{"entity":{"id":"apc","kind":"target","name":"APC","aka":["APC regulator of Wnt signaling pathway","Adenomatous polyposis coli protein","DP2","DP3","DP2.5","PPP1R46"],"tldr":"APC (Adenomatous polyposis coli protein) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a drug target, an oncogene driver, a tumour suppressor and a biomarker, and an approved or late-stage drug is recorded against it. Tied to Colorectal cancer, Gastric & gastro-oesophageal junction cancer, Hepatocellular carcinoma and 5 more.","summary":"Tumour suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signalling as a negative regulator. APC activity is correlated with its phosphorylation state.\n\nCIViC holds 5 clinical evidence items and 0 assertions across 2 variants, naming JW55, G007-LK, Nirogacestat and Regorafenib. Open Targets scores its association with cancer at 0.91 (direct and indirect evidence; datatypes genetic literature 0.79, affected pathway 0.86, literature 1.00, genetic association 0.90, somatic mutation 0.97, animal model 0.88). IntOGen calls it a driver in 43 cohorts (2 activating, 41 loss-of-function), covering Acute Myeloid Leukaemia, Anal Squamous Cell Carcinoma, Cholangiocarcinoma, Colon Adenocarcinoma, Colorectal Adenocarcinoma, Cutaneous Squamous Cell Carcinoma and others. In OnCo, 1 product record names it (Nirogacestat).","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:583","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:583"},{"label":"UniProt P25054","url":"https://www.uniprot.org/uniprotkb/P25054/entry"},{"label":"NCBI Gene 324","url":"https://www.ncbi.nlm.nih.gov/gene/324"},{"label":"Ensembl ENSG00000134982","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000134982"}],"tags":["cancer-genes-wave"],"related":["civic","open-targets","intogen"],"cancers":["colorectal","gastric","hcc","prostate","esophageal","biliary-tract-cancer","anal","neuroendocrine"],"sections":[],"technologies":[],"targets":[],"drugs":["nirogacestat"],"companies":[],"institutions":[],"pathways":["colorectal-cancer-signalling","gastric-cancer-signalling","mitotic-spindle-checkpoint","wnt"],"terms":["driver-mutation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-tcga-colorectal-comprehensive-characterization-nature-2012","paper-yaeger-metastatic-colorectal-genomic-landscape-cancer-cell-2018","paper-seshagiri-rspo-fusions-colon-nature-2012","paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020"],"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: CIViC lists 4 therapies; IntOGen calls it an activating (Act) driver in 2 cohorts; IntOGen calls it a loss-of-function (LoF) driver in 41 cohorts; CIViC holds 5 clinical evidence items on its variants. Evidence tier \"approved-drug\" is the strongest of those signals.","Prevalence not recorded: none of the sources gives a positivity rate.","Colorectal cancer: mutated in 58 to 77% by cohort, with deep deletion and intronic splice disruption on top (cBioPortal). It is the gatekeeper of the conventional adenoma-carcinoma sequence, the first hit in the 1988 staging series (Vogelstein 1988), and the WNT pathway it guards is altered in 93% of tumours in the TCGA analysis and 96% once intronic APC splice events and large in-frame CTNNB1 deletions are counted (Yaeger 2018). Where APC is intact the pathway is usually broken by RNF43, AXIN2, CTNNB1 or an RSPO fusion instead (Seshagiri 2012). APC is less often mutated on the right (65.0% against 77.6%) and in mismatch repair deficient tumours."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"APC","role":["drug-target","oncogene-driver","tumour-suppressor","biomarker"],"evidenceTier":"approved-drug","sources":[{"label":"HGNC HGNC:583","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:583","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P25054","url":"https://www.uniprot.org/uniprotkb/P25054/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"CIViC gene APC","url":"https://civicdb.org/features/66","note":"5 evidence items, 0 assertions, 2 variants; diseases: Colorectal Cancer, Colon Carcinoma, Desmoid Tumour (GraphQL API, CC0)"},{"label":"Open Targets ENSG00000134982","url":"https://platform.opentargets.org/target/ENSG00000134982/associations","note":"association with cancer (MONDO_0004992) 0.91; per-cancer scores at or above 0.5: non-small cell lung carcinoma 0.56, colorectal cancer 0.86, gastric cancer 0.81, oesophageal cancer 0.55, hepatocellular carcinoma 0.74, prostate cancer 0.65 (GraphQL API, CC0)"},{"label":"IntOGen APC","url":"https://www.intogen.org/search?gene=APC","note":"driver in 43 cohorts (Act 2, LoF 41); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificity":"tumour-specific","distribution":"many-types","specificityNote":"Tumour-specific alteration: 1 of 1 medicines aimed at it name a mutant, fusion, exon or hotspot in their mechanism (Nirogacestat), an alteration absent from normal cells. HPA APC: RNA tissue enhanced (brain 39 nTPM); high antibody staining in 14 normal tissues; highest cancer staining prostate cancer (6 of 11 high). Distribution: 8 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Colorectal cancer, Gastric & gastro-oesophageal junction cancer, Hepatocellular carcinoma, Prostate cancer, Oesophageal cancer, Biliary tract cancer (all types), Anal cancer (squamous cell carcinoma) and more); Open Targets associates it with 22 specific cancer types at or above 0.5 (familial adenomatous polyposis 1, classic familial adenomatous polyposis, colorectal cancer, gastric adenocarcinoma and proximal polyposis of the stomach, colon carcinoma, colorectal adenocarcinoma and more). (Rule 4 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Nirogacestat"},{"label":"Human Protein Atlas APC tissue","url":"https://www.proteinatlas.org/ENSG00000134982-APC/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000134982 associations","url":"https://platform.opentargets.org/target/ENSG00000134982/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:583","ensembl":"ENSG00000134982","uniprot":"P25054","entrez":"324","firstDescribed":1991,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Joslyn et al, Cell, 1991, \"Identification of deletion mutations and three new genes at the familial polyposis locus\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/1678319/","biology":"Tumour suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signalling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signalling pathway in colorectal tumour cells. Location: Cell junction, adherens junction; Cytoplasm, cytoskeleton; Cell projection, lamellipodium; Cell projection, ruffle membrane (UniProt). Locus 5q22.2 (HGNC).","whereFound":["Colorectal cancer: Open Targets association 0.86 with colorectal cancer (MONDO_0005575); CIViC evidence names this disease","Gastric & gastro-oesophageal junction cancer: Open Targets association 0.81 with gastric cancer (MONDO_0001056); IntOGen driver in 6 cohorts (EGC, STAD, STOMACH)","Hepatocellular carcinoma: Open Targets association 0.74 with hepatocellular carcinoma (MONDO_0007256); IntOGen driver in 2 cohorts (HCC)","Prostate cancer: Open Targets association 0.65 with prostate cancer (MONDO_0008315); IntOGen driver in 7 cohorts (PRAD, PROSTATE)","Oesophageal cancer: Open Targets association 0.55 with oesophageal cancer (MONDO_0007576); IntOGen driver in 4 cohorts (ESCA, ESCC)","Biliary tract cancer: Open Targets association 0.58 with biliary tract cancer (MONDO_0003060)","Colorectal cancer: inactivating mutation (wnt pathway gatekeeper) 58-77%","Prostate cancer: activating ctnnb1 exon 3 mutation, or apc inactivation 2-10% depending on disease state"],"targetClass":"tumor-suppressor","prevalence":[{"cancerId":"colorectal","pct":"58-77","measure":"Inactivating mutation (WNT pathway gatekeeper)","source":"https://www.cbioportal.org/study/summary?id=crc_msk_2026","note":"cBioPortal: 5,400 of 7,237, 74.6%, in crc_msk_2026; 867 of 1,134, 76.5%, in crc_msk_2017; 1,145 of 1,516, 75.5%, in crc_eo_2020; 387 of 534, 72.5%, in coadread_tcga_pan_can_atlas_2018; 168 of 224, 75.0%, in coadread_tcga_pub; 361 of 619, 58.3%, in coadread_dfci_2016; 451 of 1,015, 44.4%, in crc_sysucc_2022. Deep deletion adds 40 of 7,237 (crc_msk_2026) and 18 of 592 (TCGA), and structural variants disrupt APC in a further 54 of 7,237 samples. The TCGA analysis found WNT signalling altered in 93% of tumours (Cancer Genome Atlas Network 2012); adding intronic APC splice alterations and large in-frame CTNNB1 deletions took oncogenic WNT alterations to 96% of 1,134 prospectively sequenced cancers (Yaeger 2018)."},{"cancerId":"prostate","pct":"2-10","measure":"Activating CTNNB1 exon 3 mutation, or APC inactivation","source":"https://www.cbioportal.org/study/summary?id=prostate_msk_2024","note":"cBioPortal mutation: CTNNB1 89 of 2,260, 3.9%, in prostate_msk_2024; 23 of 424, 5.4%, in prad_mcspc_mskcc_2020; 19 of 444, 4.3%, in prad_su2c_2019; 11 of 494, 2.2%, in prad_tcga_pan_can_atlas_2018. APC mutation 176 of 2,260, 7.8%, in prostate_msk_2024; 36 of 424, 8.5%, in prad_mcspc_mskcc_2020; 31 of 444, 7.0%, in prad_su2c_2019, with deep deletion adding 1 to 10%. The CTNNB1 records cluster on the degron: in prostate_msk_2024, S37F 9, T41A 9, D32Y 7, T41I 7, S45P 6 of 94 records."