Human natural killer (NK) cells may be affected by inborn abnormalities that impact their development, function, or both. There are two types of NK cell development genetic abnormalities, depending on whether the deficit appears to be exclusive to NK cells or impacts several hematopoietic lineages. Recent work in the genetic dissection of these NK deficits is reviewed here (NKDs). Patients with severe combined immunodeficiencies who have mutations in the genes for adenosine deaminase, adenylate kinase 2, interleukin-2 receptor gamma chain, and Janus kinase 3 have NKDs and are susceptible to a variety of infections. Patients with GATA binding protein 2 deficiency have NKDs and a paucity of monocytes, making them vulnerable to both mycobacterial and viral infections. Rare people with minichromosome maintenance 4 deficiency have an NKD that appears to be related to viral infections, but they also have nonhematopoietic characteristics including adrenal insufficiency and growth retardation. 

The genetic dissection of the formation of human NK cells has begun as a result of these investigations. Additional research is needed, particularly in the hunt for the genetic origins of NKD. It might lead to the discovery of chemicals that influence the growth of NK cells, as well as a better understanding of the cells’ hitherto enigmatic function in humans.