APC is a tumor suppressor gene whose protein acts as a key brake on the Wnt signaling pathway by helping mark the growth-promoting protein beta-catenin for destruction; it also participates in cell migration, adhesion, and apoptosis. Inherited mutations in APC cause familial adenomatous polyposis (FAP), an autosomal dominant condition characterized by numerous colorectal polyps and a very high risk of colorectal cancer, with related forms including attenuated FAP and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). Somatic APC mutations are found in roughly 50-80% of sporadic colorectal cancers, where they act as early tumor-initiating events, and are also observed in some breast, stomach, and prostate cancers. Loss of APC function leaves Wnt signaling abnormally active, driving uncontrolled cell growth, which makes APC a central tumor suppressor in colorectal cancer.
This APC variant affects a tumor-suppressor gene whose loss of Wnt pathway control underlies inherited familial adenomatous polyposis and contributes to colorectal tumor initiation.
BS1 strong: gnomAD v4.1 grpmax FAF 0.0001909 exceeds the APC threshold of 0.00001. BP1 supporting: p.Ala1358Thr is an APC missense change at codon 1358, outside the excluded codons 1021-1035.
European (non-Finnish) 251 / 1,180,032 |
0.021% |
African/African American 3 / 74,900 |
0.004% |
Admixed American 1 / 59,976 |
0.0017% |
Remaining individuals 1 / 62,488 |
0.0016% |
European (non-Finnish) 20 / 128,560 |
0.016% |
Remaining individuals 1 / 7,198 |
0.014% |
Admixed American 1 / 35,412 |
0.0028% |
