SDHC

Chr 1ADIsolated cases

succinate dehydrogenase complex subunit C

Also known as: CYB560, CYBL, PGL3, PPGL3, QPS1, SDH3

NCBI Gene: 6391 ENSG00000143252 UniProt: Q99643 OMIM: 602413

SDHC encodes an integral membrane subunit of succinate dehydrogenase (mitochondrial complex II) that anchors the catalytic core to the inner mitochondrial membrane, functioning as a key enzyme in both the tricarboxylic acid cycle and aerobic respiration. Mutations cause autosomal dominant paraganglioma and pheochromocytoma syndrome 3, as well as gastrointestinal stromal tumors, through a dominant negative mechanism. The condition can also occur as isolated cases without family history.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes one of four nuclear-encoded subunits that comprise succinate dehydrogenase, also known as mitochondrial complex II, a key enzyme complex of the tricarboxylic acid cycle and aerobic respiratory chains of mitochondria. The encoded protein is one of two integral membrane proteins that anchor other subunits of the complex, which form the catalytic core, to the inner mitochondrial membrane. There are several related pseudogenes for this gene on different chromosomes. Mutations in this gene have been associated with paragangliomas. Alternatively spliced transcript variants have been described. [provided by RefSeq, May 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Gastrointestinal stromal tumorMIM #606764

ADIsolated cases

Paraganglioma and gastric stromal sarcomaMIM #606864

Pheochromocytoma/paraganglioma syndrome 3MIM #605373

Clinical highlights

Gene-disease validity (ClinGen)

hereditary pheochromocytoma-paraganglioma · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.26

LOEUF

LOF*

Mechanism· G2P

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GeneReview available — SDHC