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Genetics Home Reference: your guide to understanding genetic conditions
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NCSTN

Reviewed December 2013

What is the official name of the NCSTN gene?

The official name of this gene is “nicastrin.”

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

What is the normal function of the NCSTN gene?

The NCSTN gene provides instructions for making a protein called nicastrin. This protein is one part (subunit) of a complex called gamma- (γ-) secretase. Nicastrin plays a critical role in the assembly and stability of this complex.

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 NCSTN gene related to health conditions?

hidradenitis suppurativa - caused by mutations in the NCSTN gene

At least 11 mutations in the NCSTN 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.

NCSTN gene mutations reduce the amount of functional nicastrin 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 NCSTN gene located?

Cytogenetic Location: 1q22-q23

Molecular Location on chromosome 1: base pairs 160,343,272 to 160,358,951

The NCSTN gene is located on the long (q) arm of chromosome 1 between positions 22 and 23.

The NCSTN gene is located on the long (q) arm of chromosome 1 between positions 22 and 23.

More precisely, the NCSTN gene is located from base pair 160,343,272 to base pair 160,358,951 on chromosome 1.

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 NCSTN?

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

  • anterior pharynx-defective 2
  • APH2
  • ATAG1874
  • KIAA0253
  • NICA_HUMAN
  • nicastrin precursor
  • RP11-517F10.1

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 NCSTN?

anterior ; cell ; cell membrane ; chronic ; gene ; hair follicle ; immune system ; inflammation ; nucleus ; precursor ; protein ; subunit ; transmembrane

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

References

  • Liu Y, Gao M, Lv YM, Yang X, Ren YQ, Jiang T, Zhang X, Guo BR, Li M, Zhang Q, Zhang P, Zhou FS, Chen G, Yin XY, Zuo XB, Sun LD, Zheng XD, Zhang SM, Liu JJ, Zhou Y, Li YR, Wang J, Wang J, Yang HM, Yang S, Li RQ, Zhang XJ. Confirmation by exome sequencing of the pathogenic role of NCSTN mutations in acne inversa (hidradenitis suppurativa). J Invest Dermatol. 2011 Jul;131(7):1570-2. doi: 10.1038/jid.2011.62. Epub 2011 Mar 24. (http://www.ncbi.nlm.nih.gov/pubmed/21430701?dopt=Abstract)
  • 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/23385)
  • 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)
  • 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: December 16, 2014