|http://ghr.nlm.nih.gov/ A service of the U.S. National Library of Medicine®|
The official name of this gene is “succinate dehydrogenase complex, subunit B, iron sulfur (Ip).”
SDHB is the gene's official symbol. The SDHB gene is also known by other names, listed below.
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, which are structures inside cells that convert the energy from food into a form that cells can use.
Within mitochondria, the SDH enzyme links two important pathways in energy conversion: the citric acid cycle (or Krebs cycle) and oxidative phosphorylation. As part of the citric acid cycle, the SDH enzyme converts a compound called succinate to another compound called fumarate. Negatively charged particles called electrons are released during this reaction. The SDHB protein provides an attachment site for electrons as they are transferred to the oxidative phosphorylation pathway. In oxidative phosphorylation, the electrons help create an electrical charge that provides energy for the production of adenosine triphosphate (ATP), the cell's main energy source.
Succinate, the compound on which the SDH enzyme acts, is an oxygen sensor in the cell and can help turn on specific pathways that stimulate cells to grow in a low-oxygen environment (hypoxia). In particular, succinate stabilizes a protein called hypoxia-inducible factor (HIF) by preventing a reaction that would allow HIF to be broken down. HIF controls several important genes involved in cell division and the formation of new blood vessels in a hypoxic environment.
The SDHB gene is a tumor suppressor, which means it prevents cells from growing and dividing in an uncontrolled way.
The SDHB gene belongs to a family of genes called mitochondrial respiratory chain complex (mitochondrial respiratory chain complex genes).
A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.
More than 150 mutations in the SDHB gene have been identified in people with hereditary paraganglioma-pheochromocytoma type 4. People with this condition have paragangliomas, pheochromocytomas, or both. Paragangliomas and pheochromocytomas (a type of paraganglioma) are noncancerous tumors associated with the nervous system. An inherited SDHB gene mutation predisposes an individual to the condition, and a somatic mutation that deletes the normal copy of the gene is needed to cause hereditary paraganglioma-pheochromocytoma type 4.
Most of the inherited SDHB gene mutations change single protein building blocks (amino acids) in the SDHB protein sequence or result in a shortened protein. As a result, there is little or no SDH enzyme activity. Because the mutated SDH enzyme cannot convert succinate to fumarate, succinate accumulates in the cell. The excess succinate abnormally stabilizes HIF, which also builds up in cells. Excess HIF stimulates cells to divide and triggers the production of blood vessels when they are not needed. Rapid and uncontrolled cell division, along with the formation of new blood vessels, can lead to the development of tumors in people with hereditary paraganglioma-pheochromocytoma.
Mutations in the SDHB gene are found in some cases of nonsyndromic paraganglioma or pheochromocytoma, which are non-hereditary forms of the condition. Most of these mutations change single amino acids in the SDHB protein. As in hereditary paraganglioma-pheochromocytoma type 4, these mutations are expected to decrease SDH enzyme activity, which stabilizes the HIF protein, causing it to build up in cells. Excess HIF protein abnormally stimulates cell division and the formation of blood vessels, which can lead to tumor formation.
At least 10 variants in the SDHB gene have been identified in people with Cowden syndrome or a similar disorder called Cowden-like syndrome. These conditions are characterized by multiple tumor-like growths called hamartomas and an increased risk of developing certain cancers, particularly breast cancer, thyroid cancer, and cancer of the uterine lining (endometrial cancer).
The SDHB gene variants associated with Cowden syndrome and Cowden-like syndrome change single amino acids in the SDHB protein, which likely alters the function of the SDH enzyme. Studies suggest that the defective enzyme could allow cells to grow and divide unchecked, leading to the formation of hamartomas and cancerous tumors. However, researchers are uncertain whether the identified SDHB gene variants are directly associated with Cowden syndrome and Cowden-like syndrome. Some of the variants described above have rarely been found in people without the features of these conditions.
The SDHB gene is involved in several cancers. Mutations in the SDHB gene have been found in a small number of people with gastrointestinal stromal tumors (GISTs), which are a type of tumor that occurs in the gastrointestinal tract, or renal cell carcinoma, which is a type of kidney cancer. SDHB gene mutations have been identified in people a condition called Carney-Stratakis syndrome in which affected individuals have both paraganglioma and GIST or in people with both renal cell cancer and paraganglioma. An inherited SDHB gene mutation predisposes an individual to cancer formation. An additional mutation that deletes the normal copy of the gene is needed to cause these forms of GIST, renal cell cancer, and paraganglioma. This second mutation, called a somatic mutation, is acquired during a person's lifetime and is present only in tumor cells.
Mutations of the SDHB gene lead to a reduction in the amount of SDHB protein in the cell and loss of SDH enzyme activity. Furthermore, even without a SDHB gene mutation, a subset of gastrointestinal stromal tumors have reduced SDHB protein and loss of SDH enzyme activity. Lack of SDH enzyme activity results in abnormal hypoxia signaling and formation of tumors.
Cytogenetic Location: 1p36.1-p35
Molecular Location on chromosome 1: base pairs 17,345,216 to 17,380,664
The SDHB gene is located on the short (p) arm of chromosome 1 between positions 36.1 and 35.
More precisely, the SDHB gene is located from base pair 17,345,216 to base pair 17,380,664 on chromosome 1.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about SDHB helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
acids ; adenosine triphosphate ; ATP ; cancer ; carcinoma ; cell ; cell division ; charged particles ; compound ; dehydrogenase ; endometrial ; enzyme ; gastrointestinal ; gene ; iron ; kidney ; mitochondria ; mutation ; nervous system ; oxidative phosphorylation ; oxygen ; pheochromocytoma ; phosphorylation ; protein ; protein sequence ; renal ; somatic mutation ; subunit ; syndrome ; thyroid ; tumor ; ubiquinone
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).
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? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.