Mitochondrial complex 2 deficiency, nuclear type 3: genes and variants

Genes linked to Mitochondrial complex 2 deficiency, nuclear type 3

• SDHB: Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial

  It transfers electrons from succinate oxidation through iron-sulfur centers toward ubiquinone in mitochondrial complex II. Heterozygous loss-of-function variants strongly predispose to paraganglioma and pheochromocytoma and can also increase renal-tumor and gastrointestinal-stromal-tumor risk.

  7 disease-causing and 12 uncertain variants in SDHB are linked to Mitochondrial complex 2 deficiency, nuclear type 3.

• SDHD: Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial

  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.

  3 disease-causing and 21 uncertain variants in SDHD are linked to Mitochondrial complex 2 deficiency, nuclear type 3.

Where Mitochondrial complex 2 deficiency, nuclear type 3 variants cluster

• SDHB 4Fe-4S ferredoxin-type (positions 176–206): 3 of 7 disease-causing changes, 3.9× more than its size predicts.

Known disease-causing variants in Mitochondrial complex 2 deficiency, nuclear type 3

Same protein, different disease

• Gastrointestinal stromal tumor is also caused by SDHB variants; they fall partly in the same places as the Mitochondrial complex 2 deficiency, nuclear type 3 variants (53 disease-causing).
• Pheochromocytoma/paraganglioma syndrome 5 is also caused by SDHB variants; they fall partly in the same places as the Mitochondrial complex 2 deficiency, nuclear type 3 variants (48 disease-causing).
• Pheochromocytoma is also caused by SDHB variants; they fall partly in the same places as the Mitochondrial complex 2 deficiency, nuclear type 3 variants (47 disease-causing).
• Inherited phaeochromocytoma and paraganglioma excluding NF1 is also caused by SDHB variants; they fall mostly in different places as the Mitochondrial complex 2 deficiency, nuclear type 3 variants (4 disease-causing).
• Pheochromocytoma is also caused by SDHD variants; they fall partly in the same places as the Mitochondrial complex 2 deficiency, nuclear type 3 variants (14 disease-causing).
• Paragangliomas with sensorineural hearing loss is also caused by SDHD variants; they fall partly in the same places as the Mitochondrial complex 2 deficiency, nuclear type 3 variants (13 disease-causing).
• Carney-Stratakis syndrome is also caused by SDHD variants; they fall mostly in different places as the Mitochondrial complex 2 deficiency, nuclear type 3 variants (11 disease-causing).
• Cowden syndrome is also caused by SDHD variants; they fall partly in the same places as the Mitochondrial complex 2 deficiency, nuclear type 3 variants (11 disease-causing).
• Pheochromocytoma/paraganglioma syndrome 5 is also caused by SDHD variants; they fall mostly in different places as the Mitochondrial complex 2 deficiency, nuclear type 3 variants (4 disease-causing).

Diseases related to Mitochondrial complex 2 deficiency, nuclear type 3

• Pheochromocytoma/paraganglioma syndrome 5, also linked to SDHB and SDHD
• Pheochromocytoma, also linked to SDHB and SDHD
• Carney-Stratakis syndrome, also linked to SDHB and SDHD
• Hereditary pheochromocytoma and paraganglioma, also linked to SDHB and SDHD
• Gastrointestinal stromal tumor, also linked to SDHB
• Cowden syndrome, also linked to SDHD
• Mitochondrial complex II deficiency, nuclear type 1, also linked to SDHD
• Paragangliomas with sensorineural hearing loss, also linked to SDHD
• Inherited phaeochromocytoma and paraganglioma excluding NF1, also linked to SDHB

Frequently asked questions

Which genes are linked to Mitochondrial complex 2 deficiency, nuclear type 3?

In CATVariant, Mitochondrial complex 2 deficiency, nuclear type 3 is linked to 2 analyzed proteins: SDHB (Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial) and SDHD (Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial).

How many genetic variants are linked to Mitochondrial complex 2 deficiency, nuclear type 3?

55 variants: 10 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 33 are of uncertain significance or have conflicting reports.

Which uncertain variants in Mitochondrial complex 2 deficiency, nuclear type 3 look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.

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