RRM2B gene
The RRM2B gene provides instructions for a protein subunit that helps produce DNA building blocks, particularly within mitochondria.
Normal Function
The RRM2B gene provides instructions for making one piece, called the p53 inducible small subunit (p53R2), of a protein called ribonucleotide reductase (RNR). Two copies of the p53R2 subunit attach to two copies of another protein called R1 to form RNR. RNR helps produce DNA building blocks (nucleotides), which are joined to one another to form DNA.
RNRs containing p53R2 make nucleotides used for the formation of DNA in specialized cell structures called mitochondria. Mitochondria are the energy-producing centers in cells, and the DNA in these structures (mtDNA) contains genes essential for energy production (oxidative phosphorylation). The production of nucleotides by p53R2 helps maintain a normal amount of mtDNA in cells.
Health Conditions Related to Genetic Changes
Progressive external ophthalmoplegia
At least 17 mutations in the RRM2B gene have been identified in people with progressive external ophthalmoplegia. This disorder weakens the muscles that control eye movement and causes the eyelids to droop (ptosis). Some affected individuals have additional signs and symptoms, such as weakness of other muscles, extreme tiredness (fatigue), hearing loss, and digestive problems.
These mutations lead to impaired RNR activity, resulting in large deletions of genetic material from mtDNA in muscle tissue. It has been suggested that eye muscles are commonly affected by mitochondrial defects because they are especially dependent on oxidative phosphorylation for energy.
RRM2B-related mitochondrial DNA depletion syndrome
More than a dozen mutations in the RRM2B gene can cause RRM2B-related mitochondrial DNA depletion syndrome (RRM2B-MDS), a severe condition that affects multiple body systems. It typically leads to brain dysfunction combined with muscle weakness (encephalomyopathy) and a problem with kidney function known as renal tubulopathy.
The mutations that cause this disorder occur in both copies of the RRM2B gene. They reduce the activity or amount of RNR, which impairs the production of mtDNA nucleotides. A shortage of these nucleotides leads to a reduction in the amount of mtDNA (mtDNA depletion) and impairs mitochondrial function in many different types of cells.
Other Names for This Gene
- MTDPS8A
- MTDPS8B
- p53-inducible ribonucleotide reductase small subunit 2 homolog
- p53-inducible ribonucleotide reductase small subunit 2 short form beta
- p53-inducible ribonucleotide reductase small subunit 2-like protein
- P53R2
- ribonucleoside-diphosphate reductase subunit M2 B isoform 1
- ribonucleoside-diphosphate reductase subunit M2 B isoform 2
- ribonucleoside-diphosphate reductase subunit M2 B isoform 3
- ribonucleotide reductase M2 B (TP53 inducible)
- TP53-inducible ribonucleotide reductase M2 B
