# APC

Source: https://onco.cc/targets/apc/  
OnCo record `apc` (Target). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

CIViC 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).

## Fields

- Kind: Target
- Last checked: 2026-09-23
- Also known as: APC regulator of Wnt signaling pathway; Adenomatous polyposis coli protein; DP2; DP3; DP2.5; PPP1R46
- Tags: cancer-genes-wave
- Symbol: APC
- Class: tumor-suppressor
- 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).
- Where found: 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

## 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.

## Sources

- HGNC HGNC:583: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:583
- UniProt P25054: https://www.uniprot.org/uniprotkb/P25054/entry
- NCBI Gene 324: https://www.ncbi.nlm.nih.gov/gene/324
- Ensembl ENSG00000134982: https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000134982

## Connected records

- collections: [CIViC](https://onco.cc/collections/civic/), [IntOGen](https://onco.cc/collections/intogen/), [Open Targets Platform](https://onco.cc/collections/open-targets/)
- cancers: [Anal cancer (squamous cell carcinoma)](https://onco.cc/cancers/anal/), [Biliary tract cancer (all types)](https://onco.cc/cancers/biliary-tract-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Neuroendocrine tumours](https://onco.cc/cancers/neuroendocrine/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- drugs: [Nirogacestat](https://onco.cc/drugs/nirogacestat/)
- pathways: [Colorectal cancer (KEGG map)](https://onco.cc/pathways/colorectal-cancer-signalling/), [Gastric cancer (KEGG map)](https://onco.cc/pathways/gastric-cancer-signalling/), [Mitosis & the spindle assembly checkpoint](https://onco.cc/pathways/mitotic-spindle-checkpoint/), [Wnt / β-catenin](https://onco.cc/pathways/wnt/)
- terms: [Colibactin](https://onco.cc/terms/colibactin/), [Driver mutation](https://onco.cc/terms/driver-mutation/)
- key papers: [A genetic model for colorectal tumorigenesis](https://onco.cc/key-papers/paper-fearon-cell/), [Clinical sequencing defines the genomic landscape of metastatic colorectal cancer](https://onco.cc/key-papers/paper-yaeger-metastatic-colorectal-genomic-landscape-cancer-cell-2018/), [Comprehensive molecular characterization of human colon and rectal cancer](https://onco.cc/key-papers/paper-tcga-colorectal-comprehensive-characterization-nature-2012/), [Genetic alterations during colorectal-tumor development](https://onco.cc/key-papers/paper-vogelstein-genetic-alterations-colorectal-tumor-development-nejm-1988/), [Genetic mechanisms of immune evasion in colorectal cancer](https://onco.cc/key-papers/paper-grasso-immune-evasion-colorectal-cancer-discov-2018/), [Geographic and age variations in mutational processes in colorectal cancer](https://onco.cc/key-papers/paper-diaz-gay-colibactin-geographic-age-mutational-processes-nature-2025/), [Integrated genomic analysis reveals mutated ELF3 as a potential gallbladder cancer vaccine candidate](https://onco.cc/key-papers/paper-pandey-gallbladder-elf3-nat-commun-2020/), [Oncogenic genomic alterations, clinical phenotypes and outcomes in metastatic castration-sensitive prostate cancer](https://onco.cc/key-papers/paper-stopsack-mcspc-genomic-alterations-outcomes-ccr-2020/), [Recurrent R-spondin fusions in colon cancer](https://onco.cc/key-papers/paper-seshagiri-rspo-fusions-colon-nature-2012/), [SU2C-PCF: integrative clinical genomics of advanced prostate cancer](https://onco.cc/key-papers/paper-robinson-integrative-clinical-genomics-advanced-prostate-cell-2015/), [TGF-beta drives immune evasion in genetically reconstituted colon cancer metastasis](https://onco.cc/key-papers/paper-tauriello-tgfbeta-immune-evasion-colorectal-nature-2018/), [The landscape of somatic mutation in normal colorectal epithelial cells](https://onco.cc/key-papers/paper-lee-six-somatic-mutation-normal-colorectal-crypts-nature-2019/)
- roadmaps: [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](https://onco.cc/roadmaps/colorectal-roadmap/)
- ideas: [Find out what is driving early-onset bowel cancer, starting with colibactin, before extending screening any further](https://onco.cc/ideas/idea-crc-early-onset-cause-hunt/)

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JSON: https://onco.cc/api/v1/entities/apc.json