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GENE:

SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)

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Other names: Succinate Dehydrogenase Complex Flavoprotein Subunit A, Flavoprotein Subunit Of Complex II, SDHF, Succinate Dehydrogenase [Ubiquinone] Flavoprotein Subunit, Mitochondrial, Succinate Dehydrogenase Complex, Subunit A, Flavoprotein (Fp), SDH2, FP, Succinate Dehydrogenase Complex Subunit A, Flavoprotein (Fp), Succinate Dehydrogenase [Ubiquinone] Flavoprotein Subunit, CMD1GG, MC2DN1, PGL5, SDH1, SDHA, Fp
Associations
6d
First Report of a Child With a DeSanto-Shinawi Syndrome and a Polymorphous Low-Grade Neuroepithelial Tumor of the Young. (PubMed, Am J Med Genet A)
In addition, two germinal likely pathogenic variants have been identified in the Neurofibromin 1 (NF1) and succinate dehydrogenase complex flavoprotein subunit A (SDHA) genes. Our data suggest a possible additional role of the WAC variant in early tumor development, highlighting the importance of oncogenetic testing in patients with rare neurodevelopmental syndromes and brain tumors.
Journal
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FGFR2 (Fibroblast growth factor receptor 2) • NF1 (Neurofibromin 1) • RNF20 (Ring Finger Protein 20) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
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FGFR2 fusion
19d
To screen or not to screen: complexity of SDHA mutation management. (PubMed, Endocr Oncol)
These cases underscore the importance of interpreting SDHA variants carefully, as the identification of germline SDHA variants does not always indicate the need for aggressive surveillance or intervention. Germline SDHA variants increase the risk of PPGLs and wild-type GISTs.The penetrance of germline SDHA variants in carriers without an SDHA-related tumour is low.Careful clinical assessment is essential to determine if a patient with an SDHA germline mutation has an SDHA-related tumour.This is particularly complex in GISTs, as only wild-type GISTs (those without somatic variants in c-Kit or PDGFRA) are likely to be SDHA-related.Immunohistochemistry for expression of SDH subunits can help clarify whether a tumour is related to SDHA variants.
Journal • BRCA Biomarker
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BRCA2 (Breast cancer 2, early onset) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
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PDGFRA mutation
21d
Comprehensive Analysis of Germline and Somatic SDHA Alterations Reveals Rare Incidental Germline Variants and Prognostic Implications of Somatic Loss in Breast Cancer. (PubMed, Endocr Relat Cancer)
However, CNVs extended across a 375 kb region around the SDHA locus, suggesting that this association may be related to 5p chromosomal deletions rather than the SDHA loss alone. In conclusion, germline SDHA variants are rare and likely incidental in most cancers, but somatic 5p chromosomal deletions including SDHA in breast cancer may have prognostic value.
Journal
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SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
24d
Describing the Mutational Characteristics of Myxofibrosarcoma: An AACR Project GENIE Analysis. (PubMed, Anticancer Res)
As we enter the era of precision medicine, classifying cancers by molecular markers will become increasingly valuable. Our investigation enriches the literature by identifying novel mutations and mutations exclusive to certain demographic groups. These findings support a shift beyond histology toward molecularly informed diagnostics and pathway-directed therapeutic hypotheses for MFS. Next steps should validate candidate markers in independent cohorts and link genomic profiles to clinicopathologic features, disease course, and treatment response to improve clinical translation. These observations will help shape diagnostics and targeted therapies against MFS.
Journal
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TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • ETV6 (ETS Variant Transcription Factor 6) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ATRX (ATRX Chromatin Remodeler) • NOTCH3 (Notch Receptor 3) • NCOR1 (Nuclear Receptor Corepressor 1) • FLCN (Folliculin) • ALOX12B (Arachidonate 12-Lipoxygenase) • MAP2K4 (Mitogen-Activated Protein Kinase Kinase 4) • NCOA2 (Nuclear Receptor Coactivator 2) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
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TP53 mutation • CDKN2A deletion
24d
SDHA Deficiency in Hepatocellular Carcinoma Promotes Tumor Progression through Succinate-Induced M2 Macrophage Polarization. (PubMed, Oncol Res)
SDHA deficiency leads to succinate accumulation, which promotes M2 macrophage polarization through the GPR91/STAT3 pathway, thereby facilitating HCC progression. Based on these findings, serum succinate could be a promising diagnostic biomarker for HCC.
