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Genetics Home Reference: your guide to understanding genetic conditions
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PSENEN

Reviewed December 2013

What is the official name of the PSENEN gene?

The official name of this gene is “presenilin enhancer gamma secretase subunit.”

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

What is the normal function of the PSENEN gene?

The PSENEN gene provides instructions for making a protein called presenilin enhancer 2 or PEN-2. This protein is one part (subunit) of a complex called gamma- (γ-) secretase. PEN-2 processes another subunit of the complex, presenilin 1, which is produced from the PSEN1 gene. This step is necessary for the γ-secretase complex to be functional.

The γ-secretase complex is located in the membrane that surrounds cells, where it cuts apart (cleaves) many different proteins that span the cell membrane (transmembrane proteins). This cleavage is an important step in several chemical signaling pathways that transmit signals from outside the cell into the nucleus. One of these pathways, known as Notch signaling, is essential for the normal maturation and division of hair follicle cells and other types of skin cells. Notch signaling is also involved in normal immune system function.

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

hidradenitis suppurativa - caused by mutations in the PSENEN gene

At least three mutations in the PSENEN gene have been found to cause hidradenitis suppurativa, a chronic skin disease characterized by recurrent boil-like lumps (nodules) under the skin that develop in hair follicles. The nodules tend to become inflamed and painful, and they produce significant scarring as they heal.

PSENEN gene mutations reduce the amount of functional PEN-2 produced in cells, so less of this protein is available to act as part of the γ-secretase complex. The resulting shortage of normal γ-secretase impairs cell signaling pathways, including Notch signaling. Although little is known about the mechanism, studies suggest that abnormal Notch signaling may promote the development of recurrent nodules in hair follicles and trigger inflammation in the skin.

Where is the PSENEN gene located?

Cytogenetic Location: 19q13.12

Molecular Location on chromosome 19: base pairs 35,745,576 to 35,747,154

The PSENEN gene is located on the long (q) arm of chromosome 19 at position 13.12.

The PSENEN gene is located on the long (q) arm of chromosome 19 at position 13.12.

More precisely, the PSENEN gene is located from base pair 35,745,576 to base pair 35,747,154 on chromosome 19.

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 PSENEN?

You and your healthcare professional may find the following resources about PSENEN 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 PSENEN gene or gene products?

  • gamma-secretase subunit PEN-2
  • hematopoietic stem/progenitor cells protein MDS033
  • MDS033
  • MSTP064
  • PEN2
  • PEN-2
  • PEN2_HUMAN
  • presenilin enhancer 2 homolog

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 PSENEN?

cell ; cell membrane ; chronic ; enhancer ; gene ; hair follicle ; hematopoietic ; immune system ; inflammation ; nucleus ; progenitor cells ; protein ; subunit ; transmembrane

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

References

  • Melnik BC, Plewig G. Impaired Notch signalling: the unifying mechanism explaining the pathogenesis of hidradenitis suppurativa (acne inversa). Br J Dermatol. 2013 Apr;168(4):876-8. doi: 10.1111/bjd.12068. Epub 2013 Jan 31. (http://www.ncbi.nlm.nih.gov/pubmed/23020871?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/55851)
  • Pink AE, Simpson MA, Brice GW, Smith CH, Desai N, Mortimer PS, Barker JN, Trembath RC. PSENEN and NCSTN mutations in familial hidradenitis suppurativa (Acne Inversa). J Invest Dermatol. 2011 Jul;131(7):1568-70. doi: 10.1038/jid.2011.42. Epub 2011 Mar 17. (http://www.ncbi.nlm.nih.gov/pubmed/21412258?dopt=Abstract)
  • Pink AE, Simpson MA, Desai N, Dafou D, Hills A, Mortimer P, Smith CH, Trembath RC, Barker JN. Mutations in the γ-secretase genes NCSTN, PSENEN, and PSEN1 underlie rare forms of hidradenitis suppurativa (acne inversa). J Invest Dermatol. 2012 Oct;132(10):2459-61. doi: 10.1038/jid.2012.162. Epub 2012 May 24. (http://www.ncbi.nlm.nih.gov/pubmed/22622421?dopt=Abstract)
  • Pink AE, Simpson MA, Desai N, Trembath RC, Barker JN. γ-Secretase mutations in hidradenitis suppurativa: new insights into disease pathogenesis. J Invest Dermatol. 2013 Mar;133(3):601-7. doi: 10.1038/jid.2012.372. Epub 2012 Oct 25. Review. (http://www.ncbi.nlm.nih.gov/pubmed/23096707?dopt=Abstract)
  • Prokop S, Haass C, Steiner H. Length and overall sequence of the PEN-2 C-terminal domain determines its function in the stabilization of presenilin fragments. J Neurochem. 2005 Jul;94(1):57-62. (http://www.ncbi.nlm.nih.gov/pubmed/15953349?dopt=Abstract)
  • Wang B, Yang W, Wen W, Sun J, Su B, Liu B, Ma D, Lv D, Wen Y, Qu T, Chen M, Sun M, Shen Y, Zhang X. Gamma-secretase gene mutations in familial acne inversa. Science. 2010 Nov 19;330(6007):1065. doi: 10.1126/science.1196284. Epub 2010 Oct 7. (http://www.ncbi.nlm.nih.gov/pubmed/20929727?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: December 2013
Published: February 23, 2015