APC

APC regulator of Wnt signaling pathway

11 disorders 5 untyped 3 no genetic record 2 causative 1 risk factor 5q22.2 gene with protein product

HGNC:583 Monarch NCBI Gene 324 ENSG00000134982 UniProt P25054 OMIM 611731

Aliases: DP2, DP3, DP2.5, PPP1R46.

Normal function · from ai-gene-review (P25054, commit 79fe13b38970) · AI-generated, not KB evidence

APC is a large, multidomain tumor suppressor that coordinates beta-catenin turnover and cytoskeletal organization. Its central repeats bind beta-catenin and its SAMP motifs engage AXIN in the cytoplasmic destruction complex, helping recruit and present beta-catenin to kinases and ubiquitination machinery. Its C-terminal regions bind microtubules, associate with microtubule-end proteins and directly recruit actin monomers to nucleate filaments. These activities contribute to cell polarity, migration and accurate mitosis. APC also binds regulatory partners, including Asef-family nucleotide-exchange factors, whose autoinhibition it can relieve. APC occupies cytoplasmic, cortical, junctional and nuclear pools; truncating variants disrupt several of these separable functions and underlie familial adenomatous polyposis and many sporadic colorectal cancers.

Binds beta-catenin and organizes its recruitment and processing in the cytoplasmic destruction complex, supporting phosphorylation, ubiquitination and proteasomal turnover by the associated enzymes.

molecular function: beta-catenin binding · directly involved in: negative regulation of canonical Wnt signaling pathway; proteasome-mediated ubiquitin-dependent protein catabolic process · locations: cytosol · in complex: beta-catenin destruction complex

Binds and stabilizes microtubules and associates with microtubule-end partners, helping organize cortical and kinetochore microtubules during migration and mitosis.

molecular function: microtubule binding · directly involved in: negative regulation of microtubule depolymerization; regulation of attachment of spindle microtubules to kinetochore; cell migration · locations: cytoplasmic microtubule; kinetochore

Binds actin and recruits actin monomers to assemble a filament-nucleation seed. APC remains at the nucleation site while its formin partner can drive barbed-end elongation; this activity is separable from APC microtubule binding.

molecular function: actin binding · directly involved in: actin nucleation · locations: cytoplasm

Binds Asef-family exchange factors through its armadillo region and relieves their autoinhibition. Asef performs nucleotide exchange; APC supplies the activating interaction. The source-specific substrate preferences are not generalized to a single downstream GTPase.

molecular function: guanyl nucleotide exchange factor activator activity · locations: cytoplasm; plasma membrane

In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

Disorder	Relationship	Where the gene appears
Desmoid Tumor	causative germline	mechanism: Constitutive Activation of the Wnt-beta-catenin Axis; Germline APC Loss of Function
Familial Nonmedullary Thyroid Carcinoma	causative germline
Small Intestine Cancer	risk factor	mechanism: Adenoma-Carcinoma Sequence and Wnt-APC Activation subtype: Adenocarcinoma
Classic Familial Adenomatous Polyposis	untyped Germline pathogenic loss-of-function variants	mechanism: APC promoter 1B-dependent allelic silencing; Germline APC loss-of-function predisposition; Somatic APC Second-Hit Inactivation (Knudson Two-Hit)
Colon Adenocarcinoma	untyped Somatic loss of function
Familial Adenomatous Polyposis	untyped Germline Loss-of-Function Mutations
Hepatoblastoma	untyped Germline Predisposition
Medulloblastoma, WNT-Activated	untyped Germline/Somatic Mutation
MBD4-Related Tumor Predisposition Syndrome	no genetic record somatic loss of function	mechanism: Somatic APC Inactivation by CpG>TpG Transition
MUTYH-Associated Polyposis	no genetic record somatic loss of function	mechanism: Somatic APC Inactivation by Transversion
Thymic Neuroendocrine Carcinoma	no genetic record	mechanism: Chromatin Regulator Loss

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

ClinGen disease	MOI	Classification	dismech entry
gastric adenocarcinoma and proximal polyposis of the stomach MONDO:0017790	AD	Definitive 2022-06-20	no dismech entry
classic or attenuated familial adenomatous polyposis MONDO:0021057	AD	Definitive 2022-06-20	no dismech entry

Mechanism modules · computed from kb/

germline_two_hit_tumor_predisposition via Classic Familial Adenomatous Polyposis

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.