SDHD (O14521) variants and mutations

SDHD (also known as O14521) is a human protein-coding gene encoding a succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial protein. It provides a membrane-anchoring component of succinate dehydrogenase and is required for normal complex II electron transfer. Germline loss-of-function variants, often showing a parent-of-origin effect, strongly predispose to head-and-neck paragangliomas and pheochromocytomas. This analysis covers 517 SDHD variants and mutations. Of these, 79% have computational variant effect predictions. Disease context includes pheochromocytoma/paraganglioma syndrome 1, hereditary pheochromocytoma-paraganglioma, and paragangliomas with sensorineural hearing loss. Example SDHD variants include M1I, M1L, and M1T.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable SDHD variants

Examples include M1I, M1L, M1T, M1V, A2E, A2G, A2T, A2V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.