Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

UNC13D

Reviewed January 2011

What is the official name of the UNC13D gene?

The official name of this gene is “unc-13 homolog D (C. elegans).”

UNC13D is the gene's official symbol. The UNC13D gene is also known by other names, listed below.

What is the normal function of the UNC13D gene?

The UNC13D gene provides instructions for making a protein that is involved in the process of cell destruction (cytolysis) and the regulation of the immune system.

The UNC13D protein is involved in the release of substances from cells (exocytosis). In particular, it is important for the exocytosis of structures called cytolytic granules from immune cells called T cells and NK cells. T cells and NK cells destroy other cells by secreting these cytolytic granules, which contain cell-killing proteins, onto the membranes of the target cells. The UNC13D protein helps transport these granules to the membrane of the target cell, allowing cytolytic proteins to enter the cell and trigger it to self-destruct.

This cytolytic mechanism also helps regulate the immune system by destroying unneeded T cells. Controlling the number of T cells prevents the overproduction of immune proteins called cytokines that lead to inflammation and which, in excess, cause tissue damage.

How are changes in the UNC13D gene related to health conditions?

familial hemophagocytic lymphohistiocytosis - caused by mutations in the UNC13D gene

More than 50 UNC13D gene mutations have been identified in people with familial hemophagocytic lymphohistiocytosis. Most of these mutations alter the way the gene's instructions are pieced together to produce the UNC13D protein, leading to a dysfunctional protein. The resulting shortage of functional UNC13D protein interferes with its role in cell destruction and immune system regulation, leading to the exaggerated immune response characteristic of familial hemophagocytic lymphohistiocytosis.

other disorders - course of condition modified by normal variations in the UNC13D gene

A variant (polymorphism) of the UNC13D gene has been associated with a higher risk of a complication called macrophage activation syndrome in people with systemic juvenile idiopathic arthritis (SJIA). SJIA is an autoimmune disorder that causes persistent joint inflammation beginning in childhood. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. Macrophage activation syndrome is a life-threatening complication of SJIA with symptoms similar to those of familial hemophagocytic lymphohistiocytosis, including fever, an enlarged liver and spleen, liver damage, and low numbers of blood cells.

The UNC13D gene variant associated with macrophage activation syndrome in people with SJIA consists of a specific combination of individual changes in 12 DNA building blocks (nucleotides). It is unknown how this genetic change results in an increased risk of this complication in affected individuals.

Where is the UNC13D gene located?

Cytogenetic Location: 17q25.1

Molecular Location on chromosome 17: base pairs 75,827,224 to 75,844,716

The UNC13D gene is located on the long (q) arm of chromosome 17 at position 25.1.

The UNC13D gene is located on the long (q) arm of chromosome 17 at position 25.1.

More precisely, the UNC13D gene is located from base pair 75,827,224 to base pair 75,844,716 on chromosome 17.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about UNC13D?

You and your healthcare professional may find the following resources about UNC13D helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the UNC13D gene or gene products?

  • FHL3
  • HLH3
  • HPLH3
  • Munc13-4
  • protein unc-13 homolog D
  • UN13D_HUMAN

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding UNC13D?

arthritis ; autoimmune ; cell ; complication ; DNA ; familial ; fever ; gene ; idiopathic ; immune response ; immune system ; inflammation ; joint ; joint inflammation ; juvenile ; macrophage ; NK cells ; polymorphism ; protein ; syndrome ; tissue

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Cetica V, Pende D, Griffiths GM, Aricò M. Molecular basis of familial hemophagocytic lymphohistiocytosis. Haematologica. 2010 Apr;95(4):538-41. doi: 10.3324/haematol.2009.019562. (http://www.ncbi.nlm.nih.gov/pubmed/20378576?dopt=Abstract)
  • Filipovich AH. Hemophagocytic lymphohistiocytosis and related disorders. Curr Opin Allergy Clin Immunol. 2006 Dec;6(6):410-5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17088644?dopt=Abstract)
  • Horne A, Ramme KG, Rudd E, Zheng C, Wali Y, al-Lamki Z, Gürgey A, Yalman N, Nordenskjöld M, Henter JI. Characterization of PRF1, STX11 and UNC13D genotype-phenotype correlations in familial hemophagocytic lymphohistiocytosis. Br J Haematol. 2008 Oct;143(1):75-83. doi: 10.1111/j.1365-2141.2008.07315.x. Epub 2008 Aug 15. (http://www.ncbi.nlm.nih.gov/pubmed/18710388?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/201294)
  • Pivot-Pajot C, Varoqueaux F, de Saint Basile G, Bourgoin SG. Munc13-4 regulates granule secretion in human neutrophils. J Immunol. 2008 May 15;180(10):6786-97. (http://www.ncbi.nlm.nih.gov/pubmed/18453599?dopt=Abstract)
  • Rudd E, Bryceson YT, Zheng C, Edner J, Wood SM, Ramme K, Gavhed S, Gürgey A, Hellebostad M, Bechensteen AG, Ljunggren HG, Fadeel B, Nordenskjöld M, Henter JI. Spectrum, and clinical and functional implications of UNC13D mutations in familial haemophagocytic lymphohistiocytosis. J Med Genet. 2008 Mar;45(3):134-41. Epub 2007 Nov 9. (http://www.ncbi.nlm.nih.gov/pubmed/17993578?dopt=Abstract)
  • Santoro A, Cannella S, Trizzino A, Bruno G, De Fusco C, Notarangelo LD, Pende D, Griffiths GM, Aricò M. Mutations affecting mRNA splicing are the most common molecular defect in patients with familial hemophagocytic lymphohistiocytosis type 3. Haematologica. 2008 Jul;93(7):1086-90. doi: 10.3324/haematol.12622. Epub 2008 May 19. (http://www.ncbi.nlm.nih.gov/pubmed/18492689?dopt=Abstract)
  • Zhang K, Biroschak J, Glass DN, Thompson SD, Finkel T, Passo MH, Binstadt BA, Filipovich A, Grom AA. Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms. Arthritis Rheum. 2008 Sep;58(9):2892-6. doi: 10.1002/art.23734. (http://www.ncbi.nlm.nih.gov/pubmed/18759271?dopt=Abstract)
  • Zur Stadt U, Beutel K, Kolberg S, Schneppenheim R, Kabisch H, Janka G, Hennies HC. Mutation spectrum in children with primary hemophagocytic lymphohistiocytosis: molecular and functional analyses of PRF1, UNC13D, STX11, and RAB27A. Hum Mutat. 2006 Jan;27(1):62-8. (http://www.ncbi.nlm.nih.gov/pubmed/16278825?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: January 2011
Published: November 24, 2014