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Genetics Home Reference: your guide to understanding genetic conditions
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PSAP

Reviewed February 2013

What is the official name of the PSAP gene?

The official name of this gene is “prosaposin.”

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

What is the normal function of the PSAP gene?

The PSAP gene provides instructions for making a protein called prosaposin. This protein is involved in a number of biological functions, including the development of the nervous system and the reproductive system. Prosaposin is the precursor of four smaller proteins called saposin A, B, C, and D, which are produced when prosaposin is broken up (cleaved).

The individual saposins are found in cellular structures called lysosomes, which are the cell's recycling centers. The saposins help lysosomal enzymes break down fatty substances called sphingolipids.

The saposin B protein works with several enzymes to break down sphingolipids. Its most critical biological role seems to be associated with the enzyme arylsulfatase A. This enzyme is involved in breaking down a subgroup of sphingolipids called sulfatides, especially in the nervous system's white matter, which consists of nerve fibers covered by myelin. Myelin is a substance that insulates and protects nerves. Saposin B may also play a role in transporting lipids to the outer surface of the cell so they can be recognized by the immune system.

The saposin C protein works with the enzyme beta-glucocerebrosidase to break down another sphingolipid called glucocerebroside. Saposins A and D are also involved in processing sphingolipids.

Does the PSAP gene share characteristics with other genes?

The PSAP gene belongs to a family of genes called endogenous ligands (endogenous ligands).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

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

metachromatic leukodystrophy - caused by mutations in the PSAP gene

In a small number of individuals with metachromatic leukodystrophy, a disorder that causes deterioration of nervous system functions, researchers have identified PSAP gene mutations that result in a shortage (deficiency) of the saposin B protein. This deficiency interferes with the breakdown of sulfatides. As a result, these substances can accumulate to toxic levels in the nervous system.

The buildup of sulfatides gradually destroys myelin, the covering that protects nerves and promotes the efficient transmission of nerve impulses. Destruction of myelin leads to a loss of white matter (leukodystrophy) and impairment of nervous system function, resulting in the signs and symptoms of metachromatic leukodystrophy.

other disorders - caused by mutations in the PSAP gene

In a few individuals, mutations in the PSAP gene interfere with the function of the saposin C protein, resulting in a disorder that resembles a severe form of Gaucher disease. Signs and symptoms of this condition include neurological problems and abnormal enlargement of the liver and spleen (hepatosplenomegaly). Without adequate saposin C activator protein, the glucocerebrosidase enzyme cannot break down glucocerebroside effectively. As a result, glucocerebroside accumulates in the body's tissues as it does in the classic form of Gaucher disease. A few PSAP gene mutations have also been identified in individuals with signs and symptoms resembling another leukodystrophy called Krabbe disease.

In addition, a few mutations in the PSAP gene have been identified that prevent the production of more than one of the saposin proteins. Individuals with these mutations have massive accumulation of sphingolipids in their nervous system and other organs. This accumulation results in very severe neurological disease, respiratory problems, and hepatosplenomegaly.

Where is the PSAP gene located?

Cytogenetic Location: 10q21-q22

Molecular Location on chromosome 10: base pairs 71,816,297 to 71,851,324

The PSAP gene is located on the long (q) arm of chromosome 10 between positions 21 and 22.

The PSAP gene is located on the long (q) arm of chromosome 10 between positions 21 and 22.

More precisely, the PSAP gene is located from base pair 71,816,297 to base pair 71,851,324 on chromosome 10.

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 PSAP?

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

  • Prosaposin (sphingolipid activator protein-1)
  • prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy)
  • prosaptides
  • SAP1
  • SAP2 (sphingolipid activator protein-2)
  • SAP_HUMAN
  • SGP-1 (sulfoglycoprotein-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 PSAP?

breakdown ; cell ; deficiency ; enzyme ; gene ; hepatosplenomegaly ; immune system ; leukodystrophy ; nervous system ; neurological ; precursor ; protein ; respiratory ; toxic ; white matter

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

References

  • Al-Hassnan ZN, Al Dhalaan H, Patay Z, Faqeih E, Al-Owain M, Al-Duraihem A, Faiyaz-Ul-Haque M. Sphingolipid activator protein B deficiency: report of 9 Saudi patients and review of the literature. J Child Neurol. 2009 Dec;24(12):1513-9. doi: 10.1177/0883073809341269. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19955343?dopt=Abstract)
  • Basic Neurochemistry (sixth edition, 1999): Lysosomal Disease (http://www.ncbi.nlm.nih.gov/books/NBK28215/)
  • Deconinck N, Messaaoui A, Ziereisen F, Kadhim H, Sznajer Y, Pelc K, Nassogne MC, Vanier MT, Dan B. Metachromatic leukodystrophy without arylsulfatase A deficiency: a new case of saposin-B deficiency. Eur J Paediatr Neurol. 2008 Jan;12(1):46-50. Epub 2007 Jul 5. (http://www.ncbi.nlm.nih.gov/pubmed/17616409?dopt=Abstract)
  • Diaz-Font A, Cormand B, Santamaria R, Vilageliu L, Grinberg D, Chabás A. A mutation within the saposin D domain in a Gaucher disease patient with normal glucocerebrosidase activity. Hum Genet. 2005 Jul;117(2-3):275-7. Epub 2005 Apr 23. (http://www.ncbi.nlm.nih.gov/pubmed/15856305?dopt=Abstract)
  • Essentials of Glycobiology (first edition, 1999): Glycosphingolipid Degradation (http://www.ncbi.nlm.nih.gov/books/NBK20729/)
  • OMIM: GAUCHER DISEASE, ATYPICAL, DUE TO SAPOSIN C DEFICIENCY (http://omim.org/entry/610539)
  • Grossi S, Regis S, Rosano C, Corsolini F, Uziel G, Sessa M, Di Rocco M, Parenti G, Deodato F, Leuzzi V, Biancheri R, Filocamo M. Molecular analysis of ARSA and PSAP genes in twenty-one Italian patients with metachromatic leukodystrophy: identification and functional characterization of 11 novel ARSA alleles. Hum Mutat. 2008 Nov;29(11):E220-30. doi: 10.1002/humu.20851. (http://www.ncbi.nlm.nih.gov/pubmed/18693274?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/5660)
  • OMIM: PROSAPOSIN (http://omim.org/entry/176801)
  • Szymańska K, Ługowska A, Laure-Kamionowska M, Bekiesińska-Figatowska M, Gieruszczak-Białek D, Musielak M, Eichler S, Giese AK, Rolfs A. Diagnostic difficulties in Krabbe disease: a report of two cases and review of literature. Folia Neuropathol. 2012;50(4):346-56. Review. (http://www.ncbi.nlm.nih.gov/pubmed/23319190?dopt=Abstract)
  • Tamargo RJ, Velayati A, Goldin E, Sidransky E. The role of saposin C in Gaucher disease. Mol Genet Metab. 2012 Jul;106(3):257-63. doi: 10.1016/j.ymgme.2012.04.024. Epub 2012 May 5. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22652185?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: February 2013
Published: December 16, 2014