SDHD
Chr 11ARADsuccinate dehydrogenase complex subunit D
Also known as: CBT1, CII-4, CWS3, MC2DN3, PGL, PGL1, PPGL1, QPs3
The SDHD protein is a membrane-anchoring subunit of succinate dehydrogenase (complex II) that transfers electrons from succinate to ubiquinone in the mitochondrial electron transport chain. Mutations cause mitochondrial complex II deficiency (autosomal recessive inheritance) and pheochromocytoma/paraganglioma syndrome (autosomal dominant inheritance with paternal imprinting, meaning disease transmission occurs almost exclusively through the paternal allele). Loss of SDHD function leads to impaired cellular respiration and tumor formation through disrupted mitochondrial metabolism.
Limited evidence — not for standalone diagnostic reporting
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
SDHD · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools