PUBLISHED: 20th October 2026
The SMARCA4 gene is a tumor suppressor. The gene makes a protein called BRG1. BRG1prevents cells from growing and dividing too rapidly or uncontrollably. BRG1 helps open DNA so the cell can read it, fix damage, and make copies when needed.
What is a SMARC4 mutation?
People with an inherited mutation in SMARCA4 have rhabdoid tumor predisposition syndrome 2 (RTPS2). Children with RTPS2 have a high risk of developing cancerous growths called rhabdoid tumors. These tumors most often occur in the brain and spinal cord or in the kidney, but they can occur in other organs and tissues of the body.
Rhabdoid tumors can develop at any time from birth through adulthood, but they are most common in babies and very young children. The highest risk is in early childhood, usually before age 1 or under age 3. The risk of developing rhabdoid tumors drops as a person gets older.
Women with an inherited SMARCA4 mutation face a high risk of developing small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). SCCOHT is a rare and aggressive ovarian cancer that usually occurs in the mid-20s, although one-third of cases occur in teenagers or young women under 20.
SCCOHT accounts for less than 0.01% of all ovarian cancers and fewer than 500 total cases have been reported in medical literature.
What are the risks of cancer for people with a SMARCA4 mutation?
The lifetime risk of rhabdoid tumors or SCCOHT in people with a SMARCA4 mutation is not well known. There is evidence that an inherited mutation in SMARCA4 may increase the risk of breast cancer and a rare type of uterine cancer but there is not enough data to determine risk.
| Cancer type | Lifetime risk with a SMARCA4 mutation | Lifetime risk for the general population |
| Breast | unknown | 12.5% |
| Ovarian (SCCOHT) | High; exact risk is unknown | 1.1% |
| Rhabdoid tumors | Increased risk; exact risk is unknown | 0.000065% |
| Undifferentiated uterine cancer | unknown | 0.001% |
What can people with a SMARCA4 mutation do?
As with many rare cancer predisposition genes and syndromes, there is limited research to support cancer screening or treatment recommendations specifically for SMARCA4 mutation carriers. For people with a SMARCA4 mutation, when to begin personalized screening could depend on your family's cancer history and the ages at which relatives were diagnosed.
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 guidelines for risk management of ovarian cancer (SCCOHT) for people with a SMARCA4 mutation.
Risk management guidelines for rhabdoid tumors from the American Association of Cancer Research (AACR) and experts who study RTPS2 are summarized below.
There are no specific medical management guidelines for breast or undifferentiated uterine cancers.
| Cancer | Recommendation | Beginning age | Frequency | Note | Source |
| SCCOHT (ovarian cancer) | Abdominal and pelvic ultrasound every six months | After age 5 | Every six months | *Nemes K, et al. | |
| SCCOHT (ovarian cancer) | Consider RRSO at a young age based on family history and planning | N/A | N/A | RRSO with delayed oophorectomy is not recommended since the cell type of origin for SCCOHT is unknown | NCCN and *Nemes K, et al. |
| Rhabdoid tumors | Whole body MRI | At the time of diagnosis of RTPS | Yearly after age 5 | *Nemes K, et al. and **AACR | |
| Rhabdoid tumors | Brain and spine MRI | At the time of birth | Every 4 to 6 weeks until age 6 months (or at least every 2-3 months)*, Every 4 to 6 weeks until age 6 months (not least every 2-3 months)**, every 2 to 3 months until age 5* and**, every 2 to 3 years until at least age 10* and **. | *Nemes K, et al. and **AACR |
*Nemes K, Bens S, Bourdeaut F, et al. Rhabdoid Tumor Predisposition Syndrome. 2017 Dec 7 [updated 2022 May 12]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993–2026.
**Greer MC, States LJ, Malkin D, et al. Update on Whole-Body MRI Surveillance for Pediatric Cancer Predisposition Syndromes. Clin Cancer Res. 2024 Nov 15;30(22):5021-5033. Erratum in: Clin Cancer Res. 2025 Oct 15;31(20):4383.
If you have an inherited mutation in SMARCA4, 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
Because of the rarity of RTPS2, treatment standards are evolving. Most individuals are treated using multiple intensive therapies, including surgery, radiation, and chemotherapy. The intensive treatments in children with RTPS2 lead to a high rate of secondary complications.
At present, there is no standard treatment for SCCOHT. However, a combination of surgery and chemotherapy is most frequently used.
People with an inherited mutation in SMARCA4 may also qualify for specific treatments or clinical trials.
If you have a SMARCA4 mutation, try to find a team of doctors with experience in genetics and rare hereditary cancer syndromes.
Other considerations
Some mutations in the SMARCA4 gene have been found to cause Coffin-Siris syndrome. This condition is characterized by delayed development, abnormalities of the fifth (pinky) fingers or toes, hearing impairment and eye abnormalities. Coffin-Siris syndrome is typically diagnosed in infancy.
Ask your doctor
If you or a family member has a mutation in SMARCA4, 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 SMARCA4 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 SMARCA4 mutation.