SDHAF2

SDHAF2 (also known as SDH5, PGL2, C11orf79) is a soluble mitochondrial-matrix assembly factor for succinate dehydrogenase (SDH), the respiratory chain Complex II that links the tricarboxylic acid cycle and the electron transport chain. SDHAF2 is not a subunit of the mature enzyme and has no succinate dehydrogenase catalytic activity of its own. Its defining role is to bind the flavoprotein subunit SDHA and, acting as a chaperone/assembly factor together with a dicarboxylate cofactor, to remodel and orient the flavin and capping domains of SDHA so that covalent attachment of the FAD cofactor (flavinylation) can occur. This covalent flavinylation is required for SDH assembly and activity. Germline loss-of-function mutations in SDHAF2 cause hereditary pheochromocytoma/paraganglioma (PPGL2); the G78R variant abolishes both SDHA binding and SDHA flavinylation.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

• oncometabolite_dioxygenase_inhibition via Pheochromocytoma and Paraganglioma