinawans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-291x(03)00176-1"}], "href": "https://doi.org/10.1016/s0006-291x(03"}, {"type": "t", "text": "00176-1) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12604352"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12604352"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Daniel M Kemp, Julia C Lin, Joel F Habener "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of Pax4 paired homeodomain gene by neuron-restrictive silencer factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M305891200"}], "href": "https://doi.org/10.1074/jbc.M305891200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12829700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12829700"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Pernilla Holm, Berit Rydlander, Holger Luthman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction and association analysis of a type 1 diabetes susceptibility locus on chromosome 5q11-q13 and the 7q32 chromosomal region in Scandinavian families."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/diabetes.53.6.1584"}], "href": "https://doi.org/10.2337/diabetes.53.6.1584"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15161765"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15161765"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Franck Mauvais-Jarvis, Stuart B Smith, Cédric Le May, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAX4 gene variations predispose to ketosis-prone diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddh341"}], "href": "https://doi.org/10.1093/hmg/ddh341"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15509590"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15509590"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Thierry Brun, Isobel Franklin, Luc St-Onge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The diabetes-linked transcription factor PAX4 promotes {beta}-cell proliferation and survival in rat and human islets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200405148"}], "href": "https://doi.org/10.1083/jcb.200405148"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15596543"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15596543"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Beatriz Sosa-Pineda "}, {"type": "b", "children": [{"type": "t", "text": "The gene Pax4 is an essential regulator of pancreatic beta-cell development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cells (2004)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15650323"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15650323"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "A Biason-Lauber, B Boehm, M Lang-Muritano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of childhood type 1 diabetes mellitus with a variant of PAX4: possible link to beta cell regenerative capacity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetologia (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00125-005-1723-5"}], "href": "https://doi.org/10.1007/s00125-005-1723-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15834548"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15834548"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yoshiharu Tokuyama, Kana Matsui, Toshiharu Ishizuka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Arg121Trp variant in PAX4 gene is associated with beta-cell dysfunction in Japanese subjects with type 2 diabetes mellitus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Metabolism (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.metabol.2005.08.014"}], "href": "https://doi.org/10.1016/j.metabol.2005.08.014"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16423628"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16423628"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Rei Kanno, Takeshi Ogihara, Yasuhiro Igarashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activin A-induced expression of PAX4 in AR42J-B13 cells involves the increase in transactivation of E47/E12."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbaexp.2006.01.004"}], "href": "https://doi.org/10.1016/j.bbaexp.2006.01.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16546275"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16546275"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yinghua Li, Hirokazu Nagai, Toshihito Ohno, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aberrant DNA demethylation in promoter region and aberrant expression of mRNA of PAX4 gene in hematologic malignancies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leuk Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.leukres.2006.04.001"}], "href": "https://doi.org/10.1016/j.leukres.2006.04.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16701883"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16701883"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yun Zhang, Xin-hua Xiao, Heng Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[Association between A1168C polymorphism in PAX4 gene and type 1 diabetes in Han Chinese]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhongguo Yi Xue Ke Xue Yuan Xue Bao (2007)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17633464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17633464"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Jun Lu, Ge Li, Michael S Lan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pax4 paired domain mediates direct protein transduction into mammalian cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2007-0636"}], "href": "https://doi.org/10.1210/en.2007-0636"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17717051"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17717051"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Shinya Hata, Jun-Ichi Hamada, Kazuhiko Maeda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAX4 has the potential to function as a tumor suppressor in human melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2008)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18949370"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18949370"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Ji Wan Park, Yong Ick Ji, Yoon Ho Choi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Candidate gene polymorphisms for diabetes mellitus, cardiovascular disease and cancer are associated with longevity in Koreans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3858/emm.2009.41.11.083"}], "href": "https://doi.org/10.3858/emm.2009.41.11.083"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19641380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19641380"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Min Zhou, Ying Zhang, Dongmei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[PAX4 gene polymorphism and islet autoantibody-negative ketosis-prone diabetes]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhong Nan Da Xue Xue Bao Yi Xue Ban (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3969/j.issn.1672-7347.2010.03.005"}], "href": "https://doi.org/10.3969/j.issn.1672-7347.2010.03.