SDHA

succinate dehydrogenase complex flavoprotein subunit A

5 disorders 3 untyped 2 causative 5p15.33 gene with protein product

HGNC:10680 Monarch NCBI Gene 6389 ENSG00000073578 UniProt P31040 OMIM 600857

Previous symbols: SDH2. Aliases: FP, SDHF.

Normal function · from ai-gene-review (P31040, commit 79fe13b38970) · AI-generated, not KB evidence

SDHA encodes the flavoprotein (Fp) subunit of succinate dehydrogenase (SDH, Complex II), a heterotetrameric enzyme (SDHA/SDHB/SDHC/SDHD) embedded in the mitochondrial inner membrane. SDHA contains a covalently bound FAD cofactor (attached at His99) and catalyzes the oxidation of succinate to fumarate as part of the TCA cycle. The electrons from succinate oxidation are transferred via FAD to the iron-sulfur clusters in SDHB and ultimately to ubiquinone bound at the SDHC/SDHD membrane interface, coupling the TCA cycle to the electron transport chain. Complex II is unique among OXPHOS complexes in that it does NOT pump protons across the inner membrane. SDHA also functions as a tumor suppressor; loss-of-function mutations cause paraganglioma/pheochromocytoma (PPGL5) via succinate accumulation and pseudohypoxic HIF1a stabilization. Biallelic mutations cause Leigh syndrome, mitochondrial complex II deficiency, and dilated cardiomyopathy.

SDHA is the catalytic flavoprotein subunit of succinate dehydrogenase (Complex II). It contains a covalently bound FAD cofactor at His99 and catalyzes the oxidation of succinate to fumarate as part of the TCA cycle (GO:0006099). The electrons are transferred via FAD through SDHB iron-sulfur centers to ubiquinone, coupling the TCA cycle to the electron transport chain (GO:0006121). SDHA enables succinate dehydrogenase activity (GO:0000104) and contributes to the overall succinate dehydrogenase quinone activity (GO:0008177) of the Complex II heterotetramer. The complex resides in the inner mitochondrial membrane with SDHA facing the matrix.

molecular function: succinate dehydrogenase activity · contributes to molecular function: succinate dehydrogenase (quinone) activity · directly involved in: mitochondrial electron transport, succinate to ubiquinone; tricarboxylic acid cycle · locations: mitochondrial matrix · in complex: respiratory chain complex II (succinate dehydrogenase)

In the knowledge base · computed from kb/ at build time

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.

Disorder	Relationship	Where the gene appears
Hereditary Pheochromocytoma-Paraganglioma Syndrome	causative
SDHA-Related Neurodegeneration With Ataxia and Optic Atrophy	causative	mechanism: Catalytically Inert SDHA Subunit Competing for Complex II Assembly; Divergence From the SDHx Tumour-Predisposition Arm; Failure of Covalent FAD Attachment to the SDHA Flavoprotein; Heterozygous SDHA Missense Allele at a Conserved Arginine variant: NM_004168.4(SDHA):c.1351C>T (p.Arg451Cys); NM_004168.4(SDHA):c.1984C>T (p.Arg662Cys) animal model: Saccharomyces cerevisiae
Dilated Cardiomyopathy 1GG	untyped germline partial loss of function	mechanism: SDHA p.Gly555Glu Homozygosity
Mitochondrial Complex II Deficiency, Nuclear Type 1	untyped	mechanism: SDHA Loss and Complex II (Succinate Dehydrogenase) Deficiency
Pheochromocytoma and Paraganglioma	untyped Germline Loss-of-Function Mutations	mechanism: Succinate Dehydrogenase Complex Dysfunction subtype: PGL5

ClinGen gene–disease validity · snapshot 2026-10-03 · matched to entries by MONDO

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.

ClinGen disease	MOI	Classification	dismech entry
Leigh syndrome MONDO:0009723	AR	Moderate 2019-05-20	Leber-like Hereditary Optic Neuropathy, Autosomal Recessive 1 not named Leigh Syndrome not named
hereditary pheochromocytoma-paraganglioma MONDO:0017366	AD	Definitive 2021-06-17	Hereditary Pheochromocytoma-Paraganglioma Syndrome causative
mitochondrial disease MONDO:0044970	AD	Limited 2025-08-11	no dismech entry
mitochondrial disease MONDO:0044970	AR	Definitive 2024-10-17	no dismech entry

Mechanism modules · computed from kb/

oncometabolite_dioxygenase_inhibition via Pheochromocytoma and Paraganglioma

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.