Affinage

SDHB

Succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial · UniProt P21912

Length
280 aa
Mass
31.6 kDa
Annotated
2026-06-10
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SDHB encodes the iron-sulfur subunit of mitochondrial complex II (succinate dehydrogenase), and its inactivation defines a tumor-suppressor mechanism in which loss of complex II catalytic activity drives succinate accumulation and a pseudohypoxic transcriptional program (PMID:11404820, PMID:12364472, PMID:14500403). Biallelic inactivation—a germline mutation plus somatic loss of heterozygosity at the 1p36 SDHB locus—abolishes complex II enzymatic activity and upregulates hypoxia-angiogenic responsive genes (PMID:12364472, PMID:14500403). Loss of SDHB destabilizes the entire SDH complex such that the SDHB protein becomes undetectable by immunohistochemistry, making it a surrogate marker of complex integrity (PMID:19576851). At the protein level, common disease-causing missense mutations do not impair intrinsic enzymatic function or complex assembly but accelerate proteasomal degradation, frequently by disrupting binding of the cochaperone HSC20 to the L(I)YR Fe-S transfer motif, thereby blocking iron-sulfur cluster delivery (PMID:22835832, PMID:26719882). SDHB loss reprograms cell metabolism toward glycolysis and reductive glutamine carboxylation, raises mitochondrial ROS, and stabilizes HIF1α under normoxia, an axis that in chromaffin cells elevates catecholamine secretion (PMID:18519664, PMID:26620190, PMID:26719882). Succinate accumulation and associated DNA/histone hypermethylation underlie a CpG island methylator phenotype, including epigenetic silencing of KRT19, and an EMT-like program—via nuclear Snail1/2 and a SNAIL1-SMAD3/4 repressor complex—that promotes invasion and migration (PMID:22492777, PMID:26460615, PMID:26719882, PMID:27816688). SDHB loss also dysregulates iron and copper homeostasis, generating oxidative stress that can be selectively exploited by high-dose ascorbate (PMID:34127497, PMID:32152203). Genetic dissection in mice shows that SDHB disruption alone produces succinate accumulation but not 5hmC loss, HIF accumulation, or tumors; frank pheochromocytoma requires cooperative loss of NF1 (PMID:35235785). Biallelic SDHB loss also causes severe isolated complex II deficiency with leukodystrophy (PMID:22972948).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2003 High

    Established SDHB as a two-hit tumor suppressor whose biallelic inactivation abolishes complex II activity and activates the hypoxic/angiogenic program, answering how an Fe-S subunit mutation predisposes to paraganglioma.

    Evidence Mutation/LOH analysis with respiratory chain enzyme assays and IHC/ISH on familial pheochromocytoma tumors

    PMID:11404820 PMID:12364472 PMID:14500403

    Open questions at the time
    • Did not define how succinate accumulation links to the hypoxic program
    • Correlative pathway activation in tumor tissue, not mechanistic manipulation
  2. 2008 High

    Showed by direct knockdown that SDHB loss causes glycolytic shift, HIF-1α/HIF-2α stabilization, stress kinase activation, and altered ECM adhesion, moving from correlation to a causal cellular phenotype.

    Evidence siRNA knockdown with respirometry, microarray, adhesion assays and transient HIF-1α rescue

    PMID:18519664

    Open questions at the time
    • HIF-1α silencing only partially reversed adhesion
    • Performed in a non-chromaffin cell context
  3. 2009 High

    Demonstrated that any SDH subunit mutation destabilizes the whole complex including SDHB, validating SDHB IHC as a surrogate for complex integrity.

    Evidence IHC on 220 tumors with known mutation status across multiple cohorts

    PMID:19576851

    Open questions at the time
    • Did not resolve the molecular degradation pathway
    • Does not distinguish missense from truncating consequences
  4. 2012 High

    Resolved the protein-level basis of missense pathogenicity—accelerated degradation rather than catalytic impairment—while showing mutant SDHB retains localization and SDHA binding.

    Evidence Pulse-chase, co-IP, colocalization and HDAC-inhibitor rescue in transfected HeLa cells

    PMID:22835832

    Open questions at the time
    • Did not identify the responsible E3/quality-control machinery
    • Used overexpression in a heterologous cell line
  5. 2012 Medium

    Linked SDHB mutation specifically to EMT activation in metastatic tumors, identifying a transcriptional invasion program.