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20360641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20360641"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Wakako Jo, Machiko Endo, Katura Ishizu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel PAX4 mutation in a Japanese patient with maturity-onset diabetes of the young."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tohoku J Exp Med (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1620/tjem.223.113"}], "href": "https://doi.org/10.1620/tjem.223.113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21263211"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21263211"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Suwattanee Kooptiwut, Nattachet Plengvidhya, Titikan Chukijrungroat, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defective PAX4 R192H transcriptional repressor activities associated with maturity onset diabetes of the young and early onset-age of type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Diabetes Complications (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jdiacomp.2012.03.025"}], "href": "https://doi.org/10.1016/j.jdiacomp.2012.03.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22521316"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22521316"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "M Chen, C Hu, R Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of PAX4 genetic variants with oral antidiabetic drugs efficacy in Chinese type 2 diabetes patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacogenomics J (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/tpj.2014.18"}], "href": "https://doi.org/10.1038/tpj.2014.18"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24752311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24752311"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "J Zhang, X Qin, Q Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional control of PAX4-regulated miR-144/451 modulates metastasis by suppressing ADAMs expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2014.259"}], "href": "https://doi.org/10.1038/onc.2014.259"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25151965"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25151965"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Jatuporn Sujjitjoon, Suwattanee Kooptiwut, Nalinee Chongjaroen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAX4 R192H and P321H polymorphisms in type 2 diabetes and their functional defects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jhg.2016.80"}], "href": "https://doi.org/10.1038/jhg.2016.80"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27334367"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27334367"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Chloe Y Y Cheung, Clara S Tang, Aimin Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetologia (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00125-016-4132-z"}], "href": "https://doi.org/10.1007/s00125-016-4132-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27744525"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27744525"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Tianyi Xu, Yiru Shi, Jiangbo Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The rs10229583 polymorphism near paired box gene 4 is associated with gestational diabetes mellitus in Chinese women."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Int Med Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/0300060517714934"}], "href": "https://doi.org/10.1177/0300060517714934"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28730907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28730907"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Soo Heon Kwak, Jeesoo Chae, Seungbok Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nonsynonymous Variants in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "PAX4"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " and "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "GLP1R"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Are Associated With Type 2 Diabetes in an East Asian Population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db18-0361"}], "href": "https://doi.org/10.2337/db18-0361"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29941447"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29941447"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Yan Zhang, Li Ding, Qingfeng Ni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcription factor PAX4 facilitates gastric cancer progression through interacting with miR-27b-3p/Grb2 axis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging (Albany NY) (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/aging.203214"}], "href": "https://doi.org/10.18632/aging.203214"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34162761"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34162761"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Thomas W Laver, Matthew N Wakeling, Olivia Knox, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evaluation of Evidence for Pathogenicity Demonstrates That BLK, KLF11, and PAX4 Should Not Be Included in Diagnostic Testing for MODY."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db21-0844"}], "href": "https://doi.org/10.2337/db21-0844"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35108381"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35108381"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Jenna Ko, Vivian A Fonseca, Hongju Wu "}, {"type": "b", "children": [{"type": "t", "text": "Pax4 in Health and Diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms24098283"}], "href": "https://doi.org/10.3390/ijms24098283"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37175989"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37175989"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Hwee Hui Lau, Nicole A J Krentz, Fernando Abaitua, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-023-41860-z"}], "href": "https://doi.org/10.1038/s41467-023-41860-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37777536"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37777536"}]}]}]}
|
Synonyms | KPD, MODY9 |
Proteins | PAX4_HUMAN |
NCBI Gene ID | 5078 |
API | |
Download Associations | |
Predicted Functions |
![]() |
Co-expressed Genes |
![]() |
Expression in Tissues and Cell Lines |
![]() |
PAX4 has 3,186 functional associations with biological entities spanning 8 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 95 datasets.
Click the + buttons to view associations for PAX4 from the datasets below.
