SDHB (succinate dehydrogenase complex II, subunit B, iron-sulfur protein or IP)
2002-04-01 Anne-Paule Gimenez-Roqueplo AffiliationDépartement de Génétique Moléculaire, Hôpital Européen Georges Pompidou, 20-40, rue Leblanc, 75908 Paris cedex 15, France
Identity
HGNC
LOCATION
1p36.13
IMAGE
LEGEND
Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics
LOCUSID
ALIAS
CWS2,IP,MC2DN4,PGL4,SDH,SDH1,SDH2,SDHIP
FUSION GENES
DNA/RNA
Description
1123 bp, 8 exons
Proteins
Expression
widely expressed
Localisation
mitochondrial inner membrane
Function
The complex II (succinate-ubiquinone oxidoreductase) is un key component of the mitochondrial respiratory chain and the tricarboxylic acid cycle. It is involved in the oxidation of succinate (succinate + ubiquinone = fumarate + ubiquinol) and carries electrons from FADH to CoQ. It is composed of four nuclear-encoded subunits. The subunit B protein or iron-sulfur protein, which binds three different iron-sulfur clusters, is directly involved in the catalytic activity of succinate dehydrogenase.
Mutations
Germinal
Germline mutations cause hereditary paraganglioma, non-familial paraganglioma, familial and sporadic pheochromocytomas. Different germline mutations have been reported: i) a nonsense mutation (R90X) in a family with cervical paraganglioma and ectopic pheochromocytoma, ii) a missense mutation (P197R) in a family with extraadrenal pheochromocytoma and a 1bp deletion in a sporadic pheochromocytoma, iii) a missense (P131R) mutation and 1 bp insertion (M71fsX80) in familial paraganglioma and a nonsense mutation (Q59X) in sporadic paraganglioma.
Somatic
Loss of wild type allele in tumor DNA is usually observed.
Implicated in
Entity name
Hereditary paraganglioma type 4
Note
Alias: Familial non chromaffin paragangliomas 4; Familial glomus tumor; Familial and sporadic pheochromocytoma
Disease
Hereditary paraganglioma type 4 (PGL4) is a rare autosomal dominant disorder non maternally imprinted. Paragangliomas are slow growing highly vascular tumor, usually benigns, derived from crest-neural cells. They are preferentially located in the neck (carotid body and glomus vagal) and head (glomus jugulare and tympanicum). They may be associated with adrenal or extraadrenal pheochromocytomas which produce catecholamines.
Prognosis
It depends on extent of the disease at the time of diagnosis.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 11404820 | 2001 | Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. | Astuti D et al |
| 7622059 | 1995 | Structural organization of the gene encoding the human iron-sulfur subunit of succinate dehydrogenase. | Au HC et al |
| 11897817 | 2002 | Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas. | Baysal BE et al |
| 17379520 | 2007 | RASSF1A is part of a complex similar to the Drosophila Hippo/Salvador/Lats tumor-suppressor network. | Guo C et al |
| 8291026 | 1993 | The gene for the iron sulfur protein of succinate dehydrogenase (SDH-IP) maps to human chromosome 1p35-36.1. | Leckschat S et al |
Other Information
Locus ID:
NCBI: 6390
MIM: 185470
HGNC: 10681
Ensembl: ENSG00000117118
Variants:
dbSNP: 6390
ClinVar: 6390
TCGA: ENSG00000117118
COSMIC: SDHB
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000117118 | ENST00000375499 | P21912 |
| ENSG00000117118 | ENST00000463045 | A0A087WXX8 |
| ENSG00000117118 | ENST00000491274 | A0A087WWT1 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA165543618 | SDHAF2 | Gene | DataAnnotation | associated | |||
| PA35607 | SDHC | Gene | DataAnnotation | associated | |||
| PA35608 | SDHD | Gene | DataAnnotation | associated | |||
| PA445229 | Paraganglioma | Disease | DataAnnotation | associated | |||
| PA445315 | Pheochromocytoma | Disease | DataAnnotation | associated |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38097671 | 2024 | Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement. | 2 |
| 38097671 | 2024 | Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement. | 2 |
| 34750193 | 2023 | SDHB variant type impacts phenotype and malignancy in pheochromocytoma-paraganglioma. | 2 |
| 36346292 | 2023 | High rates of the SDHB p.Arg46Gln pathogenic variant predisposes New Zealand Māori to phaeochromocytoma/paraganglioma. | 0 |
| 36652439 | 2023 | Evidence for a Founder Effect of SDHB Exon 1 Deletion in Brazilian Patients With Paraganglioma. | 1 |
| 36763043 | 2023 | Metabolic Characterization and Glyceraldehyde-3-Phosphate Dehydrogenase-Dependent Regulation of Epithelial Sodium Channels in hPheo1 Wild-type and SDHB Knockdown Cells. | 0 |
| 36786389 | 2023 | Distortion in transmission of pathogenic SDHB- and SDHD-mutated alleles from parent to offspring. | 0 |
| 34750193 | 2023 | SDHB variant type impacts phenotype and malignancy in pheochromocytoma-paraganglioma. | 2 |
| 36346292 | 2023 | High rates of the SDHB p.Arg46Gln pathogenic variant predisposes New Zealand Māori to phaeochromocytoma/paraganglioma. | 0 |
| 36652439 | 2023 | Evidence for a Founder Effect of SDHB Exon 1 Deletion in Brazilian Patients With Paraganglioma. | 1 |
| 36763043 | 2023 | Metabolic Characterization and Glyceraldehyde-3-Phosphate Dehydrogenase-Dependent Regulation of Epithelial Sodium Channels in hPheo1 Wild-type and SDHB Knockdown Cells. | 0 |
| 36786389 | 2023 | Distortion in transmission of pathogenic SDHB- and SDHD-mutated alleles from parent to offspring. | 0 |
| 34906457 | 2022 | Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHB and SDHD. | 3 |
| 35008989 | 2022 | Loss of SDHB Induces a Metabolic Switch in the hPheo1 Cell Line toward Enhanced OXPHOS. | 8 |
| 35300626 | 2022 | Increased expression of Nrf2 and elevated glucose uptake in pheochromocytoma and paraganglioma with SDHB gene mutation. | 3 |
Citation
Anne-Paule Gimenez-Roqueplo
SDHB (succinate dehydrogenase complex II, subunit B, iron-sulfur protein or IP)
Atlas Genet Cytogenet Oncol Haematol. 2002-04-01
Online version: http://atlasgeneticsoncology.org/gene/388