    Evidence EMT-panel transcriptomics and Snail1/2 IHC on tumor cohorts; reciprocal KD/OE with SNAIL1-SMAD3/4 identification in colorectal cells

    PMID:22492777 PMID:27816688

    Open questions at the time
    • Tumor data correlative without SDHB manipulation
    • SMAD3/4 mechanism shown in colorectal, not chromaffin, cells
  6. 2015 High

    Defined KRT19 epigenetic silencing as a downstream effector of SDHB-loss-driven invasiveness and confirmed the ROS→HIF1α→catecholamine axis.

    Evidence Sdhb-knockout chromaffin cells with KRT19 rescue/knockdown and bisulfite sequencing; PC12 knockdown with NAC and HIF1α rescue

    PMID:26460615 PMID:26620190

    Open questions at the time
    • Direct link from succinate to KRT19 methylation not fully mapped
    • Catecholamine axis demonstrated in PC12 cells only
  7. 2016 High

    Pinpointed disruption of HSC20 binding to the LYR Fe-S transfer motif as the degradation trigger and characterized the metabolic state (succinate accumulation, reductive carboxylation, HIF1α, CIMP) of an SDHB-null line.

    Evidence Stable isotope-resolved metabolomics, co-chaperone binding assay and bioinformatics in an SDHB-deficient RCC line

    PMID:26719882

    Open questions at the time
    • Single cell-line context
    • Did not determine why HIF1α rather than HIF2α dominates
  8. 2021 Medium

    Distinguished SDHB-specific consequences from SDHD loss, tying SDHB deficiency to iron/copper dysregulation, stronger hypermethylation, and selective ascorbate vulnerability.

    Evidence Comparative Sdhb vs Sdhd knockout chromaffin cells with metabolic, ROS and iron/copper assays plus ascorbate treatment; iron-transport protein analysis with in vivo allograft

    PMID:32152203 PMID:34127497

    Open questions at the time
    • Mechanism of subunit-specific iron handling unresolved
    • Therapeutic ascorbate effect from single-lab models
  9. 2022 High

    Demonstrated by in vivo genetic epistasis that SDHB loss alone is insufficient for tumorigenesis and requires cooperative NF1 loss, refining the multi-hit tumor model.

    Evidence Conditional adrenal-medulla SDHB knockout and SDHB/NF1 double-knockout mouse models with ascorbate-depletion survival assay

    PMID:35235785

    Open questions at the time
    • Why succinate accumulation alone fails to drive 5hmC loss/HIF in vivo unexplained
    • Other cooperating lesions beyond NF1 not surveyed

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how succinate accumulation is mechanistically coupled to the specific epigenetic and metabolic vulnerabilities, and which protein quality-control machinery executes mutant SDHB degradation.
  • E3 ligase/degradation pathway for mutant SDHB unidentified
  • Direct succinate-to-target dioxygenase epistasis not fully mapped
  • Cooperating drivers beyond NF1 uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 7 GO:0140098 catalytic activity, acting on RNA 3
Localization
GO:0005739 mitochondrion 3
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-1643685 Disease 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
HSC20NF1SDHA
Complex memberships
Succinate dehydrogenase (mitochondrial complex II)

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Inactivating germline SDHB mutations cause loss of complex II catalytic activity, establishing SDHB as part of the catalytic core of succinate dehydrogenase (mitochondrial complex II) and a tumor suppressor gene whose disruption predisposes to pheochromocytoma and paraganglioma. Mutation analysis (sequencing) of familial pheochromocytoma kindreds; functional context from known complex II biochemistry American journal of human genetics Medium 11404820
2002 A germline SDHB missense mutation combined with somatic loss of heterozygosity at 1p36 (SDHB locus) resulted in complete loss of mitochondrial complex II enzymatic activity in a pheochromocytoma, accompanied by upregulation of hypoxia-angiogenic responsive genes (pseudohypoxia), demonstrating that biallelic SDHB inactivation abolishes complex II function and activates the hypoxic/angiogenic pathway. LOH analysis, respiratory chain enzyme assay, in situ hybridization, immunohistochemistry on tumor tissue The Journal of clinical endocrinology and metabolism High 12364472
2003 Deleterious SDHB germline mutations in pheochromocytoma are associated with complete loss of complex II catalytic activity in tumor tissue and LOH at chromosome 1p36 (SDHB locus), confirming SDHB as a tumor suppressor following a two-hit mechanism. Respiratory chain enzyme assay, LOH analysis, immunohistochemistry on tumor samples Cancer research High 14500403
2008 SDHB silencing by DNA-based siRNA impaired cellular respiration, caused a shift to glycolysis, upregulated HIF-1α and HIF-2α (pseudohypoxia), hyperphosphorylated JNK and p38 stress kinases, and increased cell adhesion to extracellular matrix components (fibronectin, laminin); partial reversal of the adhesion phenotype by transient HIF-1α silencing implicated HIF-1 in this process. RNA interference (siRNA knockdown), respirometry, microarray, Western blot, cell adhesion assay, transient HIF-1α knockdown Cancer research High 18519664
2009 SDHB protein expression is absent by immunohistochemistry in tumors harboring SDHB, SDHC, or SDHD mutations but is retained in tumors from MEN2, VHL, and NF1 patients, demonstrating that loss of any SDH subunit destabilizes the whole complex including the SDHB subunit, making SDHB IHC a surrogate marker for SDH complex integrity. Immunohistochemistry on 220 tumors with known mutation status (retrospective and prospective series) The Lancet. Oncology High 19576851
2012 Common SDHB missense mutations do not impair mRNA expression or intrinsic enzymatic function, but reduce protein half-life (accelerated degradation), demonstrated by pulse-chase assay; the mutant SDHB protein retains correct mitochondrial localization and the ability to co-immunoprecipitate with SDHA, indicating complex formation is intact. Treatment with HDAC inhibitors extended mutant protein half-life, implicating the protein quality control machinery in SDHB degradation. Pulse-chase assay in transfected HeLa cells, RT-PCR, Western blot, subcellular colocalization, co-immunoprecipitation, HDAC inhibitor treatment FASEB journal High 22835832
2012 SDHB mutations are associated with activation of epithelial-to-mesenchymal transition (EMT) in metastatic pheochromocytomas/paragangliomas, evidenced by upregulation of LOXL2, TWIST, TCF3, MMP2, MMP1 and downregulation of KRT19 and CDH2, with nuclear translocation of Snail1/2 specifically in SDHB-mutated metastatic tumors. Transcriptomic profiling of 188 tumor samples (94-gene EMT panel), immunohistochemistry (Snail1/2) in 93 tumors The Journal of clinical endocrinology and metabolism Medium 22492777
2012 Homozygous SDHB mutation (p.Asp48Val) in a patient causes severe isolated mitochondrial complex II deficiency with hypotonia and leukodystrophy; Western blot and BN-PAGE confirmed decreased steady-state SDHB protein and impaired complex II assembly; yeast complementation studies confirmed pathogenicity. Western blot, BN-PAGE, enzyme activity assay, yeast complementation Journal of medical genetics High 22972948