Journal
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CXCR3 (C-X-C Motif Chemokine Receptor 3) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A) • SUCNR1 (Succinate Receptor 1)
26d
Clinical and Genetic Characteristics of Pheochromocytoma and Paraganglioma: A Single-Center Experience Including a Rare VHL Variant. (PubMed, J Clin Med)
The identification of a rare VHL c.369delG variant, previously unreported in association with PPGL, within a characteristic VHL-related clinical phenotype highlights the importance of this association. Similarly, atypical NF1 cases emphasize phenotypic variability and reinforce the importance of germline testing even in clinically silent presentations.
Journal
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NF1 (Neurofibromin 1) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
2ms
Transcriptional subtypes on immune microenvironment and predicting postoperative recurrence and metastasis in human pheochromocytoma and paraganglioma. (PubMed, Elife)
Notably, we identify ANGPT2, PCSK1N, and GPX3 as key subtype-specific biomarkers, with ANGPT2 driving tumor progression in C1 and emerging as a potential therapeutic target. Our findings provide a refined molecular classification integrating immune and genomic features in human PPGLs, offering a framework for improved prognostication and precision therapies in this rare neuroendocrine tumor type.
Journal • IO biomarker
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NF1 (Neurofibromin 1) • CD8 (cluster of differentiation 8) • VHL (von Hippel-Lindau tumor suppressor) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • SDHD (Succinate Dehydrogenase Complex Subunit D) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
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VHL mutation
2ms
Mitochondrial complex II orchestrates divergent effects in CD4+ and CD8+ T cells. (PubMed, J Clin Invest)
This metabolic reprogramming endowed SDHA-KO CD8+ T cells with superior in vivo antitumor efficacy after immune checkpoint inhibitor therapy and allogeneic SCT. These findings reveal MC II as a bifurcation point for metabolic and functional specialization in CD4+ and CD8+ T cells.
Journal • IO biomarker
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
2ms
Comprehensive Genomic Profiling of Small-Cell Lung Cancer Reveals Frequent Potentially Targetable Alterations. (PubMed, Int J Mol Sci)
TYRO3, a TAM family receptor tyrosine kinase, and SDHA, a mitochondrial enzyme involved in succinate metabolism, may contribute to tumor progression and represent emerging therapeutic vulnerabilities. These findings underscore the genomic diversity of SCLC and highlight the potential utility of broad next-generation sequencing in uncovering new molecular targets for precision therapy.
Journal
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TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1) • SOX2 • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
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PTEN mutation
3ms
Multiomics analyses of human colorectal cancer reveal changes in mitochondrial metabolism associated with chemotherapy resistance. (PubMed, Front Oncol)
We generated a chemotherapy-resistant colorectal cancer cell line, HCT-15/DOX, via doxorubicin (DOX) induction...This research highlights notable differences in mitochondrial morphology and diverse mitochondrial metabolic functions between parental and DOX-resistant HCT-15 CRC cells. The findings of the present study provide insights into the mitochondrial metabolic changes associated with CRC chemotherapy resistance, offering valuable insights into the mechanisms underlying these changes and identifying potential therapeutic targets for addressing CRC chemotherapy resistance.
Journal
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CPT1A (Carnitine Palmitoyltransferase 1A) • CRAT (Carnitine O-Acetyltransferase) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
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doxorubicin hydrochloride
3ms
EPAS1 increases SDHA to inhibit proliferation of multiple myeloma cells by restoring TCA Cycle. (PubMed, NPJ Precis Oncol)
EPAS1 enhanced SDHA expression by inhibiting HDAC2 mRNA expression and increasing acetylation at the SDHA histone H3K27 site. In conclusion, activating the EPAS1-HDAC2-SDHA axis could restore the TCA cycle as the dominant glucose metabolism pathway in order to inhibit proliferation of MM cells.
Journal
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EPAS1 (Endothelial PAS domain protein 1) • HDAC2 (Histone deacetylase 2) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
3ms
French recommendations on multi-gene panel testing in renal cell carcinoma. (PubMed, Eur J Med Genet)
Unlike hereditary predisposition to breast or colon cancer, hereditary renal cancer predispositions are rare syndromes and risk estimates are lacking for most of them. Prospective studies are needed to improve our knowledge. The GGC-PREDIR experts retained 12 genes for inclusion in the NGS MGP for renal cancer patients. However, the panel will be expanded on the basis of regularly updated data from the medical literature.
Review • Journal
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PTEN (Phosphatase and tensin homolog) • BAP1 (BRCA1 Associated Protein 1) • TSC2 (TSC complex subunit 2) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • TSC1 (TSC complex subunit 1) • FLCN (Folliculin) • SDHC (Succinate Dehydrogenase Complex Subunit C) • SDHD (Succinate Dehydrogenase Complex Subunit D) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)