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Genetics Home Reference: your guide to understanding genetic conditions
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MMAA

Reviewed July 2011

What is the official name of the MMAA gene?

The official name of this gene is “methylmalonic aciduria (cobalamin deficiency) cblA type.”

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

What is the normal function of the MMAA gene?

The MMAA gene provides instructions for making a protein that is involved in the formation of a compound called adenosylcobalamin (AdoCbl). AdoCbl, which is derived from vitamin B12 (also called cobalamin), is necessary for the normal function of an enzyme known as methylmalonyl CoA mutase. This enzyme helps break down certain proteins, fats (lipids), and cholesterol.

Research indicates that the MMAA protein may play a role in one of the last steps in AdoCbl formation, the transport of vitamin B12 into mitochondria (specialized structures inside cells that serve as energy-producing centers). Additional chemical reactions then convert vitamin B12 into AdoCbl. Other studies suggest that the MMAA protein may help stabilize methylmalonyl CoA mutase and protect the enzyme from being turned off (inactivated).

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

methylmalonic acidemia - caused by mutations in the MMAA gene

More than 25 mutations in the MMAA gene have been found to cause methylmalonic acidemia, a condition characterized by feeding difficulties, developmental delay, and long term health problems. Some of these mutations add, delete, or duplicate a small amount of genetic material in the gene. Other mutations change a single protein building block (amino acid) used to make the MMAA protein. These mutations can lead to the production of an unstable MMAA protein or an abnormally small, nonfunctional version of the protein. It is unclear how the abnormal MMAA protein leads to the serious medical problems associated with methylmalonic acidemia. Studies suggest that without the activity of this protein, AdoCbl may not be made properly. A lack of AdoCbl impairs the function of methylmalonyl CoA mutase, which results in the incomplete break down of certain proteins and lipids. This defect allows toxic compounds to build up in the body's organs and tissues. Research suggests that a lack of AdoCbl leading to impaired methylmalonyl CoA mutase function causes the signs and symptoms of methylmalonic acidemia.

Where is the MMAA gene located?

Cytogenetic Location: 4q31.21

Molecular Location on chromosome 4: base pairs 145,619,387 to 145,660,034

The MMAA gene is located on the long (q) arm of chromosome 4 at position 31.21.

The MMAA gene is located on the long (q) arm of chromosome 4 at position 31.21.

More precisely, the MMAA gene is located from base pair 145,619,387 to base pair 145,660,034 on chromosome 4.

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 MMAA?

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

  • cblA
  • methylmalonic aciduria (cobalamin deficiency) type A
  • methylmalonic aciduria type A
  • MMAA_HUMAN

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 MMAA?

aciduria ; amino acid ; cholesterol ; CoA ; cobalamin ; cofactor ; compound ; deficiency ; developmental delay ; enzyme ; gene ; mitochondria ; protein ; toxic ; vitamin B12

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

References

  • Chandler RJ, Venditti CP. Genetic and genomic systems to study methylmalonic acidemia. Mol Genet Metab. 2005 Sep-Oct;86(1-2):34-43. Epub 2005 Sep 22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16182581?dopt=Abstract)
  • Dobson CM, Wai T, Leclerc D, Wilson A, Wu X, Doré C, Hudson T, Rosenblatt DS, Gravel RA. Identification of the gene responsible for the cblA complementation group of vitamin B12-responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements. Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15554-9. Epub 2002 Nov 15. (http://www.ncbi.nlm.nih.gov/pubmed/12438653?dopt=Abstract)
  • Froese DS, Kochan G, Muniz JR, Wu X, Gileadi C, Ugochukwu E, Krysztofinska E, Gravel RA, Oppermann U, Yue WW. Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation. J Biol Chem. 2010 Dec 3;285(49):38204-13. doi: 10.1074/jbc.M110.177717. Epub 2010 Sep 28. (http://www.ncbi.nlm.nih.gov/pubmed/20876572?dopt=Abstract)
  • Gene Review: Methylmalonic Acidemia (http://www.ncbi.nlm.nih.gov/books/NBK1231)
  • Hörster F, Baumgartner MR, Viardot C, Suormala T, Burgard P, Fowler B, Hoffmann GF, Garbade SF, Kölker S, Baumgartner ER. Long-term outcome in methylmalonic acidurias is influenced by the underlying defect (mut0, mut-, cblA, cblB). Pediatr Res. 2007 Aug;62(2):225-30. (http://www.ncbi.nlm.nih.gov/pubmed/17597648?dopt=Abstract)
  • Korotkova N, Lidstrom ME. MeaB is a component of the methylmalonyl-CoA mutase complex required for protection of the enzyme from inactivation. J Biol Chem. 2004 Apr 2;279(14):13652-8. Epub 2004 Jan 20. (http://www.ncbi.nlm.nih.gov/pubmed/14734568?dopt=Abstract)
  • Lerner-Ellis JP, Dobson CM, Wai T, Watkins D, Tirone JC, Leclerc D, Doré C, Lepage P, Gravel RA, Rosenblatt DS. Mutations in the MMAA gene in patients with the cblA disorder of vitamin B12 metabolism. Hum Mutat. 2004 Dec;24(6):509-16. Erratum in: Hum Mutat. 2005 Mar;25(3):317. (http://www.ncbi.nlm.nih.gov/pubmed/15523652?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/166785)
  • Yang X, Sakamoto O, Matsubara Y, Kure S, Suzuki Y, Aoki Y, Suzuki Y, Sakura N, Takayanagi M, Iinuma K, Ohura T. Mutation analysis of the MMAA and MMAB genes in Japanese patients with vitamin B(12)-responsive methylmalonic acidemia: identification of a prevalent MMAA mutation. Mol Genet Metab. 2004 Aug;82(4):329-33. (http://www.ncbi.nlm.nih.gov/pubmed/15308131?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: July 2011
Published: February 23, 2015