2015 In Sdhb-knockout mouse chromaffin cells, loss of SDHB produced increased individual cell migration (faster motility, increased persistence), invasiveness, and adhesion; this phenotype was associated with epigenetic silencing (hypermethylation) of Krt19 and EMT-like reprogramming (modulation of Twist1, Twist2, Tcf3, Snai1, N-cadherin). KRT19 rescue by lentiviral transduction reduced invasion, and KRT19 knockdown in wild-type cells increased invasion, establishing KRT19 as a downstream effector of SDHB loss-driven invasiveness. Sdhb knockout in mouse chromaffin cells, migration/invasion assays, lentiviral KRT19 rescue, siRNA KRT19 knockdown, bisulfite sequencing, demethylating agent treatment Oncotarget High 26460615
2015 SDHB silencing in PC12 pheochromocytoma cells abolishes complex II activity, increases ROS production and stabilizes nuclear HIF1α under normoxia; these effects increase tyrosine hydroxylase activity and catecholamine secretion. Pretreatment with NAC (ROS scavenger) or HIF1α knockdown abolishes these phenotypes, establishing an ROS→HIF1α→catecholamine axis downstream of SDHB loss. siRNA knockdown in PC12 cells, complex II activity assay, ROS measurement, catecholamine secretion assay, NAC treatment, HIF1α siRNA rescue Neurochemical research High 26620190
2016 The SDHB R46Q mutation in an SDHB-deficient renal cell carcinoma line (UOK269) disrupts binding of the cochaperone HSC20 to the L(I)YR Fe-S transfer motif in SDHB, causing rapid SDHB degradation and loss of SDH activity. In the absence of SDHB, succinate accumulates (351.4 ± 63.2 nmol/mg), respiration is undetectable, glutamine becomes the main TCA substrate via reductive carboxylation, HIF1α (not HIF2α) increases, and a CpG island methylator phenotype (CIMP) develops. Bioinformatic screening showed 37% of disease-causing SDHB missense mutations affect LYR Fe-S transfer motifs or Fe-S cluster-ligating cysteines. Stable isotope-resolved metabolomics, biochemical co-chaperone binding assay, respiration assay, Western blot, bioinformatics in novel SDHB-deficient RCC cell line Journal of the National Cancer Institute High 26719882
2013 SDHB mRNA undergoes C-to-U coding RNA editing (C136U, R46X) in peripheral blood monocytes; this editing is markedly upregulated by hypoxia (1% O2) and during macrophage differentiation, representing an epigenetic post-transcriptional mechanism that downregulates SDHB function in monocytes during hypoxia adaptation. CD14-positive monocytes are the principal editing cell type; CD14-negative lymphocytes show no editing. Allele-specific quantitative PCR, flow cytometry, immunologic cell separation, gene expression microarray, high-throughput RNA sequencing, hypoxia exposure experiments PeerJ Medium 24058882
2016 SDHB deficiency in colorectal cancer cells promotes cell migration and invasion through EMT enabled by upregulation of the transcriptional repression complex SNAIL1-SMAD3/SMAD4, activating TGFβ signaling. SDHB knockdown increased migration/invasion, while SDHB overexpression reversed this; SNAIL1-SMAD3/SMAD4 was identified as the downstream mediator. siRNA knockdown, overexpression, transwell migration/invasion assays, Western blot, pathway analysis in colorectal cancer cells Translational oncology Medium 27816688
2020 TET2 loss (induced by low shear stress) upregulates SDHB expression and activity by decreasing recruitment of histone deacetylase 2 to the SDHB promoter (independent of DNA demethylation), leading to SDHB-mediated mitochondrial injury, increased ROS, and vascular endothelial cell pyroptosis; ROS scavenger NAC rescued pyroptosis, placing SDHB downstream of TET2 in a TET2/SDHB/ROS pathway. TET2 shRNA, SDHB overexpression, NAC treatment, HDAC2 recruitment assay, mitochondrial ROS measurement, pyroptosis assay in HUVECs Free radical biology & medicine Medium 33248263
2020 SDHB overexpression in endothelial cells enhances pyroptosis and mitochondrial ROS production; this effect is blocked by the ROS scavenger NAC, establishing that SDHB-driven ROS mediates endothelial cell pyroptosis in the context of TMAO-induced atherosclerosis. SDHB overexpression in HUVECs, NAC treatment, ROS assay, pyroptosis assay, apoE-/- mouse model Journal of cellular physiology Medium 32012263
