SDHB
Chr 1ADIsolated casesARsuccinate dehydrogenase complex iron sulfur subunit B
Also known as: CWS2, IP, MC2DN4, PGL4, PPGL4, SDH, SDH1, SDH2
The protein functions as the iron-sulfur subunit of succinate dehydrogenase complex II, converting succinate to fumarate in the citric acid cycle and transferring electrons to the oxidative phosphorylation pathway. Mutations cause autosomal dominant pheochromocytoma/paraganglioma syndrome 4, gastrointestinal stromal tumors, and autosomal recessive mitochondrial complex II deficiency. The pathogenic mechanism involves loss of tumor suppressor function, leading to mitochondrial dysfunction and disrupted oxygen sensing through HIF1 transcription factor stabilization.
Definitive — sufficient evidence for diagnostic panels
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SDHB · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools