The KHDC3L gene provides instructions for making a protein whose role is not known. The KHDC3L protein is thought to be involved in regulating gene activity (expression) through a phenomenon known as genomic imprinting. Through genomic imprinting, certain genes are turned off (inactivated) based on which parent the copy of the gene came from. For most genes, both copies of the gene (one copy inherited from each parent) are active in all cells. However, for a small subset of genes, only one of the two copies is active and the other is turned off. For some of these genes, the copy from the father is normally active, while for others, the copy from the mother is normally active.
It is likely that the KHDC3L protein has additional roles in egg cell (oocyte) and embryonic development; however, its exact functions are unclear.
Health Conditions Related to Genetic Changes
Recurrent hydatidiform mole
At least six mutations in the KHDC3L gene have been found to cause a pregnancy-related condition known as recurrent hydatidiform mole. A hydatidiform mole is a mass that forms early in pregnancy and is made up of cells from an abnormally developed embryo and placenta. The placenta, a structure in the uterus that normally provides nutrients to a growing fetus, is dysfunctional and appears as numerous small sacs, often described as resembling a bunch of grapes. When a hydatidiform mole develops more than once, the condition is known as recurrent hydatidiform mole. KHDC3L gene mutations account for recurrent hydatidiform mole in about 5 percent of women with this condition.
KHDC3L gene mutations result in the production of a protein with reduced function. As a result, oocytes do not develop normally. A pregnancy that results from an abnormal oocyte cannot develop properly, resulting in recurrent hydatidiform mole. KHDC3L gene mutations can also prevent proper imprinting of multiple genes that contribute to a developing embryo, leading to abnormal gene activity (expression). It is not clear if problems with imprinting also contribute to the development of a hydatidiform mole. In women with KHDC3L gene mutations, a hydatidiform mole will develop in every pregnancy that occurs with her egg cells.More About This Health Condition
Other Names for This Gene
- ES cell-associated transcript 1 protein
- KH domain containing 3-like, subcortical maternal complex member
- KHDC3-like protein
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Fallahian M, Sebire NJ, Savage PM, Seckl MJ, Fisher RA. Mutations in NLRP7 and KHDC3L confer a complete hydatidiform mole phenotype on digynic triploid conceptions. Hum Mutat. 2013 Feb;34(2):301-8. doi: 10.1002/humu.22228. Epub 2012 Nov 2. Citation on PubMed
- Hui P, Buza N, Murphy KM, Ronnett BM. Hydatidiform Moles: Genetic Basis and Precision Diagnosis. Annu Rev Pathol. 2017 Jan 24;12:449-485. doi: 10.1146/annurev-pathol-052016-100237. Review. Citation on PubMed
- Nguyen NM, Slim R. Genetics and Epigenetics of Recurrent Hydatidiform Moles: Basic Science and Genetic Counselling. Curr Obstet Gynecol Rep. 2014 Jan 21;3:55-64. eCollection 2014. Review. Citation on PubMed or Free article on PubMed Central
- Parry DA, Logan CV, Hayward BE, Shires M, Landolsi H, Diggle C, Carr I, Rittore C, Touitou I, Philibert L, Fisher RA, Fallahian M, Huntriss JD, Picton HM, Malik S, Taylor GR, Johnson CA, Bonthron DT, Sheridan EG. Mutations causing familial biparental hydatidiform mole implicate c6orf221 as a possible regulator of genomic imprinting in the human oocyte. Am J Hum Genet. 2011 Sep 9;89(3):451-8. doi: 10.1016/j.ajhg.2011.08.002. Epub 2011 Sep 1. Citation on PubMed or Free article on PubMed Central
- Reddy R, Akoury E, Phuong Nguyen NM, Abdul-Rahman OA, Dery C, Gupta N, Daley WP, Ao A, Landolsi H, Ann Fisher R, Touitou I, Slim R. Report of four new patients with protein-truncating mutations in C6orf221/KHDC3L and colocalization with NLRP7. Eur J Hum Genet. 2013 Sep;21(9):957-64. doi: 10.1038/ejhg.2012.274. Epub 2012 Dec 12. Citation on PubMed or Free article on PubMed Central