2021 Loss of SDHB specifically (compared to SDHD loss) leads to dysregulated iron and copper homeostasis, increased oxidative stress, and hallmarks of mesenchymal transition associated with stronger DNA hypermethylation and pseudo-hypoxic phenotype, without NRF2 activation. High-dose ascorbate exacerbated mitochondrial ROS selectively in Sdhb-deficient cells, causing cell death, establishing a mechanistic link between SDHB loss, iron overload, and ROS accumulation distinct from SDHD loss. Sdhb and Sdhd knockout chromaffin cell lines, metabolic analysis, ROS assay, iron/copper homeostasis measurements, ascorbate treatment, comparative SDHB vs SDHD cell analysis Cancer research High 34127497
2022 Mouse adrenal medulla-specific SDHB disruption recapitulates succinate accumulation but does NOT cause 5hmC loss, HIF accumulation, or tumorigenesis on its own. Concomitant SDHB and NF1 disruption yields SDHx-like pheochromocytomas, demonstrating that SDHB loss requires additional growth-regulatory pathway activation (NF1 loss) for tumorigenesis. In vitro, 2-OG dioxygenase cofactor ascorbate depletion reduces SDHB-deficient cell survival. Conditional mouse SDHB knockout, double SDHB/NF1 knockout mouse model, in vivo tumor analysis, ascorbate depletion cell survival assay Cell reports High 35235785
2021 Loss of sdhb in zebrafish larvae (CRISPR/cas9 truncating mutation) decreases mitochondrial complex II activity and causes significant succinate accumulation, recapitulating the metabolic phenotype of human SDHB-associated paragangliomas in a vertebrate model. CRISPR/cas9 zebrafish knockout, complex II enzymatic activity assay, metabolomic analysis (succinate measurement), behavioral and morphological phenotyping Endocrine-related cancer High 33156815
2014 SDHB germline mutations in metastatic pheochromocytoma/paraganglioma are associated with hypermethylation of the MGMT promoter and low MGMT expression, which correlates with responsiveness to temozolomide chemotherapy; partial responses to TMZ were observed only in SDHB-mutated patients. Retrospective clinical study, MGMT immunohistochemistry, MGMT promoter methylation analysis in 190 PPGLs, survival/response analysis International journal of cancer Medium 24752622
2019 SDHB-deficient pheochromocytoma cells (with pseudohypoxia from SDHB loss) display elevated expression of iron transport proteins (transferrin, TFR2, DMT1/SLC11A2), leading to iron accumulation and elevated oxidative stress; pharmacological ascorbic acid disrupts redox homeostasis, induces DNA oxidative damage and apoptosis selectively in SDHB-low cells, and suppresses metastatic lesions in a mouse allograft model. Western blot for iron transport proteins, ROS/oxidative stress assays, ascorbic acid treatment in vitro and in vivo (mouse allograft model), survival analysis Clinical cancer research Medium 32152203
2018 SDHB-deficient cluster I PCPGs develop dependency on mitochondrial complex I and enhanced NAD+ metabolism; this supports chemoresistance via the PARP1/BER DNA repair pathway. Combining a PARP inhibitor with temozolomide improved cytotoxicity, reduced metastatic lesions, and prolonged survival in mice with SDHB-knockdown PCPG allografts. Transcriptomic profiling of clinical specimens, PARP inhibitor + TMZ combination in vitro and in vivo (mouse allograft), NAD+ pathway analysis Clinical cancer research Medium 29636359
2015 Carney triad tumors and Sdhb+/- mouse gastrointestinal tissues share an identical mitochondrial structural phenotype (loss of cristae, structural abnormalities, variable size) with SDH-deficient tumors, establishing that SDHB haploinsufficiency is sufficient to produce abnormal mitochondrial morphology (hypoxic mitochondrial phenotype) in vivo. Electron microscopy of human tumors (CTr, CSS, isolated GIST) and Sdhb+/- mouse GI tissue Endocrine-related cancer Medium 25808178

