SDHA gene
The SDHA gene provides instructions for a subunit of the succinate dehydrogenase enzyme, which is vital for cellular energy production and acts as a tumor suppressor.
Normal Function
The SDHA gene provides instructions for making one of four subunits of the succinate dehydrogenase (SDH) enzyme. This enzyme is located in the mitochondria and links the citric acid cycle (Krebs cycle) to oxidative phosphorylation, the process that produces adenosine triphosphate (ATP), the cell's main energy source.
The SDHA protein is the active subunit that converts succinate to fumarate. Succinate also acts as an oxygen sensor; it stabilizes a protein called hypoxia-inducible factor (HIF). HIF controls genes involved in cell division and blood vessel formation. Because the SDHA gene prevents uncontrolled cell growth, it is classified as a tumor suppressor gene.
Health Conditions Related to Genetic Changes
Gastrointestinal stromal tumor
Mutations in the SDHA gene can cause SDH-deficient gastrointestinal stromal tumor (GIST). These tumors typically occur in the stomach during childhood or early adulthood.
- Inherited germline mutations increase risk, but a second somatic mutation is usually required for tumor formation.
- Lack of functional SDHA protein leads to a buildup of succinate.
- Excess succinate stabilizes HIF, which triggers uncontrolled cell division and the formation of unnecessary blood vessels.
- SDHA mutations are associated with Carney triad (GIST, pulmonary chondroma, and paraganglioma) and Carney-Stratakis syndrome (GIST and paraganglioma).
Nonsyndromic paraganglioma
Mutations in the SDHA gene are identified in people with nonsyndromic paraganglioma or pheochromocytoma, which are noncancerous tumors of the nervous system.
- These mutations change single amino acids or result in a shortened protein, leading to loss of SDH enzyme activity.
- Similar to GIST, the resulting accumulation of succinate stabilizes HIF, promoting tumor growth through increased cell division and blood vessel formation.
Leigh syndrome
SDHA gene mutations have been identified in a small number of people with Leigh syndrome, a progressive brain disorder appearing in infancy or early childhood.
- Symptoms include vomiting, seizures, delayed development, muscle weakness, and movement problems.
- These mutations disrupt SDH enzyme activity, impairing mitochondrial energy production.
- The exact mechanism linking these mutations to the specific features of Leigh syndrome is not fully understood.
Other Names for This Gene
- CMD1GG
- DHSA_HUMAN
- flavoprotein subunit of complex II
- FP
- SDH1
- SDH2
- SDHF
- succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial
- succinate dehydrogenase complex flavoprotein subunit
- succinate dehydrogenase complex subunit A, flavoprotein (Fp)
- succinate dehydrogenase complex, subunit A, flavoprotein (Fp)