Reviewed December 2008
What is the official name of the PSEN2 gene?
The official name of this gene is “presenilin 2.”
PSEN2 is the gene's official symbol. The PSEN2 gene is also known by other names, listed below.
What is the normal function of the PSEN2 gene?
The PSEN2 gene provides instructions for making a protein called presenilin 2. Presenilin 2 helps process proteins that transmit chemical signals from the cell membrane into the nucleus. Once in the nucleus, these signals turn on (activate) genes that are important for cell growth and maturation.
Presenilin 2 is best known for its role in processing amyloid precursor protein, which is found in the brain and other tissues. Research suggests that presenilin 2 works together with other enzymes to cut amyloid precursor protein into smaller segments (peptides). One of these peptides is called soluble amyloid precursor protein (sAPP), and another is called amyloid beta peptide. Recent evidence suggests that sAPP has growth-promoting properties and may play a role in the formation of neurons in the brain both before and after birth. Other functions of sAPP and amyloid beta peptide are under investigation.
How are changes in the PSEN2 gene related to health conditions?
- Alzheimer disease - caused by mutations in the PSEN2 gene
At least 11 mutations in the PSEN2 gene have been shown to cause early-onset Alzheimer disease. Mutations in this gene account for less than 5 percent of all early-onset cases of the disorder.
Two of the most common PSEN2 mutations that cause early-onset Alzheimer disease change single protein building blocks (amino acids) used to make presenilin 2. One mutation replaces the amino acid asparagine with the amino acid isoleucine at position 141 (written as Asn141Ile or N141I). The other mutation changes the amino acid methionine to the amino acid valine at position 239 (written as Met239Val or M239V). These mutations appear to disrupt the processing of amyloid precursor protein, leading to the overproduction of amyloid beta peptide. This protein fragment can build up in the brain and form clumps called amyloid plaques that are characteristic of Alzheimer disease. A buildup of toxic amyloid beta peptide and amyloid plaques may lead to the death of neurons and the progressive signs and symptoms of this disorder.
Where is the PSEN2 gene located?
Cytogenetic Location: 1q42.13
Molecular Location on chromosome 1: base pairs 226,870,572 to 226,896,103
(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI (http://www.ncbi.nlm.nih.gov/gene/5664))
The PSEN2 gene is located on the long (q) arm of chromosome 1 at position 42.13.
More precisely, the PSEN2 gene is located from base pair 226,870,572 to base pair 226,896,103 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 PSEN2?
You and your healthcare professional may find the following resources about PSEN2 helpful.
- Educational resources - Information pages
Basic Neurochemistry: Molecular, Cellular, and Medical Aspects (sixth edition, 2006): Alzheimer's Disease Is the Most Common Neurodegenerative Disorder (http://www.ncbi.nlm.nih.gov/books/NBK27944/)
- Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1236)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for PSEN2 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=5664%5Bgeneid%5D)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=%28%28PSEN2%5BTIAB%5D%29%20OR%20%28presenilin%202%5BTIAB%5D%29%29%20AND%20%28%28Genes%5BMH%5D%29%20OR%20%28Genetic%20Phenomena%5BMH%5D%29%29%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201080%20days%22%5Bdp%5D)
- OMIM - Genetic disorder catalog (http://omim.org/entry/600759)
Research Resources - Tools for researchers
- Alzheimer Disease & Frontotemporal Dementia Mutation Database (http://www.molgen.ua.ac.be/ADmutations/Default.cfm?MT=1&ML=1&Page=MutByQuery&Query=tblContexts.ID=2&Selection=Gene%20=%20PSEN2)
- Alzheimer Research Forum: AlzGene database (http://www.alzgene.org/geneoverview.asp?geneid=55)
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/PSEN2ID41883ch1q42.html)
- HGNC Gene Symbol Report (http://www.genenames.org/cgi-bin/gene_symbol_report?q=data/hgnc_data.php&hgnc_id=9509)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5664)
What other names do people use for the PSEN2 gene or gene products?
- AD3-like protein
- Alzheimer's disease 3-like
- presenilin 2 (Alzheimer disease 4)
- PS2 protein (alzheimer-associated)
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 PSEN2?
amino acid ;
cell membrane ;
You may find definitions for these and many other terms in the Genetics Home Reference
- Bertram L, Tanzi RE. The current status of Alzheimer's disease genetics: what do we tell the patients? Pharmacol Res. 2004 Oct;50(4):385-96. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15304236?dopt=Abstract)
- Cordy JM, Hooper NM, Turner AJ. The involvement of lipid rafts in Alzheimer's disease. Mol Membr Biol. 2006 Jan-Feb;23(1):111-22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16611586?dopt=Abstract)
- George-Hyslop PS, Rossor M. Alzheimer's disease. Unravelling the disease process. Lancet. 2001 Dec;358 Suppl:S1. (http://www.ncbi.nlm.nih.gov/pubmed/11784550?dopt=Abstract)
- Harman D. Alzheimer's disease pathogenesis: role of aging. Ann N Y Acad Sci. 2006 May;1067:454-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16804026?dopt=Abstract)
- NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5664)
- Papassotiropoulos A, Fountoulakis M, Dunckley T, Stephan DA, Reiman EM. Genetics, transcriptomics, and proteomics of Alzheimer's disease. J Clin Psychiatry. 2006 Apr;67(4):652-70. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16669732?dopt=Abstract)
- Rocchi A, Pellegrini S, Siciliano G, Murri L. Causative and susceptibility genes for Alzheimer's disease: a review. Brain Res Bull. 2003 Jun 30;61(1):1-24. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12788204?dopt=Abstract)
- Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001 Apr;81(2):741-66. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11274343?dopt=Abstract)
- St George-Hyslop PH. Genetic factors in the genesis of Alzheimer's disease. Ann N Y Acad Sci. 2000;924:1-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11193785?dopt=Abstract)
- Thinakaran G, Parent AT. Identification of the role of presenilins beyond Alzheimer's disease. Pharmacol Res. 2004 Oct;50(4):411-8. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15304238?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
See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.