}]},"route":"/targets/apc/","neighbours":{"collection":[{"id":"civic","kind":"collection","name":"CIViC","route":"/collections/civic/"},{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"anal","kind":"cancer","name":"Anal cancer (squamous cell carcinoma)","route":"/cancers/anal/"},{"id":"biliary-tract-cancer","kind":"cancer","name":"Biliary tract cancer (all types)","route":"/cancers/biliary-tract-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"neuroendocrine","kind":"cancer","name":"Neuroendocrine tumours","route":"/cancers/neuroendocrine/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"drug":[{"id":"nirogacestat","kind":"drug","name":"Nirogacestat","route":"/drugs/nirogacestat/"}],"pathway":[{"id":"colorectal-cancer-signalling","kind":"pathway","name":"Colorectal cancer (KEGG map)","route":"/pathways/colorectal-cancer-signalling/"},{"id":"gastric-cancer-signalling","kind":"pathway","name":"Gastric cancer (KEGG map)","route":"/pathways/gastric-cancer-signalling/"},{"id":"mitotic-spindle-checkpoint","kind":"pathway","name":"Mitosis & the spindle assembly checkpoint","route":"/pathways/mitotic-spindle-checkpoint/"},{"id":"wnt","kind":"pathway","name":"Wnt / β-catenin","route":"/pathways/wnt/"}],"term":[{"id":"colibactin","kind":"term","name":"Colibactin","route":"/terms/colibactin/"},{"id":"driver-mutation","kind":"term","name":"Driver mutation","route":"/terms/driver-mutation/"}],"paper":[{"id":"paper-fearon-cell","kind":"paper","name":"A genetic model for colorectal tumorigenesis","route":"/key-papers/paper-fearon-cell/"},{"id":"paper-yaeger-metastatic-colorectal-genomic-landscape-cancer-cell-2018","kind":"paper","name":"Clinical sequencing defines the genomic landscape of metastatic colorectal cancer","route":"/key-papers/paper-yaeger-metastatic-colorectal-genomic-landscape-cancer-cell-2018/"},{"id":"paper-tcga-colorectal-comprehensive-characterization-nature-2012","kind":"paper","name":"Comprehensive molecular characterization of human colon and rectal cancer","route":"/key-papers/paper-tcga-colorectal-comprehensive-characterization-nature-2012/"},{"id":"paper-vogelstein-genetic-alterations-colorectal-tumor-development-nejm-1988","kind":"paper","name":"Genetic alterations during colorectal-tumor development","route":"/key-papers/paper-vogelstein-genetic-alterations-colorectal-tumor-development-nejm-1988/"},{"id":"paper-grasso-immune-evasion-colorectal-cancer-discov-2018","kind":"paper","name":"Genetic mechanisms of immune evasion in colorectal cancer","route":"/key-papers/paper-grasso-immune-evasion-colorectal-cancer-discov-2018/"},{"id":"paper-diaz-gay-colibactin-geographic-age-mutational-processes-nature-2025","kind":"paper","name":"Geographic and age variations in mutational processes in colorectal cancer","route":"/key-papers/paper-diaz-gay-colibactin-geographic-age-mutational-processes-nature-2025/"},{"id":"paper-pandey-gallbladder-elf3-nat-commun-2020","kind":"paper","name":"Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate","route":"/key-papers/paper-pandey-gallbladder-elf3-nat-commun-2020/"},{"id":"paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020","kind":"paper","name":"Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer","route":"/key-papers/paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020/"},{"id":"paper-seshagiri-rspo-fusions-colon-nature-2012","kind":"paper","name":"Recurrent R-spondin fusions in colon cancer","route":"/key-papers/paper-seshagiri-rspo-fusions-colon-nature-2012/"},{"id":"paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015","kind":"paper","name":"SU2C-PCF: integrative clinical genomics of advanced prostate cancer","route":"/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/"},{"id":"paper-tauriello-tgfbeta-immune-evasion-colorectal-nature-2018","kind":"paper","name":"TGF-beta drives immune evasion in genetically reconstituted colon cancer metastasis","route":"/key-papers/paper-tauriello-tgfbeta-immune-evasion-colorectal-nature-2018/"},{"id":"paper-lee-six-somatic-mutation-normal-colorectal-crypts-nature-2019","kind":"paper","name":"The landscape of somatic mutation in normal colorectal epithelial cells","route":"/key-papers/paper-lee-six-somatic-mutation-normal-colorectal-crypts-nature-2019/"}],"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"}],"idea":[{"id":"idea-crc-early-onset-cause-hunt","kind":"idea","name":"Find out what is driving early-onset bowel cancer, starting with colibactin, before extending screening any further","route":"/ideas/idea-crc-early-onset-cause-hunt/"}]}}