If available, associations are ranked by standardized value
Dataset | Summary | |
---|---|---|
Achilles Cell Line Gene Essentiality Profiles | cell lines with fitness changed by PAX4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset. | |
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of PAX4 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 PAX4 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 PAX4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of PAX4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
BioGPS Cell Line Gene Expression Profiles | cell lines with high or low expression of PAX4 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset. | |
BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of PAX4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
BioGPS Mouse Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of PAX4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset. | |
CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of PAX4 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 PAX4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
CellMarker Gene-Cell Type Associations | cell types associated with PAX4 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 PAX4 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
ChEA Transcription Factor Targets | transcription factors binding the promoter of PAX4 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 PAX4 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 PAX4 gene from the curated ClinVar Gene-Phenotype Associations dataset. | |
CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of PAX4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing PAX4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing PAX4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with PAX4 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 PAX4 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 PAX4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
COSMIC Cell Line Gene Mutation Profiles | cell lines with PAX4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
CTD Gene-Chemical Interactions | chemicals interacting with PAX4 gene/protein from the curated CTD Gene-Chemical Interactions dataset. | |
CTD Gene-Disease Associations | diseases associated with PAX4 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
DepMap CRISPR Gene Dependency | cell lines with fitness changed by PAX4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
DISEASES Curated Gene-Disease Association Evidence Scores | diseases involving PAX4 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset. | |
DISEASES Curated Gene-Disease Association Evidence Scores 2025 | diseases involving PAX4 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset. | |
DISEASES Experimental Gene-Disease Association Evidence Scores | diseases associated with PAX4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset. | |
DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with PAX4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with PAX4 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 PAX4 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 PAX4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
DisGeNET Gene-Phenotype Associations | phenotypes associated with PAX4 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 PAX4 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 PAX4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
ENCODE Transcription Factor Targets | transcription factors binding the promoter of PAX4 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 PAX4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
GAD Gene-Disease Associations | diseases associated with PAX4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
GAD High Level Gene-Disease Associations | diseases associated with PAX4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset. | |
GDSC Cell Line Gene Expression Profiles | cell lines with high or low expression of PAX4 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset. | |
GeneRIF Biological Term Annotations | biological terms co-occuring with PAX4 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 PAX4 from the GeneSigDB Published Gene Signatures dataset. | |
GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of PAX4 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 PAX4 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 PAX4 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 PAX4 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of PAX4 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of PAX4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
GO Biological Process Annotations 2015 | biological processes involving PAX4 gene from the curated GO Biological Process Annotations 2015 dataset. | |
GO Biological Process Annotations 2023 | biological processes involving PAX4 gene from the curated GO Biological Process Annotations 2023 dataset. | |
GO Biological Process Annotations 2025 | biological processes involving PAX4 gene from the curated GO Biological Process Annotations2025 dataset. | |
GO Cellular Component Annotations 2015 | cellular components containing PAX4 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
GO Molecular Function Annotations 2015 | molecular functions performed by PAX4 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
GO Molecular Function Annotations 2023 | molecular functions performed by PAX4 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
GO Molecular Function Annotations 2025 | molecular functions performed by PAX4 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
GTEx Tissue Gene Expression Profiles | tissues with high or low expression of PAX4 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 PAX4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
GWASdb SNP-Disease Associations | diseases associated with PAX4 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset. | |
GWASdb SNP-Phenotype Associations | phenotypes associated with PAX4 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 PAX4 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
HPA Tissue Protein Expression Profiles | tissues with high or low expression of PAX4 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
HPO Gene-Disease Associations | phenotypes associated with PAX4 gene by mapping known disease genes to disease phenotypes from the HPO Gene-Disease Associations dataset. | |
HuGE Navigator Gene-Phenotype Associations | phenotypes associated with PAX4 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
IMPC Knockout Mouse Phenotypes | phenotypes of mice caused by PAX4 gene knockout from the IMPC Knockout Mouse Phenotypes dataset. | |
InterPro Predicted Protein Domain Annotations | protein domains predicted for PAX4 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of PAX4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
KEGG Pathways | pathways involving PAX4 protein from the KEGG Pathways dataset. | |
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of PAX4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of PAX4 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures | small molecule perturbations changing expression of PAX4 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset. | |
LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain PAX4 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by PAX4 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of PAX4 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 PAX4 gene mutations from the MPO Gene-Phenotype Associations dataset. | |
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations | gene perturbations changing expression of PAX4 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset. | |
OMIM Gene-Disease Associations | phenotypes associated with PAX4 gene from the curated OMIM Gene-Disease Associations dataset. | |
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of PAX4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
PFOCR Pathway Figure Associations 2023 | pathways involving PAX4 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
PFOCR Pathway Figure Associations 2024 | pathways involving PAX4 protein from the Wikipathways PFOCR 2024 dataset. | |
Reactome Pathways 2014 | pathways involving PAX4 protein from the Reactome Pathways dataset. | |
Reactome Pathways 2024 | pathways involving PAX4 protein from the Reactome Pathways 2024 dataset. | |
Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles | cell types and tissues with high or low DNA methylation of PAX4 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset. | |
Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at PAX4 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of PAX4 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of PAX4 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of PAX4 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of PAX4 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of PAX4 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 PAX4 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 PAX4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of PAX4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of PAX4 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 PAX4 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 PAX4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
WikiPathways Pathways 2024 | pathways involving PAX4 protein from the WikiPathways Pathways 2024 dataset. | |