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

SDHC gene

The SDHC gene encodes a subunit of the succinate dehydrogenase enzyme that anchors it to the mitochondrial membrane, playing a vital role in energy metabolism and tumor suppression.

Normal Function

The SDHC gene provides instructions for making a subunit of the succinate dehydrogenase (SDH) enzyme. The SDHC protein is responsible for anchoring the SDH enzyme within the mitochondrial membrane.

The SDH enzyme is essential for linking the citric acid cycle and oxidative phosphorylation. By converting succinate to fumarate, the enzyme releases electrons that are transferred through the SDHC protein to the oxidative phosphorylation pathway, facilitating the production of adenosine triphosphate (ATP).

Additionally, the SDH enzyme helps regulate the stability of hypoxia-inducible factor (HIF) by managing levels of succinate. Because the SDHC gene acts as a tumor suppressor, it is critical for preventing uncontrolled cell growth and division.

Health Conditions Related to Genetic Changes

Gastrointestinal stromal tumor

Changes in the SDHC gene can lead to SDH-deficient GIST. These tumors are often associated with promoter hypermethylation (an epimutation), where extra methyl groups attach to the gene's promoter region, reducing gene expression. Other cases are caused by germline mutations.

Tumor formation typically requires a second genetic change that affects the normal copy of the gene. The resulting loss of functional SDHC protein leads to a buildup of succinate, which stabilizes HIF and promotes tumor growth. These tumors are sometimes associated with:

  • Carney triad: GIST, paraganglioma, and pulmonary chondroma.
  • Carney-Stratakis syndrome: GIST and paraganglioma.
  • Incomplete Carney triad: GIST and pulmonary chondroma.

Hereditary paraganglioma-pheochromocytoma

More than 30 mutations in the SDHC gene are linked to hereditary paraganglioma-pheochromocytoma type 3. This condition predisposes individuals to develop paragangliomas and pheochromocytomas. An inherited germline mutation combined with a somatic deletion of the normal gene copy leads to reduced SDH activity, HIF accumulation, and tumor development.

Frequently Asked Questions

germline mutation is a genetic change present in every cell of the body from conception, which is inherited and increases the lifetime risk of developing tumors. In contrast, promoter hypermethylation is an epimutation where chemical groups attach to the SDHC gene's DNA, silencing its expression without changing the underlying genetic code. In SDHC-related GISTs, promoter hypermethylation is a common cause of gene silencing, particularly in sporadic cases, whereas germline mutations are more typical in hereditary syndromes like hereditary paraganglioma-pheochromocytoma type 3.
The SDHC protein serves as the anchor that attaches the succinate dehydrogenase enzyme complex to the inner mitochondrial membrane. This physical positioning is crucial because it allows the enzyme to efficiently transfer electrons from the citric acid cycle directly into the electron transport chain. Without proper anchoring by SDHC, the link between the Krebs cycle and oxidative phosphorylation is disrupted, impairing the cell's ability to generate ATP, the primary energy currency, and altering metabolic signaling pathways that regulate cell growth.
Tumors associated with SDHC mutations, such as paragangliomas and pheochromocytomas, are more frequently benign compared to those associated with SDHB mutations. However, they are not without risk; some can still become malignant or cause significant health issues due to hormone secretion. GISTs associated with SDHC can also be malignant, but the overall prognosis is often better than for SDHB-associated GISTs, which have a higher propensity for metastasis.
Early signs often relate to the location of the tumor. Head and neck paragangliomas may present with a visible or palpable neck mass, hearing loss, or tinnitus. Pheochromocytomas in the adrenal glands may cause episodic headaches, sweating, rapid heart rate, and high blood pressure. Because these symptoms can be intermittent and mild, regular screening with blood or urine tests for catecholamines and imaging studies is essential for individuals with a known SDHC mutation.
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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