SDHB (succinate dehydrogenase complex II, subunit B, iron-sulfur protein or IP)

2002-04-01   Anne-Paule Gimenez-Roqueplo 

Département de Génétique Moléculaire, Hôpital Européen Georges Pompidou, 20-40, rue Leblanc, 75908 Paris cedex 15, France

Identity

HGNC
LOCATION
1p36.13
IMAGE
Atlas 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.

Homology

The complex II includes SDHD (cybS) and SDHC (cybL) which are also implicated in paragangliomas and pheochromocytomas.

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.

Bibliography

Pubmed IDLast YearTitleAuthors
114048202001Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma.Astuti D et al
76220591995Structural organization of the gene encoding the human iron-sulfur subunit of succinate dehydrogenase.Au HC et al
118978172002Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas.Baysal BE et al
173795202007RASSF1A is part of a complex similar to the Drosophila Hippo/Salvador/Lats tumor-suppressor network.Guo C et al
82910261993The 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 IDTranscript IDUniprot
ENSG00000117118ENST00000375499P21912
ENSG00000117118ENST00000463045A0A087WXX8
ENSG00000117118ENST00000491274A0A087WWT1

Expression (GTEx)

0
50
100
150
200

Pathways

PathwaySourceExternal ID
Citrate cycle (TCA cycle)KEGGko00020
Oxidative phosphorylationKEGGko00190
Alzheimer's diseaseKEGGko05010
Huntington's diseaseKEGGko05016
Citrate cycle (TCA cycle)KEGGhsa00020
Oxidative phosphorylationKEGGhsa00190
Alzheimer's diseaseKEGGhsa05010
Parkinson's diseaseKEGGhsa05012
Huntington's diseaseKEGGhsa05016
Metabolic pathwaysKEGGhsa01100
Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetateKEGGhsa_M00011
Succinate dehydrogenase (ubiquinone)KEGGhsa_M00148
Citrate cycle (TCA cycle, Krebs cycle)KEGGM00009
Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetateKEGGM00011
Carbon metabolismKEGGhsa01200
Carbon metabolismKEGGko01200
Citrate cycle (TCA cycle, Krebs cycle)KEGGhsa_M00009
Non-alcoholic fatty liver disease (NAFLD)KEGGhsa04932
Non-alcoholic fatty liver disease (NAFLD)KEGGko04932
Succinate dehydrogenase (ubiquinone)KEGGM00148
MetabolismREACTOMER-HSA-1430728
The citric acid (TCA) cycle and respiratory electron transportREACTOMER-HSA-1428517
Pyruvate metabolism and Citric Acid (TCA) cycleREACTOMER-HSA-71406
Citric acid cycle (TCA cycle)REACTOMER-HSA-71403
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.REACTOMER-HSA-163200
Respiratory electron transportREACTOMER-HSA-611105

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA165543618SDHAF2GeneDataAnnotationassociated
PA35607SDHCGeneDataAnnotationassociated
PA35608SDHDGeneDataAnnotationassociated
PA445229ParagangliomaDiseaseDataAnnotationassociated
PA445315PheochromocytomaDiseaseDataAnnotationassociated

References

Pubmed IDYearTitleCitations
226775462012Inhibition of α-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors.274
120008162002Germ-line mutations in nonsyndromic pheochromocytoma.224
153283262004Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations.184
211732202011Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations.159
179678652008Loss of the SdhB, but Not the SdhA, subunit of complex II triggers reactive oxygen species-dependent hypoxia-inducible factor activation and tumorigenesis.141
163146412005Genetic testing in pheochromocytoma or functional paraganglioma.129
176679672008Clinical 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.106
187282832008Germline SDHB mutations and familial renal cell carcinoma.106
187282832008Germline SDHB mutations and familial renal cell carcinoma.106
146859382004Early-onset renal cell carcinoma as a novel extraparaganglial component of SDHB-associated heritable paraganglioma.102

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/sdhb