MMACHC - methylmalonic aciduria (cobalamin deficiency) cblC type, with homocystinuria - Genetics Home Reference

MMACHC - methylmalonic aciduria (cobalamin deficiency) cblC type, with homocystinuria - Genetics Home Reference

MMACHC

On this page:

 

• Name 
• Normal function 
• Genetic changes 
• Gene location 
• Additional information
• Other names 
• About genes 
• Glossary definitions

What is the official name of the MMACHC gene?

The official name of this gene is “methylmalonic aciduria (cobalamin deficiency) cblC type, with homocystinuria.”

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

Read more about gene names and symbols on the About page.

What is the normal function of the MMACHC gene?

The MMACHC gene provides instructions for making a protein that helps convert vitamin B12 (also called cobalamin) into one of two molecules, adenosylcobalamin (AdoCbl) or methylcobalamin (MeCbl). AdoCbl is required for the normal function of an enzyme known as methylmalonyl CoA mutase. This enzyme helps break down certain protein building blocks (amino acids), fats (lipids), and cholesterol. AdoCbl is called a cofactor because it helps methylmalonyl CoA mutase carry out its function. MeCbl is also a cofactor, but for an enzyme known as methionine synthase. This enzyme converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds.

Research indicates that the MMACHC protein plays a role in processing different forms of vitamin B12 so that they can be converted to either of the cofactors, AdoCbl or MeCbl. MMACHC also interacts with another protein called MMADHC (produced from the MMADHC gene). Together these proteins transport the processed vitamin B12 to regions of the cell in which each cofactor is needed: specialized structures that serve as energy-producing centers (the mitochondria), where AdoCbl functions, or the fluid inside the cell (the cytoplasm), where MeCbl functions. Additional chemical reactions then convert vitamin B12 into AdoCbl or MeCbl.

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

methylmalonic acidemia with homocystinuria - caused by mutations in the MMACHC gene

Dozens of MMACHC gene mutations have been found to cause methylmalonic acidemia with homocystinuria, cblC type, the most common form of a disorder that causes developmental delay, eye defects, neurological problems, and blood abnormalities. The most common mutation involved in this condition, called 271dupA, inserts an extra DNA building block (nucleotide) at position 271 of the gene. This change alters the protein blueprint, leading to production of an abnormally short protein that is unable to function. Other MMACHC gene mutations also lead to production of a protein with impaired function. A shortage of functional MMACHC protein prevents normal processing and transport of vitamin B12, impairing production of both AdoCbl and MeCbl. Because both of these cofactors are missing, the enzymes that require them (methylmalonyl CoA mutase and methionine synthase) do not function normally. As a result, certain amino acids, lipids, and cholesterol are not broken down and homocysteine cannot be converted to methionine. This dual defect results in a buildup of toxic compounds as well as homocysteine, and a decrease in the production of methionine within the body. This combination of imbalances leads to the signs and symptoms of methylmalonic acidemia with homocystinuria.

Where is the MMACHC gene located?

Cytogenetic Location: 1p34.1

Molecular Location on chromosome 1: base pairs 45,500,184 to 45,511,067

(Homo sapiens Annotation Release 107, GRCh38.p2) (NCBI)

The MMACHC gene is located on the short (p) arm of chromosome 1 at position 34.1.

More precisely, the MMACHC gene is located from base pair 45,500,184 to base pair 45,511,067 on chromosome 1.

See How do geneticists indicate the location of a gene? in the Handbook.

Where can I find additional information about MMACHC?

You and your healthcare professional may find the following resources about MMACHC helpful.

• Gene Reviews - Clinical summary
• Genetic Testing Registry - Repository of genetic test information (1 link)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

• PubMed - Recent literature
• OMIM - Genetic disorder catalog
• Research Resources - Tools for researchers (3 links)

What other names do people use for the MMACHC gene or gene products?

• cblC
• DKFZP564I122
• methylmalonic aciduria and homocystinuria type C protein

See How are genetic conditions and genes named? in the Handbook.

Where can I find general information about genes?

The Handbook provides basic information about genetics in clear language.

• What is DNA?
• What is a gene?
• How do genes direct the production of proteins?
• How can gene mutations affect health and development?

These links provide additional genetics resources that may be useful.

• Genetics Education
• Human Genome Project
• Resources for Genetics Researchers

What glossary definitions help with understanding MMACHC?

acids ; aciduria ; amino acid ; cell ; cholesterol ; CoA ; cobalamin ; cofactor ; cytoplasm ; deficiency ;developmental delay ; DNA ; enzyme ; gene ; methionine ; mitochondria ; mutation ; neurological ;nucleotide ; protein ; toxic ; vitamin B12

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.

See also Understanding Medical Terminology.

References (7 links)

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? in the Handbook