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SDHB gene
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Gene

SDHB gene

The SDHB gene provides instructions for making a subunit of the succinate dehydrogenase enzyme, which is essential for cellular energy production and acts as a tumor suppressor.

Normal Function

The SDHB gene provides instructions for making one of four subunits of the succinate dehydrogenase (SDH) enzyme. The SDH enzyme plays a critical role in mitochondria, the structures inside cells that convert energy from food into a usable form.

Within mitochondria, the SDH enzyme links the citric acid cycle (Krebs cycle) and oxidative phosphorylation. During the citric acid cycle, the enzyme converts succinate to fumarate, releasing electrons. The SDHB protein provides an attachment site for these electrons as they are transferred to the oxidative phosphorylation pathway, where they help generate adenosine triphosphate (ATP), the cell's primary energy source.

Succinate also acts as an oxygen sensor. It stabilizes a protein called hypoxia-inducible factor (HIF) by preventing its breakdown. HIF regulates genes involved in cell division and blood vessel formation in low-oxygen (hypoxic) environments. As a tumor suppressor, the SDHB gene prevents cells from growing and dividing uncontrollably.

Health Conditions Related to Genetic Changes

Gastrointestinal stromal tumor

Mutations in the SDHB gene can lead to SDH-deficient GIST, a type of gastrointestinal stromal tumor. These tumors typically occur in the stomach during childhood or early adulthood. Individuals with this condition are at higher risk for:

  • Paragangliomas: Noncancerous tumors in the nervous system.
  • Pulmonary chondromas: Noncancerous lung tumors.

The combination of GIST and paraganglioma is known as Carney-Stratakis syndrome. The combination of GIST, paraganglioma, and pulmonary chondroma is known as Carney triad, while GIST and pulmonary chondroma is incomplete Carney triad.

Tumor formation requires both an inherited germline mutation and a secondary somatic mutation that deletes the normal copy of the gene. The resulting lack of functional SDHB protein causes succinate to build up, which abnormally stabilizes HIF, triggering uncontrolled cell division and unnecessary blood vessel formation.

Hereditary paraganglioma-pheochromocytoma

More than 150 mutations in the SDHB gene are associated with hereditary paraganglioma-pheochromocytoma type 4. This condition involves the development of paragangliomas and pheochromocytomas—noncancerous tumors associated with the nervous system. Similar to GIST, the reduction of SDH enzyme activity leads to the accumulation of HIF and subsequent tumor growth.

Nonsyndromic paraganglioma

SDHB mutations are also found in cases of nonsyndromic paraganglioma or pheochromocytoma, where there is no family history of these tumors. These mutations reduce SDH enzyme activity, leading to the same HIF-driven tumor formation process.

Other cancers

Mutations in the SDHB gene have been identified in a small number of people with renal cell carcinoma (kidney cancer), sometimes occurring alongside paraganglioma. These mutations lead to a reduction in SDHB protein and abnormal hypoxia signaling.

Frequently Asked Questions

Yes, SDHB-related conditions are inherited in an autosomal dominant pattern. This means that only one copy of the altered gene in each cell is sufficient to increase the risk of developing tumors. A parent with an SDHB mutation has a 50 percent chance of passing the genetic change to each of their children. Genetic counseling is recommended for affected individuals to discuss family planning and the option of predictive genetic testing for at-risk relatives.
Patients should seek emergency care if they experience sudden, severe headaches, palpitations, sweating, or high blood pressure, which may indicate a pheochromocytoma or paraganglioma releasing excess catecholamines. Additionally, any signs of gastrointestinal bleeding, such as black tarry stools or vomiting blood, require immediate attention as they may signal the presence or growth of a GIST. Regular monitoring is critical because these tumors can be asymptomatic until they reach a significant size or rupture.
Mutations in the SDHB gene carry the highest risk of malignant transformation among all succinate dehydrogenase subunits. While mutations in other SDH genes (like SDHD) often result in benign tumors, SDHB-associated tumors, particularly gastrointestinal stromal tumors (GISTs) and paragangliomas, have a significantly higher likelihood of becoming cancerous and metastasizing. This is why SDHB is considered the most aggressive of the SDH-related tumor suppressor genes.
The SDHB protein is part of the enzyme complex that converts succinate to fumarate. When SDHB function is lost, succinate accumulates within the cell. High levels of succinate stabilize hypoxia-inducible factor (HIF), a protein that normally breaks down in the presence of oxygen. Stabilized HIF tricks the cell into behaving as if it is in a low-oxygen environment, triggering pathways that promote cell division, blood vessel formation, and survival, thereby facilitating tumor growth and progression.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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