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Genetics Home Reference: your guide to understanding genetic conditions
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POMT1

Reviewed August 2013

What is the official name of the POMT1 gene?

The official name of this gene is “protein-O-mannosyltransferase 1.”

POMT1 is the gene's official symbol. The POMT1 gene is also known by other names, listed below.

What is the normal function of the POMT1 gene?

The POMT1 gene provides instructions for making one piece of the protein O-mannosyltransferase (POMT) enzyme complex. The other piece is produced from the POMT2 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 POMT1 gene share characteristics with other genes?

The POMT1 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 POMT1 gene related to health conditions?

Walker-Warburg syndrome - caused by mutations in the POMT1 gene

Mutations in the POMT1 gene cause Walker-Warburg syndrome, the most severe form of a group of disorders known as congenital muscular dystrophies. Individuals with Walker-Warburg syndrome have 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.

POMT1 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 POMT1 gene mutations in other parts of the body.

other disorders - caused by mutations in the POMT1 gene

Mutations in the POMT1 gene are also involved in less severe forms of muscular dystrophy, including muscle-eye-brain disease, POMT1-related congenital muscular dystrophy, and limb-girdle muscular dystrophy type 2K (LGMD2K). Muscle-eye-brain disease is similar to Walker-Warburg syndrome, although affected individuals usually survive into childhood or adolescence. POMT1-related congenital muscular dystrophy causes muscle weakness, brain abnormalities, and intellectual disability, but usually does not affect the eyes. LGMD2K is the mildest of the conditions caused by changes in the POMT1 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.

POMT1 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 POMT1 gene located?

Cytogenetic Location: 9q34.1

Molecular Location on chromosome 9: base pairs 131,502,894 to 131,523,805

The POMT1 gene is located on the long (q) arm of chromosome 9 at position 34.1.

The POMT1 gene is located on the long (q) arm of chromosome 9 at position 34.1.

More precisely, the POMT1 gene is located from base pair 131,502,894 to base pair 131,523,805 on chromosome 9.

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 POMT1?

You and your healthcare professional may find the following resources about POMT1 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 POMT1 gene or gene products?

  • dolichyl-phosphate-mannose-protein mannosyltransferase
  • dolichyl-phosphate-mannose--protein mannosyltransferase 1
  • LGMD2K
  • MDDGA1
  • MDDGB1
  • MDDGC1
  • POMT1_HUMAN
  • protein O-mannosyl-transferase 1
  • RT

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 POMT1?

cell ; congenital ; cytoskeleton ; disability ; enzyme ; extracellular ; extracellular matrix ; gene ; glycosylation ; mannose ; molecule ; muscular dystrophy ; phosphate ; protein ; RT ; syndrome ; testes ; transferase

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

References

  • Akasaka-Manya K, Manya H, Endo T. Mutations of the POMT1 gene found in patients with Walker-Warburg syndrome lead to a defect of protein O-mannosylation. Biochem Biophys Res Commun. 2004 Dec 3;325(1):75-9. (http://www.ncbi.nlm.nih.gov/pubmed/15522202?dopt=Abstract)
  • 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)
  • Balci B, Uyanik G, Dincer P, Gross C, Willer T, Talim B, Haliloglu G, Kale G, Hehr U, Winkler J, Topaloğlu H. An autosomal recessive limb girdle muscular dystrophy (LGMD2) with mild mental retardation is allelic to Walker-Warburg syndrome (WWS) caused by a mutation in the POMT1 gene. Neuromuscul Disord. 2005 Apr;15(4):271-5. (http://www.ncbi.nlm.nih.gov/pubmed/15792865?dopt=Abstract)
  • Bello L, Melacini P, Pezzani R, D'Amico A, Piva L, Leonardi E, Torella A, Soraru G, Palmieri A, Smaniotto G, Gavassini BF, Vianello A, Nigro V, Bertini E, Angelini C, Tosatto SC, Pegoraro E. Cardiomyopathy in patients with POMT1-related congenital and limb-girdle muscular dystrophy. Eur J Hum Genet. 2012 Dec;20(12):1234-9. doi: 10.1038/ejhg.2012.71. Epub 2012 May 2. (http://www.ncbi.nlm.nih.gov/pubmed/22549409?dopt=Abstract)
  • Kim DS, Hayashi YK, Matsumoto H, Ogawa M, Noguchi S, Murakami N, Sakuta R, Mochizuki M, Michele DE, Campbell KP, Nonaka I, Nishino I. POMT1 mutation results in defective glycosylation and loss of laminin-binding activity in alpha-DG. Neurology. 2004 Mar 23;62(6):1009-11. (http://www.ncbi.nlm.nih.gov/pubmed/15037715?dopt=Abstract)
  • Lommel M, Cirak S, Willer T, Hermann R, Uyanik G, van Bokhoven H, Körner C, Voit T, Barić I, Hehr U, Strahl S. Correlation of enzyme activity and clinical phenotype in POMT1-associated dystroglycanopathies. Neurology. 2010 Jan 12;74(2):157-64. doi: 10.1212/WNL.0b013e3181c919d6. (http://www.ncbi.nlm.nih.gov/pubmed/20065251?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/10585)
  • OMIM: PROTEIN O-MANNOSYLTRANSFERASE 1 (http://omim.org/entry/607423)

 

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: July 7, 2014