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Genetics Home Reference: your guide to understanding genetic conditions
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POMT2

Reviewed August 2013

What is the official name of the POMT2 gene?

The official name of this gene is “protein-O-mannosyltransferase 2.”

POMT2 is the gene's official symbol. The POMT2 gene is also known by other names, listed below.

What is the normal function of the POMT2 gene?

The POMT2 gene provides instructions for making one piece of the protein O-mannosyltransferase (POMT) enzyme complex. The other piece is produced from the POMT1 gene. This enzyme complex is present in many different tissues in the body but is particularly abundant in skeletal muscles, fetal brain, and testes.

The POMT complex helps modify a protein called alpha (α)-dystroglycan. Specifically, this complex adds a sugar molecule called mannose to α-dystroglycan through a process called glycosylation. Glycosylation is critical for the normal function of α-dystroglycan.

The α-dystroglycan protein helps anchor the structural framework inside each cell (cytoskeleton) to the lattice of proteins and other molecules outside the cell (extracellular matrix). In skeletal muscles, glycosylated α-dystroglycan helps stabilize and protect muscle fibers. In the brain, it helps direct the movement (migration) of nerve cells (neurons) during early development.

Does the POMT2 gene share characteristics with other genes?

The POMT2 gene belongs to a family of genes called dolichyl D-mannosyl phosphate dependent mannosyltransferases (dolichyl D-mannosyl phosphate dependent mannosyltransferases).

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 POMT2 gene related to health conditions?

Walker-Warburg syndrome - caused by mutations in the POMT2 gene

Mutations in the POMT2 gene cause Walker-Warburg syndrome in a small number of people. This condition is the most severe form of a group of disorders known as congenital muscular dystrophies. Walker-Warburg syndrome causes muscle weakness and abnormalities of the brain and eyes. Because of the severity of the problems caused by this condition, affected individuals usually do not survive past early childhood.

POMT2 gene mutations that cause Walker-Warburg syndrome lead to the formation of nonfunctional POMT enzyme complexes that cannot transfer mannose to α-dystroglycan. As a result, α-dystroglycan, which is said to be hypoglycosylated, can no longer effectively anchor cells to the proteins and other molecules that surround them. Without functional α-dystroglycan to stabilize muscle cells, muscle fibers become damaged as they repeatedly contract and relax with use. The damaged fibers weaken and die over time, which affects the development, structure, and function of skeletal muscles in people with Walker-Warburg syndrome.

Defective α-dystroglycan also affects the migration of neurons during the early development of the brain. Instead of stopping when they reach their intended destinations, some neurons migrate past the surface of the brain into the fluid-filled space that surrounds it. Researchers believe that this problem with neuronal migration causes a brain abnormality called cobblestone lissencephaly, in which the surface of the brain lacks the normal folds and grooves and instead appears bumpy and irregular. Less is known about the effects of POMT2 gene mutations in other parts of the body.

other disorders - caused by mutations in the POMT2 gene

Mutations in the POMT2 gene are also involved in less severe forms of muscular dystrophy, including muscle-eye-brain disease, POMT2-related congenital muscular dystrophy, and limb-girdle muscular dystrophy type 2N (LGMD2N). Muscle-eye-brain disease is similar to Walker-Warburg syndrome, although affected individuals usually survive into childhood or adolescence. POMT2-related congenital muscular dystrophy causes muscle weakness, brain abnormalities, and intellectual disability, but usually does not affect the eyes. LGMD2N is the mildest of the conditions caused by changes in the POMT2 gene. Individuals with this condition have muscle weakness in the arms and legs that begins in childhood and leads to difficulty walking; however, the brain and eyes are not affected.

POMT2 gene mutations that cause these conditions result in POMT enzyme complexes with reduced function. As a result, glycosylation of α-dystroglycan is impaired. The severity of the resulting condition appears to be related to the level of α-dystroglycan glycosylation; the less glycosylation, the more severe the condition.

Where is the POMT2 gene located?

Cytogenetic Location: 14q24

Molecular Location on chromosome 14: base pairs 77,274,955 to 77,320,881

The POMT2 gene is located on the long (q) arm of chromosome 14 at position 24.

The POMT2 gene is located on the long (q) arm of chromosome 14 at position 24.

More precisely, the POMT2 gene is located from base pair 77,274,955 to base pair 77,320,881 on chromosome 14.

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 POMT2?

You and your healthcare professional may find the following resources about POMT2 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 POMT2 gene or gene products?

  • dolichyl-phosphate-mannose--protein mannosyltransferase 2
  • LGMD2N
  • MDDGA2
  • MDDGB2
  • MDDGC2
  • POMT2_HUMAN
  • protein O-mannosyl-transferase 2

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 POMT2?

cell ; congenital ; cytoskeleton ; disability ; enzyme ; extracellular ; extracellular matrix ; gene ; glycosylation ; mannose ; molecule ; muscle cells ; muscular dystrophy ; neuronal migration ; phosphate ; protein ; syndrome ; testes ; transferase

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

References

  • Akasaka-Manya K, Manya H, Nakajima A, Kawakita M, Endo T. Physical and functional association of human protein O-mannosyltransferases 1 and 2. J Biol Chem. 2006 Jul 14;281(28):19339-45. Epub 2006 May 12. (http://www.ncbi.nlm.nih.gov/pubmed/16698797?dopt=Abstract)
  • Biancheri R, Falace A, Tessa A, Pedemonte M, Scapolan S, Cassandrini D, Aiello C, Rossi A, Broda P, Zara F, Santorelli FM, Minetti C, Bruno C. POMT2 gene mutation in limb-girdle muscular dystrophy with inflammatory changes. Biochem Biophys Res Commun. 2007 Nov 30;363(4):1033-7. Epub 2007 Sep 25. (http://www.ncbi.nlm.nih.gov/pubmed/17923109?dopt=Abstract)
  • Manya H, Chiba A, Yoshida A, Wang X, Chiba Y, Jigami Y, Margolis RU, Endo T. Demonstration of mammalian protein O-mannosyltransferase activity: coexpression of POMT1 and POMT2 required for enzymatic activity. Proc Natl Acad Sci U S A. 2004 Jan 13;101(2):500-5. Epub 2003 Dec 29. (http://www.ncbi.nlm.nih.gov/pubmed/14699049?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/29954)
  • OMIM: PROTEIN O-MANNOSYLTRANSFERASE 2 (http://omim.org/entry/607439)
  • van Reeuwijk J, Janssen M, van den Elzen C, Beltran-Valero de Bernabé D, Sabatelli P, Merlini L, Boon M, Scheffer H, Brockington M, Muntoni F, Huynen MA, Verrips A, Walsh CA, Barth PG, Brunner HG, van Bokhoven H. POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker-Warburg syndrome. J Med Genet. 2005 Dec;42(12):907-12. Epub 2005 May 13. (http://www.ncbi.nlm.nih.gov/pubmed/15894594?dopt=Abstract)
  • Yanagisawa A, Bouchet C, Quijano-Roy S, Vuillaumier-Barrot S, Clarke N, Odent S, Rodriguez D, Romero NB, Osawa M, Endo T, Taratuto AL, Seta N, Guicheney P. POMT2 intragenic deletions and splicing abnormalities causing congenital muscular dystrophy with mental retardation. Eur J Med Genet. 2009 Jul-Aug;52(4):201-6. doi: 10.1016/j.ejmg.2008.12.004. Epub 2008 Dec 27. (http://www.ncbi.nlm.nih.gov/pubmed/19138766?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: August 2013
Published: September 15, 2014