SDHB Gene: Succinate Dehydrogenase Complex Iron Sulfur Subunit B
SDHB mutations predispose to hereditary paraganglioma-pheochromocytoma syndromes and gastrointestinal stromal tumors (GIST).
Gene Information Card
| Symbol | SDHB |
|---|---|
| Full Name | Succinate Dehydrogenase Complex Iron Sulfur Subunit B |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.13 |
| NCBI Gene ID | 6390 ncbi.nlm.nih.gov/gene/6390 |
| Ensembl ID | ENSG00000117118 |
| UniProt ID | P21912 |
| OMIM ID | 185470 |
| HGNC ID | 10681 |
| Aliases | IP, SDH1, SDH2, CWS1, PGL4, MC2HC |
Description
The SDHB gene encodes the iron-sulfur subunit (Ip) of succinate dehydrogenase (SDH), also known as mitochondrial complex II. This enzyme is a key component of both the tricarboxylic acid (TCA) cycle and the electron transport chain, catalyzing the oxidation of succinate to fumarate and transferring electrons to ubiquinone. SDHB is a tumor suppressor gene; germline mutations predispose to hereditary paraganglioma-pheochromocytoma syndromes (PGL4), gastrointestinal stromal tumors (GIST), and renal cell carcinoma. Loss of SDHB function leads to accumulation of succinate, which inhibits prolyl hydroxylases, stabilizing HIF1α and promoting pseudo-hypoxic signaling, angiogenesis, and tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary Paraganglioma-Pheochromocytoma Syndrome Type 4 (PGL4) | Loss of function mutations lead to succinate accumulation, HIF1α stabilization, and tumor formation in neuroendocrine tissues. | OMIM #185470; ClinVar; multiple case reports |
| Gastrointestinal Stromal Tumor (GIST) | SDHB deficiency in GIST (often wild-type for KIT/PDGFRA) results in impaired SDH complex activity and oncogenic signaling. | OMIM #606764; COSMIC; literature |
| Renal Cell Carcinoma (RCC) | SDHB mutations cause dysregulation of hypoxia-inducible factors, promoting clear cell and chromophobe RCC. | OMIM #185470; ClinVar; case studies |
| Carney-Stratakis Syndrome | Germline SDHB mutations (and other SDH genes) cause dyad of paraganglioma and GIST. | OMIM #606864; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 19.2 | Medium |
| Skeletal Muscle | 17.8 | Medium |
| Kidney | 16.5 | Medium |
| Liver | 14.3 | Medium |
| Brain | 12.1 | Medium |
| Lung | 10.5 | Low |
| Pancreas | 9.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 18.5 | Cervical adenocarcinoma; high expression |
| A549 | 15.2 | Lung carcinoma; moderate expression |
| MCF7 | 14.8 | Breast adenocarcinoma; moderate expression |
| K562 | 12.3 | Chronic myelogenous leukemia; moderate expression |
| HepG2 | 11.9 | Hepatocellular carcinoma; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.268C>T (p.Arg90*) | Nonsense | Rare (germline) | Loss of function; truncated protein; predisposes to PGL4 |
| c.423+1G>A | Splice site | Rare (germline) | Aberrant splicing; loss of function; associated with PGL4 |
| c.136C>T (p.Arg46*) | Nonsense | Rare (germline) | Loss of function; early truncation; high risk for malignant paraganglioma |
| c.725G>A (p.Arg242His) | Missense | Rare (germline) | Impaired iron-sulfur cluster binding; reduced enzyme activity; PGL4 |
| c.286G>A (p.Asp96Asn) | Missense | Rare (somatic) | Loss of function; destabilizes protein; seen in GIST |
Mutation functional classification
Loss of Function (LOF)
Most SDHB mutations are loss-of-function, leading to reduced or absent SDH enzyme activity. This causes succinate accumulation, inhibition of 2-oxoglutarate-dependent dioxygenases, and stabilization of HIF1α, driving tumorigenesis.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SDHB.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by incorporating into the SDH complex and disrupting assembly or activity, but this is not fully established.
View complete mutation data：
Gene Ontology (GO)
| • succinate dehydrogenase (ubiquinone) activity | • iron-sulfur cluster binding |
| • oxidoreductase activity | • mitochondrial electron transport |
| • succinate to ubiquinone | • tricarboxylic acid cycle |
| • cellular respiration |
Pathways
• TCA cycle (KEGG: hsa00020)
• Oxidative phosphorylation (KEGG: hsa00190)
• HIF-1 signaling pathway (KEGG: hsa04066)
• Metabolic pathways (KEGG: hsa01100)
Protein Summary
The SDHB protein is a 280-amino-acid iron-sulfur protein (Ip) that is a core component of mitochondrial complex II. It contains three iron-sulfur clusters (2Fe-2S, 4Fe-4S, and 3Fe-4S) that mediate electron transfer from succinate to ubiquinone. The protein is synthesized in the cytoplasm and imported into the mitochondrial matrix, where it assembles with SDHA, SDHC, and SDHD to form the functional complex. SDHB is essential for both the TCA cycle and oxidative phosphorylation. Mutations in SDHB are associated with hereditary cancer syndromes, and loss of protein expression is a diagnostic marker in immunohistochemistry for SDH-deficient tumors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SDHB Knockout HeLa Cell Line | EDJ-KQ18051 | Human | 6390 | Details Get a Quote |
| SDHB Knockout A-549 Cell Line | EDJ-KQ18132 | Human | 6390 | Details Get a Quote |
| SDHB Knockout HEK293 Cell Line | EDJ-KQ50618 | Human | 6390 | Details Get a Quote |
| SDHB Knockout HCT 116 Cell Line | EDJ-KQ71396 | Human | 6390 | Details Get a Quote |
| SDHB (c.201-36G>T )Point Mutation in HAP1 Cell Line | EDC03599 | Human | 6390 | Details Get a Quote |
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