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. American journal of human genetics 885 11404820
2004 Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. JAMA 736 15328326
2003 Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas. Cancer research 453 14500403
2009 An immunohistochemical procedure to detect patients with paraganglioma and phaeochromocytoma with germline SDHB, SDHC, or SDHD gene mutations: a retrospective and prospective analysis. The Lancet. Oncology 424 19576851
2007 Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD. European journal of human genetics : EJHG 353 17667967
2011 Plasma methoxytyramine: a novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status. European journal of cancer (Oxford, England : 1990) 283 22036874
2010 Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD. Human mutation 272 19802898
2002 Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas. Journal of medical genetics 270 11897817
2008 Germline SDHB mutations and familial renal cell carcinoma. Journal of the National Cancer Institute 265 18728283
2010 Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes. Human pathology 212 20236688
2018 Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD. Journal of medical genetics 203 29386252
2002 Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma. The Journal of clinical endocrinology and metabolism 182 12364472
2014 SDHB mutations are associated with response to temozolomide in patients with metastatic pheochromocytoma or paraganglioma. International journal of cancer 162 24752622
2020 Trimethylamine N-oxide promotes apoE-/- mice atherosclerosis by inducing vascular endothelial cell pyroptosis via the SDHB/ROS pathway. Journal of cellular physiology 120 32012263
2012 Risk of malignant paraganglioma in SDHB-mutation and SDHD-mutation carriers: a systematic review and meta-analysis. Journal of medical genetics 113 23099648
2016 SDHB-Deficient Cancers: The Role of Mutations That Impair Iron Sulfur Cluster Delivery. Journal of the National Cancer Institute 97 26719882
2012 Recessive germline SDHA and SDHB mutations causing leukodystrophy and isolated mitochondrial complex II deficiency. Journal of medical genetics 96 22972948
2007 Malignant head and neck paragangliomas in SDHB mutation carriers. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery 94 17599579
2003 Novel succinate dehydrogenase subunit B (SDHB) mutations in familial phaeochromocytomas and paragangliomas, but an absence of somatic SDHB mutations in sporadic phaeochromocytomas. Oncogene 94 12618761
2012 Epithelial to mesenchymal transition is activated in metastatic pheochromocytomas and paragangliomas caused by SDHB gene mutations. The Journal of clinical endocrinology and metabolism 93 22492777
2006 Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma. BMC medical genetics 86 16405730
2003 Genetic analysis of mitochondrial complex II subunits SDHD, SDHB and SDHC in paraganglioma and phaeochromocytoma susceptibility. Clinical endocrinology 86 14974914
2023 Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement. Nature reviews. Endocrinology 85 38097671
2014 Fitness and competitive ability of Botrytis cinerea field isolates with dual resistance to SDHI and QoI fungicides, associated with several sdhB and the cytb G143A mutations. Phytopathology 83 24168041
2008 Cells silenced for SDHB expression display characteristic features of the tumor phenotype. Cancer research 81 18519664
2017 SDHB-related pheochromocytoma and paraganglioma penetrance and genotype-phenotype correlations. Journal of cancer research and clinical oncology 71 28374168
2018 Targeting NAD+/PARP DNA Repair Pathway as a Novel Therapeutic Approach to SDHB-Mutated Cluster I Pheochromocytoma and Paraganglioma. Clinical cancer research : an official journal of the American Association for Cancer Research 68 29636359
2016 SDHB mutation status and tumor size but not tumor grade are important predictors of clinical outcome in pheochromocytoma and abdominal paraganglioma. Surgery 65 27839933
2010 Paraganglioma, neuroblastoma, and a SDHB mutation: Resolution of a 30-year-old mystery. American journal of medical genetics. Part A 61 20503330
2019 Incidence of succinate dehydrogenase and fumarate hydratase-deficient renal cell carcinoma based on immunohistochemical screening with SDHA/SDHB and FH/2SC. Human pathology 60 31299266
2016 SDHB deficiency promotes TGFβ-mediated invasion and metastasis of colorectal cancer through transcriptional repression complex SNAIL1-SMAD3/4. Translational oncology 60 27816688
2012 Overexpression of insulin-like growth factor 1 receptor and frequent mutational inactivation of SDHA in wild-type SDHB-negative gastrointestinal stromal tumors. Genes, chromosomes & cancer 60 23109135
2013 Evaluation of SDHB, SDHD and VHL gene susceptibility testing in the assessment of individuals with non-syndromic phaeochromocytoma, paraganglioma and head and neck paraganglioma. Clinical endocrinology 59 23072324
