The AMER1 gene provides instructions for making a protein found in tissues throughout the body where it helps regulate the Wnt signaling pathway, which is a series of chemical signals that affect the way cells and tissues develop. Wnt signaling is important for cell division, attachment of cells to one another (adhesion), cell movement (migration), and many other cell activities. The AMER1 protein can promote cell growth by helping to turn on (activate) the Wnt pathway or prevent cell growth by helping to turn off (repress) the Wnt pathway. When repressing the pathway, the AMER1 protein is acting as a tumor suppressor, which means that it helps prevent cells from growing and dividing (proliferating) too rapidly or in an uncontrolled way.
Health Conditions Related to Genetic Changes
Mutations in the AMER1 gene have been found in Wilms tumor, a rare form of kidney cancer that occurs almost exclusively in children. These mutations are somatic, meaning that they are acquired during a person's lifetime and are present only in kidney cells that give rise to the tumor. AMER1 gene mutations result in a protein with a reduced ability to repress Wnt signaling. As a result, Wnt signaling is increased, which leads to the unchecked proliferation of kidney cells and tumor development.More About This Health Condition
Mutations in the AMER1 gene that are present in cells throughout the body (called germline mutations) cause a bone disorder called osteopathia striata with cranial sclerosis. This condition occurs almost exclusively in females because males with the disorder usually die before or soon after birth. Affected females have excessive bone growth (hyperostosis), which leads to multiple skeletal abnormalities including an unusually large head (macrocephaly) and abnormal facial features. Males who survive infancy have bone abnormalities and heart, gastrointestinal, and genitourinary malformations. AMER1 gene mutations that cause osteopathia striata with cranial sclerosis lead to a lack of functional AMER1 protein, disrupting its role in regulating the Wnt signaling pathway. It is unclear why these mutations primarily affect skeletal development.
In addition to Wilms tumor (described above), changes in the AMER1 gene have been reported to be associated with many other cancers. These mutations are somatic and are present only in cells that give rise to cancer. Studies have shown that AMER1 gene changes are associated with stomach (gastric), breast, and colorectal cancers. It is likely that these gene changes impair the protein's tumor suppressor function, allowing cells to proliferate without control or order, which leads to cancer development.
Other Names for This Gene
- adenomatous polyposis coli membrane recruitment 1
- family with sequence similarity 123B
- protein FAM123B
- Wilms tumor gene on the X chromosome protein
- Wilms tumor on the X
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
- Gear R, Savarirayan R. Osteopathia Striata with Cranial Sclerosis. 2021 Apr 15. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from http://www.ncbi.nlm.nih.gov/books/NBK569515/ Citation on PubMed
- Jenkins ZA, van Kogelenberg M, Morgan T, Jeffs A, Fukuzawa R, Pearl E, Thaller C, Hing AV, Porteous ME, Garcia-Minaur S, Bohring A, Lacombe D, Stewart F, Fiskerstrand T, Bindoff L, Berland S, Ades LC, Tchan M, David A, Wilson LC, Hennekam RC, Donnai D, Mansour S, Cormier-Daire V, Robertson SP. Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis. Nat Genet. 2009 Jan;41(1):95-100. doi: 10.1038/ng.270. Epub 2008 Dec 14. Citation on PubMed
- Perdu B, de Freitas F, Frints SG, Schouten M, Schrander-Stumpel C, Barbosa M, Pinto-Basto J, Reis-Lima M, de Vernejoul MC, Becker K, Freckmann ML, Keymolen K, Haan E, Savarirayan R, Koenig R, Zabel B, Vanhoenacker FM, Van Hul W. Osteopathia striata with cranial sclerosis owing to WTX gene defect. J Bone Miner Res. 2010 Jan;25(1):82-90. doi: 10.1359/jbmr.090707. Citation on PubMed
- Sanz-Pamplona R, Lopez-Doriga A, Pare-Brunet L, Lazaro K, Bellido F, Alonso MH, Ausso S, Guino E, Beltran S, Castro-Giner F, Gut M, Sanjuan X, Closa A, Cordero D, Moron-Duran FD, Soriano A, Salazar R, Valle L, Moreno V. Exome Sequencing Reveals AMER1 as a Frequently Mutated Gene in Colorectal Cancer. Clin Cancer Res. 2015 Oct 15;21(20):4709-18. doi: 10.1158/1078-0432.CCR-15-0159. Epub 2015 Jun 12. Citation on PubMed or Free article on PubMed Central
- Zhang YY, Wang QM, Niu HL, Liu X, Zhang QL. The General Expression Analysis of WTX Gene in Normal and Cancer Tissues. Pathol Oncol Res. 2017 Apr;23(2):439-446. doi: 10.1007/s12253-016-0168-0. Epub 2016 Dec 28. Citation on PubMed