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Function

Iron-sulfur protein (IP) subunit of the succinate dehydrogenase complex (mitochondrial respiratory chain complex II), responsible for transferring electrons from succinate to ubiquinone (coenzyme Q) (PubMed:26925370, PubMed:27604842). SDH also oxidizes malate to the non-canonical enol form of oxaloacetate, enol-oxaloacetate (By similarity). Enol-oxaloacetate, which is a potent inhibitor of the succinate dehydrogenase activity, is further isomerized into keto-oxaloacetate (By similarity).

Involvement in disease

Pheochromocytoma/paraganglioma syndrome 4

PPGL4

A form of pheochromocytoma/paraganglioma syndrome, a tumor predisposition syndrome characterized by the development of neuroendocrine tumors, usually in adulthood. Pheochromocytomas are catecholamine-producing tumors that arise from chromaffin cells in the adrenal medulla. Paragangliomas develop from sympathetic paraganglia in the thorax, abdomen, and pelvis, as well as from parasympathetic paraganglia in the head and neck. PPGL4 inheritance is autosomal dominant.

None

The disease is caused by variants affecting the gene represented in this entry.

Paraganglioma and gastric stromal sarcoma

PGGSS

Gastrointestinal stromal tumors may be sporadic or inherited in an autosomal dominant manner, alone or as a component of a syndrome associated with other tumors, such as in the context of neurofibromatosis type 1 (NF1). Patients have both gastrointestinal stromal tumors and paragangliomas. Susceptibility to the tumors was inherited in an apparently autosomal dominant manner, with incomplete penetrance.

None

The disease is caused by variants affecting the gene represented in this entry.

Mitochondrial complex II deficiency, nuclear type 4

MC2DN4

A form of mitochondrial complex II deficiency, a disorder with heterogeneous clinical manifestations. Some patients have multisystem involvement of the brain, heart, muscle, liver, and kidneys resulting in death in infancy, whereas others have only isolated cardiac or muscle involvement with onset in adulthood and normal cognition. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome. MC2DN4 is a severe, autosomal recessive form characterized by early-onset progressive neurodegeneration with leukoencephalopathy.

None

The disease is caused by variants affecting the gene represented in this entry.

Pathway

Carbohydrate metabolism; tricarboxylic acid cycle; fumarate from succinate (eukaryal route): step 1/1.

Sequence similarities

Belongs to the succinate dehydrogenase/fumarate reductase iron-sulfur protein family.

Cellular localization

  • Mitochondrion inner membrane
  • Peripheral membrane protein
  • Matrix side

Alternative names

SDH, SDH1, SDHB, Iron-sulfur subunit of complex II, Malate dehydrogenase [quinone] iron-sulfur subunit, Ip

Target type

Proteins

Primary research area

Cardiovascular

Molecular weight

31630Da

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