Health Topics
Official websites use .gov
A
.gov website belongs to an official government
organization in the United States.
Secure .gov websites use HTTPS
A
lock (
) or https:// means you’ve safely connected to
the .gov website. Share sensitive information only on official,
secure websites.
Normal Function
The FAT4 gene provides instructions for making a protein that plays an important role in the development of the brain, kidneys, and heart. The FAT4 protein is also important for the proper development and function of the lymphatic system, which is a network of vessels that transport white blood cells (lymphocytes), nutrients, and proteins in a fluid called lymph.
Research suggests that the FAT4 protein is involved in determining the position of cells and their components within various tissues. Proper cell positioning within a tissue allows cells to coordinate their activity and helps determine tissue structure and function.
The FAT4 protein may also act as a tumor suppressor, which means that it keeps cells from growing and dividing too rapidly or in an uncontrolled way.
Health Conditions Related to Genetic Changes
Hennekam syndrome
Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in the FAT4 gene have been found to cause Hennekam syndrome, an inherited disorder that is characterized by abnormalities of the lymphatic system. People with Hennekam syndrome often have lymphatic vessels that are dilated (lymphangiectasia) and an accumulation of lymph (lymphedema) in various tissues.
The pathogenic FAT4 gene variants that cause Hennekam syndrome interfere with the production of functional FAT4 proteins, which likely impairs the proper positioning of cells within the developing lymphatic vessels. This leads to a disruption in the formation and function of these vessels, resulting in the lymphangiectasia and lymphedema seen in people with Hennekam syndrome.
More About This Health ConditionOther disorders
Pathogenic variants in the FAT4 gene have also been found in individuals who have van Maldergem syndrome, a condition that is characterized by intellectual disabilities, hearing loss, skeletal abnormalities, and a brain malformation called periventricular heterotopia. In people with periventricular heterotopia, nerve cells do not migrate properly during early brain development. The pathogenic FAT4 gene variants that cause van Maldergem syndrome decrease the activity of the FAT4 protein, which likely disrupts the positioning of cells within the developing brain and other tissues. These changes contribute to the periventricular heterotopia and the other features seen in people with van Maldergem syndrome.
Pathogenic FAT4 gene variants have also been found in people with many types of cancers, including cancers of the pancreas, stomach, and brain. Many of the pathogenic FAT4 gene variants involved in these cancers are somatic, which means that they occur during a person's lifetime and are only found in certain cells. It is likely that these variants prevent the FAT4 protein from acting as a tumor suppressor, contributing to the uncontrollable growth and division of cells that is characteristic of cancer.
Other Names for This Gene
- cadherin-related family member 11
- CDHF14
- CDHR11
- FAT-J
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Alders M, Al-Gazali L, Cordeiro I, Dallapiccola B, Garavelli L, Tuysuz B, Salehi F, Haagmans MA, Mook OR, Majoie CB, Mannens MM, Hennekam RC. Hennekam syndrome can be caused by FAT4 mutations and be allelic to Van Maldergem syndrome. Hum Genet. 2014 Sep;133(9):1161-7. doi: 10.1007/s00439-014-1456-y. Epub 2014 Jun 7. Citation on PubMed
- Betterman KL, Sutton DL, Secker GA, Kazenwadel J, Oszmiana A, Lim L, Miura N, Sorokin L, Hogan BM, Kahn ML, McNeill H, Harvey NL. Atypical cadherin FAT4 orchestrates lymphatic endothelial cell polarity in response to flow. J Clin Invest. 2020 Jun 1;130(6):3315-3328. doi: 10.1172/JCI99027. Citation on PubMed
- Furukawa T, Sakamoto H, Takeuchi S, Ameri M, Kuboki Y, Yamamoto T, Hatori T, Yamamoto M, Sugiyama M, Ohike N, Yamaguchi H, Shimizu M, Shibata N, Shimizu K, Shiratori K. Whole exome sequencing reveals recurrent mutations in BRCA2 and FAT genes in acinar cell carcinomas of the pancreas. Sci Rep. 2015 Mar 6;5:8829. doi: 10.1038/srep08829. Citation on PubMed
- Mao W, Zhou J, Hu J, Zhao K, Fu Z, Wang J, Mao K. A pan-cancer analysis of FAT atypical cadherin 4 (FAT4) in human tumors. Front Public Health. 2022 Aug 16;10:969070. doi: 10.3389/fpubh.2022.969070. eCollection 2022. Citation on PubMed
- Zang ZJ, Cutcutache I, Poon SL, Zhang SL, McPherson JR, Tao J, Rajasegaran V, Heng HL, Deng N, Gan A, Lim KH, Ong CK, Huang D, Chin SY, Tan IB, Ng CC, Yu W, Wu Y, Lee M, Wu J, Poh D, Wan WK, Rha SY, So J, Salto-Tellez M, Yeoh KG, Wong WK, Zhu YJ, Futreal PA, Pang B, Ruan Y, Hillmer AM, Bertrand D, Nagarajan N, Rozen S, Teh BT, Tan P. Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes. Nat Genet. 2012 May;44(5):570-4. doi: 10.1038/ng.2246. Citation on PubMed
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.