PUBLISHED: 2nd December 2025
The CTNNA1 gene encodes a protein called alpha-E-catenin. Alpha-E-catenin helps hold cells together to form healthy tissues.
What is a CTNNA1 mutation?
People with a mutation in the CTNNA1 gene may develop hereditary diffuse stomach (gastric) cancer or HDGC. They may also develop a condition affecting the eyes called butterfly-shaped pigmentary macular dystrophy, (see Other Considerations below).
What is hereditary diffuse gastric cancer?
HDGC is a rare type of stomach cancer. Only about 1% to 3% of stomach cancers are HDGC. HDGC can be caused by an inherited mutation in CTNNA1 or a related gene known as CDH1.
HDGC is very difficult to identify in its early stages due to its unique growth pattern. Unlike other types of gastric cancer that form a solid, visible tumor, HDGC cells spread through the stomach wall, often while the lining continues to appear normal. Abnormal cells grow one by one or in small clusters that are not visible with an endoscope. For this reason, most cases of HDGC are diagnosed in later stages.
What are the risks of cancer for people with a CTNNA1 mutation?
The lifetime risk of stomach cancer for people with a CTNNA1 mutation is not well known. However, some studies suggest that it may be as high as 57%. However, this estimate is based on a study of families with a large number of HDGC cases.
| Cancer type | Lifetime risk with a CTNNA1 mutation | Lifetime risk for the general population |
| Stomach | 49-57% | Less than 1% |
The related gene, CDH1, increases the risk for both gastric cancer and a type of breast cancer known as lobular carcinoma. Currently, it is not known if there is also an increased risk for breast cancer in women with CTNNA1 mutations.
What can people with a CTNNA1 mutation do?
As with many rare cancer predisposition genes and syndromes, there is limited research to support cancer screening or treatment recommendations specifically for CTNNA1 mutation carriers.
The National Comprehensive Cancer Network (NCCN) is a US-based panel of experts who develop guidelines for cancer risk management and treatment. NCCN currently has established guidelines for CDH1 but not for CTNNA1. Their current guidelines state that they plan to include specific advice for people with CTNNA1 mutations in future versions of their stomach cancer risk management guidelines.
People with an inherited mutation in CTNNA1 may also qualify for specific treatments or clinical trials.
Cancer risk management for people with a CTNNA1 mutation
Currently, the International Gastric Cancer Linkage Consortium (IGCLC) recommends that people with an inherited mutation in CTNNA1 undergo yearly endoscopic surveillance by a center with expertise in managing people at risk for HDGC. The Consortium also recommends that people with CTNNA1 mutations consider risk-reducing total gastrectomy (removal of the stomach) depending on the results of biopsies during endoscopic screening and family history of HDGC. The Consortium guidelines are summarized below.
| Cancer type | Beginning age | Recommendation |
| Stomach | Individualized | Upper endoscopy (a procedure that lets your doctor see inside your stomach and small intestine) with targeted and random biopsies every year. |
| Individualized | Consider removal of the stomach (gastrectomy) based on screening and biopsy results. | |
| Consider testing and treating H. pylori infection, if present. |
For people with a CTNNA1 mutation, when to begin personalized screening could depend on your family's cancer history and the ages at which relatives were diagnosed.
If you have an inherited mutation in CTNNA1, we recommend that you speak with a genetics expert who can look at your personal and family history of cancer and help you decide on a plan for managing your risk.
Cancer treatment
There are no specific treatment considerations for people with CTNNA1 mutations.
If you have a CTNNA1 mutation, try to find a team of doctors with experience in genetics and rare hereditary cancer syndromes.
Other considerations
Some CTNNA1 mutations have been associated with a rare eye disorder known as butterfly-shaped pigment dystrophy. This is an abnormal accumulation of a yellow-brown pigment in the eye that appears as a distinctive butterfly shape, leading to a slow loss of vision. Pattern dystrophies are frequently found during routine eye exams.
Ask your doctor
If you or a family member has a mutation in CTNNA1, consider asking your doctor the following:
- What symptoms should I watch for?
- Are there clinical trials or new options for cancer prevention or treatment I should know about?
As we learn more about CTNNA1 mutations, we may discover more about the risk of other types of cancer. Check with a genetics expert to ensure that you receive the most up-to-date information about cancer risks and treatments for people with a CTNNA1 mutation.