{"entity":{"id":"zfhx3","kind":"target","name":"ZFHX3","aka":["zinc finger homeobox 3","Zinc finger homeobox protein 3","ZNF927","FLJ26184","ATBF1","C16orf47"],"tldr":"ZFHX3 (Zinc finger homeobox protein 3) is a protein that switches other genes on and off. The public catalogues list it as an oncogene driver and a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Prostate cancer, Endometrial cancer, Breast cancer and 5 more.","summary":"Transcriptional regulator which can act as an activator or a repressor. Inhibits the enhancer element of the AFP gene by binding to its AT-rich core sequence. In concert with SMAD-dependent TGF-beta signalling can repress the transcription of AFP via its interaction with SMAD2/3.\n\nOpen Targets scores its association with cancer at 0.81 (direct and indirect evidence; datatypes literature 0.96, genetic association 0.67, somatic mutation 0.92). IntOGen calls it a driver in 17 cohorts (4 activating, 13 loss-of-function), covering Bladder Urothelial Carcinoma, Invasive Breast Carcinoma, Diffuse Large B-Cell Lymphoma, NOS, Hepatocellular Carcinoma, Osteosarcoma, Plasma Cell Myeloma and others.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:777","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:777"},{"label":"UniProt Q15911","url":"https://www.uniprot.org/uniprotkb/Q15911/entry"},{"label":"NCBI Gene 463","url":"https://www.ncbi.nlm.nih.gov/gene/463"},{"label":"Ensembl ENSG00000140836","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000140836"}],"tags":["cancer-genes-wave"],"related":["open-targets","intogen"],"cancers":["prostate","endometrial","breast-cancer","thyroid","hcc","urothelial","multiple-myeloma","vulvar"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it an activating (Act) driver in 4 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 13 cohorts. Evidence tier \"cohort-driver\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"ZFHX3","role":["oncogene-driver","tumour-suppressor"],"evidenceTier":"cohort-driver","sources":[{"label":"HGNC HGNC:777","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:777","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt Q15911","url":"https://www.uniprot.org/uniprotkb/Q15911/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000140836","url":"https://platform.opentargets.org/target/ENSG00000140836/associations","note":"association with cancer (MONDO_0004992) 0.81; per-cancer scores at or above 0.5: colorectal cancer 0.53, gastric cancer 0.51, prostate cancer 0.67, endometrial cancer 0.59, melanoma 0.52, thyroid cancer 0.50 (GraphQL API, CC0)"},{"label":"IntOGen ZFHX3","url":"https://www.intogen.org/search?gene=ZFHX3","note":"driver in 17 cohorts (Act 4, LoF 13); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"hgnc":"HGNC:777","ensembl":"ENSG00000140836","uniprot":"Q15911","entrez":"463","biology":"Transcriptional regulator which can act as an activator or a repressor. Inhibits the enhancer element of the AFP gene by binding to its AT-rich core sequence. In concert with SMAD-dependent TGF-beta signalling can repress the transcription of AFP via its interaction with SMAD2/3. Regulates the circadian locomotor rhythms via transcriptional activation of neuropeptidergic genes which are essential for intercellular synchrony and rhythm amplitude in the suprachiasmatic nucleus (SCN) of the brain. Regulator of myoblasts differentiation through the binding to the AT-rich sequence of MYF6 promoter and promoter repression. Down-regulates the MUC5AC promoter in gastric cancer. Location: Nucleus; Cytoplasm (UniProt). Locus 16q22.2-q22.3 (HGNC).","whereFound":["Prostate cancer: Open Targets association 0.67 with prostate cancer (MONDO_0008315); IntOGen driver in 3 cohorts (PRAD)","Endometrial cancer: Open Targets association 0.59 with endometrial cancer (MONDO_0011962); IntOGen driver in 3 cohorts (UCEC)","Breast cancer: Open Targets association 0.61 with breast cancer (MONDO_0007254); IntOGen driver in 2 cohorts (BRCA)","Thyroid cancer: Open Targets association 0.50 with thyroid cancer (MONDO_0002108); IntOGen driver in 2 cohorts (WDTC)","Hepatocellular carcinoma: IntOGen driver in 2 cohorts (HCC)","Bladder & urothelial cancer: IntOGen driver in 1 cohort (BLCA)"],"targetClass":"transcription","prevalence":[]},"route":"/targets/zfhx3/","neighbours":{"collection":[{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"urothelial","kind":"cancer","name":"Bladder & urothelial cancer","route":"/cancers/urothelial/"},{"id":"breast-cancer","kind":"cancer","name":"Breast cancer (all types)","route":"/cancers/breast-cancer/"},{"id":"endometrial","kind":"cancer","name":"Endometrial cancer","route":"/cancers/endometrial/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"},{"id":"vulvar","kind":"cancer","name":"Vulvar cancer","route":"/cancers/vulvar/"}]}}