SDHD
Overview
SDHD (Succinate Dehydrogenase Complex Subunit D) encodes a membrane-anchoring subunit of mitochondrial complex II. Germline mutations in SDHD are a well-established cause of hereditary paraganglioma-pheochromocytoma syndrome, with tumors arising via the pseudohypoxia signaling axis. In the TCGA PCC/PGL cohort, SDHD germline mutations are among the eight canonical susceptibility genes.
Alterations observed in the corpus
- Germline pathogenic mutations identified in the TCGA PCC/PGL cohort (pcpg_tcga_pub, n=173); specific to the pseudohypoxia mRNA subtype alongside SDHB, VHL, and somatic VHL/EPAS1 mutations. Germline rate listed among the ≤2% each tier. PMID:28162975
- SDHD germline mutations were mutually exclusive with other major driver gene events (p < 1e-4). PMID:28162975
Cancer types (linked)
- PHC / PGNG: SDHD germline defines pseudohypoxia subtype tumors; co-occurring alterations include genome-doubling and hypermethylation. PMID:28162975
Co-occurrence and mutual exclusivity
Therapeutic relevance
- As an SDH-complex member, SDHD-mutant tumors are expected to accumulate succinate/glutamine; glutaminase inhibitors proposed as a therapeutic avenue by the authors. PMID:28162975
Open questions
- Functional distinction between SDHB and SDHD germline tumors within the pseudohypoxia subtype (e.g., differential risk of metastasis) was not fully resolved in the corpus. PMID:28162975
Sources
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