2021 Loss of SDHB Promotes Dysregulated Iron Homeostasis, Oxidative Stress, and Sensitivity to Ascorbate. Cancer research 58 34127497
2017 The penetrance of paraganglioma and pheochromocytoma in SDHB germline mutation carriers. Clinical genetics 58 28503760
2014 The size of the primary tumor and age at initial diagnosis are independent predictors of the metastatic behavior and survival of patients with SDHB-related pheochromocytoma and paraganglioma: a retrospective cohort study. BMC cancer 58 25048685
2015 Deciphering the molecular basis of invasiveness in Sdhb-deficient cells. Oncotarget 57 26460615
2012 The microRNA expression changes associated with malignancy and SDHB mutation in pheochromocytoma. Endocrine-related cancer 57 22241719
2004 Molecular genetic analysis of FIH-1, FH, and SDHB candidate tumour suppressor genes in renal cell carcinoma. Journal of clinical pathology 57 15220362
2020 Low shear stress induced vascular endothelial cell pyroptosis by TET2/SDHB/ROS pathway. Free radical biology & medicine 56 33248263
2010 SDHB loss predicts malignancy in pheochromocytomas/sympathethic paragangliomas, but not through hypoxia signalling. Endocrine-related cancer 52 20702724
1992 SDH1, the gene encoding the succinate dehydrogenase flavoprotein subunit from Saccharomyces cerevisiae. Gene 52 1511876
2014 The presence of SDHB mutations should modify surgical indications for carotid body paragangliomas. Annals of surgery 50 24169168
2012 Missense mutations in the human SDHB gene increase protein degradation without altering intrinsic enzymatic function. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 47 22835832
2010 Mutation of SDHB is a cause of hypoxia-related high-altitude paraganglioma. Clinical cancer research : an official journal of the American Association for Cancer Research 46 20592014
2010 Low penetrance of a SDHB mutation in a large Dutch paraganglioma family. BMC medical genetics 45 20540712
2012 Elevated plasma succinate in PTEN, SDHB, and SDHD mutation-positive individuals. Genetics in medicine : official journal of the American College of Medical Genetics 43 22261759
2020 Melatonin alleviates progression of uterine endometrial cancer by suppressing estrogen/ubiquitin C/SDHB-mediated succinate accumulation. Cancer letters 42 32061949
2017 miR-142-5p promotes development of colorectal cancer through targeting SDHB and facilitating generation of aerobic glycolysis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 42 28622713
2020 Therapeutic Targeting of SDHB-Mutated Pheochromocytoma/Paraganglioma with Pharmacologic Ascorbic Acid. Clinical cancer research : an official journal of the American Association for Cancer Research 41 32152203
2020 Clinical characteristics and outcomes of SDHB-related pheochromocytoma and paraganglioma in children and adolescents. Journal of cancer research and clinical oncology 40 32062700
2017 The phenotype of SDHB germline mutation carriers: a nationwide study. European journal of endocrinology 40 28490599
2017 The utility of SDHB and FH immunohistochemistry in patients evaluated for hereditary paraganglioma-pheochromocytoma syndromes. Human pathology 40 29079178
2014 Germline PTEN, SDHB-D, and KLLN alterations in endometrial cancer patients with Cowden and Cowden-like syndromes: an international, multicenter, prospective study. Cancer 39 25376524
2004 Investigation of the role of SDHB inactivation in sporadic phaeochromocytoma and neuroblastoma. British journal of cancer 39 15505628
2015 15 YEARS OF PARAGANGLIOMA: Genetics and mechanism of pheochromocytoma-paraganglioma syndromes characterized by germline SDHB and SDHD mutations. Endocrine-related cancer 38 26113606
2005 Mutations of the SDHB and SDHD genes. Familial cancer 36 15883710
2011 Succinate Dehydrogenase Subunit B (SDHB) Is Expressed in Neurofibromatosis 1-Associated Gastrointestinal Stromal Tumors (Gists): Implications for the SDHB Expression Based Classification of Gists. Journal of Cancer 35 21479127
2021 SDHB Suppresses the Tumorigenesis and Development of ccRCC by Inhibiting Glycolysis. Frontiers in oncology 34 34094922
2022 SDHB knockout and succinate accumulation are insufficient for tumorigenesis but dual SDHB/NF1 loss yields SDHx-like pheochromocytomas. Cell reports 33 35235785
2009 Contrasting clinical manifestations of SDHB and VHL associated chromaffin tumours. Endocrine-related cancer 33 19208735
2012 High prevalence of occult paragangliomas in asymptomatic carriers of SDHD and SDHB gene mutations. European journal of human genetics : EJHG 31 22948026
2009 The first Dutch SDHB founder deletion in paraganglioma-pheochromocytoma patients. BMC medical genetics 31 19368708
2019 γ-Tocotrienol inhibits oxidative phosphorylation and triggers apoptosis by inhibiting mitochondrial complex I subunit NDUFB8 and complex II subunit SDHB. Toxicology 30 30769052
2017 Calculating the optimal surveillance for head and neck paraganglioma in SDHB-mutation carriers. Familial cancer 29 27573198
2017 The microenvironment induces collective migration in SDHB-silenced mouse pheochromocytoma spheroids. Endocrine-related cancer 29 28830936
