SDHB

succinate dehydrogenase complex iron sulfur subunit B

4 disorders 2 untyped 1 susceptibility 1 causative 1p36.13 gene with protein product

HGNC:10681 Monarch NCBI Gene 6390 ENSG00000117118 UniProt P21912 OMIM 185470

Previous symbols: SDH1, SDH.

Normal function · from ai-gene-review (P21912, commit 79fe13b38970) · AI-generated, not KB evidence

SDHB encodes the iron-sulfur protein (Ip) subunit of succinate dehydrogenase (SDH, Complex II), a heterotetrameric enzyme (SDHA/SDHB/SDHC/SDHD) embedded in the mitochondrial inner membrane. SDHB contains three iron-sulfur clusters ([2Fe-2S], [4Fe-4S], [3Fe-4S]) organized in a butterfly-like two-domain structure that relays electrons from the FAD cofactor in SDHA to ubiquinone bound at the SDHC/SDHD membrane interface. SDHB also directly contacts the ubiquinone binding site via residues Pro197, Trp201, and Ile246. Complex II is unique among OXPHOS complexes in that it does NOT pump protons across the inner membrane. SDHB functions as a tumor suppressor; heterozygous loss-of-function mutations cause paraganglioma/ pheochromocytoma (PPGL4) via succinate accumulation and pseudohypoxic HIF stabilization. Biallelic mutations cause mitochondrial complex II deficiency type 4 (MC2DN4) with leukoencephalopathy.

SDHB is the iron-sulfur protein (Ip) subunit of succinate dehydrogenase (Complex II). It contains three iron-sulfur clusters ([2Fe-2S], [4Fe-4S], [3Fe-4S]) organized in a butterfly-like two-domain structure that relays electrons from the FAD cofactor in SDHA to ubiquinone at the SDHC/SDHD membrane interface. The primary subunit-specific molecular function of SDHB is electron transfer activity (GO:0009055), while it contributes to the overall succinate dehydrogenase (quinone) activity (GO:0008177) of the Complex II heterotetramer. SDHB also directly contacts the ubiquinone binding site via residues Pro197, Trp201, and Ile246 (GO:0048039 ubiquinone binding). The complex resides in the inner mitochondrial membrane with SDHB facing the matrix. SDHB is essential for coupling the TCA cycle (succinate oxidation) to the electron transport chain (ubiquinone reduction), the defining biological process GO:0006121.

molecular function: electron transfer 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
Cowden Syndrome	susceptibility	mechanism: Reduced Succinate Dehydrogenase Activity subtype: CS2 scoped to subtype: CS2
Hereditary Pheochromocytoma-Paraganglioma Syndrome	causative germlinegermline and somatic loss of function	mechanism: Biallelic SDHx Loss and Succinate Dehydrogenase Deficiency; Germline SDHx First-Hit Inactivation
Carney-Stratakis syndrome	untyped Germline Loss-of-Function Variants	mechanism: Germline SDH complex loss of function
Pheochromocytoma and Paraganglioma	untyped Germline Loss-of-Function Mutations	mechanism: Succinate Dehydrogenase Complex Dysfunction subtype: PGL4

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
hereditary pheochromocytoma-paraganglioma MONDO:0017366	AD	Definitive 2021-06-17	Hereditary Pheochromocytoma-Paraganglioma Syndrome causative
mitochondrial disease MONDO:0044970	AR	Definitive 2022-03-07	no dismech entry

Mechanism modules · computed from kb/

germline_two_hit_tumor_predisposition via Hereditary Pheochromocytoma-Paraganglioma Syndrome
oncometabolite_dioxygenase_inhibition via Pheochromocytoma and Paraganglioma

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