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 FAM83H gene provides instructions for making a protein that is found in cells throughout the body. The FAM83H protein interacts with other proteins in the fluid-filled space inside the cell (the cytoplasm) to help maintain the cell's structure (cytoskeleton).
High levels of the FAM83H protein are found in specialized tooth cells called ameloblasts. Ameloblasts produce tooth enamel, which is the hard, white material that forms the protective outer layer of each tooth. The FAM83H protein plays a role in regulating many cellular processes during enamel formation.
Health Conditions Related to Genetic Changes
Amelogenesis imperfecta
Variants (also called mutations) in the FAM83H gene have been found to cause a disorder called amelogenesis imperfecta. In people with this disorder, tooth enamel does not form properly. As a result, people with amelogenesis imperfecta may have teeth that are unusually small, discolored, pitted, or grooved. When this condition is caused by FAM83H gene variants, it is inherited in an autosomal dominant pattern, which means that one copy of the gene in each cell is altered.
Most of the FAM83H gene variants that cause amelogenesis imperfecta lead to the insertion of a premature stop signal in the genetic instructions for making the FAM83H protein. As a result, cells produce an abnormally short version of the protein. While the normal FAM83H protein is found in the cytoplasm, the shortened protein is found in the cell's nucleus. The altered protein is thought to trap other proteins within the nucleus, not allowing them to go into the cytoplasm where they are needed. Because this version of the FAM83H protein interferes with normal cell activities, the variants are described as "dominant-negative variants." Within ameloblasts, these trapped proteins likely lead to problems with the structure of the cell, which can cause the weak enamel and the fragile and discolored teeth seen in people with amelogenesis imperfecta.
More About This Health ConditionOther Names for This Gene
- AI3
- FA83H_HUMAN
- FAM83H variant 1
- family with sequence similarity 83, member H
- FLJ46072
- protein FAM83H
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Kim JW, Lee SK, Lee ZH, Park JC, Lee KE, Lee MH, Park JT, Seo BM, Hu JC, Simmer JP. FAM83H mutations in families with autosomal-dominant hypocalcified amelogenesis imperfecta. Am J Hum Genet. 2008 Feb;82(2):489-94. doi: 10.1016/j.ajhg.2007.09.020. Citation on PubMed or Free article on PubMed Central
- Kuga T, Sasaki M, Mikami T, Miake Y, Adachi J, Shimizu M, Saito Y, Koura M, Takeda Y, Matsuda J, Tomonaga T, Nakayama Y. FAM83H and casein kinase I regulate the organization of the keratin cytoskeleton and formation of desmosomes. Sci Rep. 2016 May 25;6:26557. doi: 10.1038/srep26557. Citation on PubMed
- Lee SK, Hu JC, Bartlett JD, Lee KE, Lin BP, Simmer JP, Kim JW. Mutational spectrum of FAM83H: the C-terminal portion is required for tooth enamel calcification. Hum Mutat. 2008 Aug;29(8):E95-9. doi: 10.1002/humu.20789. Citation on PubMed or Free article on PubMed Central
- Lee SK, Lee KE, Jeong TS, Hwang YH, Kim S, Hu JC, Simmer JP, Kim JW. FAM83H mutations cause ADHCAI and alter intracellular protein localization. J Dent Res. 2011 Mar;90(3):377-81. doi: 10.1177/0022034510389177. Epub 2010 Nov 30. Citation on PubMed
- Tachie-Menson T, Gazquez-Gutierrez A, Fulcher LJ, Macartney TJ, Wood NT, Varghese J, Gourlay R, Soares RF, Sapkota GP. Characterisation of the biochemical and cellular roles of native and pathogenic amelogenesis imperfecta mutants of FAM83H. Cell Signal. 2020 Aug;72:109632. doi: 10.1016/j.cellsig.2020.109632. Epub 2020 Apr 11. Citation on PubMed
- Wang SK, Zhang H, Hu CY, Liu JF, Chadha S, Kim JW, Simmer JP, Hu JCC. FAM83H and Autosomal Dominant Hypocalcified Amelogenesis Imperfecta. J Dent Res. 2021 Mar;100(3):293-301. doi: 10.1177/0022034520962731. Epub 2020 Oct 9. 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.