2015 Loss of SDHB Elevates Catecholamine Synthesis and Secretion Depending on ROS Production and HIF Stabilization. Neurochemical research 29 26620190
2020 Targeting NRF2-Governed Glutathione Synthesis for SDHB-Mutated Pheochromocytoma and Paraganglioma. Cancers 28 31979226
2020 A xenograft and cell line model of SDH-deficient pheochromocytoma derived from Sdhb+/- rats. Endocrine-related cancer 27 32252027
2013 Hypoxia-inducible C-to-U coding RNA editing downregulates SDHB in monocytes. PeerJ 26 24058882
2023 Resistance Risk and Resistance-Related Point Mutation in SdhB and SdhC1 of Cyclobutrifluram in Fusarium pseudograminearum. Journal of agricultural and food chemistry 25 36657474
2019 Variant type is associated with disease characteristics in SDHB, SDHC and SDHD-linked phaeochromocytoma-paraganglioma. Journal of medical genetics 24 31492822
2018 Primary fibroblast co-culture stimulates growth and metabolism in Sdhb-impaired mouse pheochromocytoma MTT cells. Cell and tissue research 24 30159755
2006 Paraganglioma syndrome: SDHB, SDHC, and SDHD mutations in head and neck paragangliomas. Annals of the New York Academy of Sciences 24 17102086
2020 Heterokaryotic state of a point mutation (H249Y) in SDHB protein drives the evolution of thifluzamide resistance in Rhizoctonia solani. Pest management science 23 33098218
2017 Characterization of boscalid-resistance conferring mutations in the SdhB subunit of respiratory complex II and impact on fitness and mycotoxin production in Penicillium expansum laboratory strains. Pesticide biochemistry and physiology 23 28456312
2017 Renal cell carcinoma with angioleiomyoma-like stroma and clear cell papillary renal cell carcinoma: exploring SDHB protein immunohistochemistry and the relationship to tuberous sclerosis complex. Human pathology 23 29180251
2017 Persistent Severe Hyperlactatemia and Metabolic Derangement in Lethal SDHB-Mutated Metastatic Kidney Cancer: Clinical Challenges and Examples of Extreme Warburg Effect. JCO precision oncology 22 35172488
2004 SDHB, SDHC, and SDHD mutation screen in sporadic and familial head and neck paragangliomas. Clinical genetics 22 15479192
2025 Multi-omic analysis of SDHB-deficient pheochromocytomas and paragangliomas identifies metastasis and treatment-related molecular profiles. Nature communications 21 40097403
2015 Role of microenvironment on neuroblastoma SK-N-AS SDHB-silenced cell metabolism and function. Endocrine-related cancer 21 25808177
2022 Loss of SDHB Induces a Metabolic Switch in the hPheo1 Cell Line toward Enhanced OXPHOS. International journal of molecular sciences 20 35008989
2020 Glutaminases as a Novel Target for SDHB-Associated Pheochromocytomas/Paragangliomas. Cancers 20 32150977
2019 Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers. Cancers 20 30658386
2018 Germline SDHB and SDHD mutations in pheochromocytoma and paraganglioma patients. Endocrine connections 20 30352407
2017 Loss of maternal chromosome 11 is a signature event in SDHAF2, SDHD, and VHL-related paragangliomas, but less significant in SDHB-related paragangliomas. Oncotarget 20 28099933
2015 Carney triad, SDH-deficient tumors, and Sdhb+/- mice share abnormal mitochondria. Endocrine-related cancer 20 25808178
2018 An Assembly Factor Promotes Assembly of Flavinated SDH1 into the Succinate Dehydrogenase Complex. Plant physiology 19 29930107
2023 Research progress on the pathogenesis of the SDHB mutation and related diseases. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 18 37734265
2019 Diffusion-weighted imaging (DWI) highlights SDHB-related tumours: A pilot study. Clinical endocrinology 18 30934121
2016 Leukoencephalopathy due to Complex II Deficiency and Bi-Allelic SDHB Mutations: Further Cases and Implications for Genetic Counselling. JIMD reports 18 27604842
2004 K40E: a novel succinate dehydrogenase (SDH)B mutation causing familial phaeochromocytoma and paraganglioma. Clinical endocrinology 18 15473885
2015 Lack of utility of SDHB mutation testing in adrenergic metastatic phaeochromocytoma. European journal of endocrinology 17 25371406
2022 An exploration in pitfalls in interpreting SDHB immunohistochemistry. Histopathology 16 35546442
2022 Kidney tumors associated with germline mutations of FH and SDHB show a CpG island methylator phenotype (CIMP). PloS one 16 36455002
2021 SDHB variant type impacts phenotype and malignancy in pheochromocytoma-paraganglioma. Journal of medical genetics 16 34750193
2019 MicroRNA-96-3p promotes metastasis of papillary thyroid cancer through targeting SDHB. Cancer cell international 16 31749660
2007 Novel germline mutations in the SDHB and SDHD genes in Japanese pheochromocytomas. Hormone research 16 17308434
2021 Loss of sdhb in zebrafish larvae recapitulates human paraganglioma characteristics. Endocrine-related cancer 15 33156815
2005 There is no evidence that the SDHB gene is involved in neuroblastoma development. Oncology research 15 16491957

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