SDHC (succinate dehydrogenase complex II, subunit C, integral membrane protein)

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
1q23.3
LOCUSID
ALIAS
CYB560,CYBL,PGL3,QPS1,SDH3
FUSION GENES

DNA/RNA

Description

1180 bp, 6 exons

Proteins

Expression

widely expressed

Localisation

mitochondrial inner membrane

Function

Complex II (succinate-ubiquinone oxidoreductase) of the respiratory chain is involved in the oxidation of succinate, carries electrons from FADH to CoQ. It is composed of four nuclear-encoded subunits. The subunit C protein or large subunit (cybL) is one of two integral membrane proteins anchoring the complex to membrane.

Homology

The complex II includes SDHD (cybS) and SDHB (iron-sulfur protein) which are also implicated in paragangliomas and pheochromocytomas.

Mutations

Germinal

Germline mutations cause hereditary paraganglioma. At this time, an unique mutation which destroyed the initial site of traduction (ATG, start codon) of SDHC gene has been reported in a family with a hereditary paraganglioma.

Somatic

Loss of wild type allele in tumor DNA is usually observed.

Implicated in

Entity name
Hereditary paraganglioma type 3
Note
Alias: Familial non chromaffin paragangliomas 3; Familial glomus tumor
Disease
Hereditary paraganglioma type 3 (PGL3) is a rare autosomal dominant disorder non maternally imprinted. Paragangliomas are slow growing highly vascular tumor, usually benign, derived from crest-neural cells. They are preferentially located in the neck (carotid body and glomus vagal) and head (glomus jugulare and tympanicum).
Prognosis
It depends on extent of the disease at the time of diagnosis.

Bibliography

Pubmed IDLast YearTitleAuthors
118978172002Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas.Baysal BE et al
97146071998Characterization of the human SDHC gene encoding of the integral membrane proteins of succinate-quinone oxidoreductase in mitochondria.Elbehti-Green A et al
95330301997Cytochrome b in human complex II (succinate-ubiquinone oxidoreductase): cDNA cloning of the components in liver mitochondria and chromosome assignment of the genes for the large (SDHC) and small (SDHD) subunits to 1q21 and 11q23.Hirawake H et al
114264532001Assignment of PGL3 to chromosome 1 (q21-q23) in a family with autosomal dominant non-chromaffin paraganglioma.Niemann S et al
110624602000Mutations in SDHC cause autosomal dominant paraganglioma, type 3.Niemann S et al

Other Information

Locus ID:

NCBI: 6391
MIM: 602413
HGNC: 10682
Ensembl: ENSG00000143252

Variants:

dbSNP: 6391
ClinVar: 6391
TCGA: ENSG00000143252
COSMIC: SDHC

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000143252ENST00000342751Q99643
ENSG00000143252ENST00000367975Q99643
ENSG00000143252ENST00000367975A0A0S2Z4B7
ENSG00000143252ENST00000392169Q99643
ENSG00000143252ENST00000392169A0A0S2Z4C9
ENSG00000143252ENST00000432287Q99643
ENSG00000143252ENST00000470743A0A087WZU7
ENSG00000143252ENST00000504963D6RBX6
ENSG00000143252ENST00000513009Q99643

Expression (GTEx)

0
5
10
15
20
25

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

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA165543618SDHAF2GeneDataAnnotationassociated
PA35606SDHBGeneDataAnnotationassociated
PA35608SDHDGeneDataAnnotationassociated
PA445229ParagangliomaDiseaseDataAnnotationassociated
PA445315PheochromocytomaDiseaseDataAnnotationassociated

References

Pubmed IDYearTitleCitations
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
126126542003A role for mitochondrial enzymes in inherited neoplasia and beyond.72
118978172002Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas.71
118978172002Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas.71
270110362016Molecular Subtypes of KIT/PDGFRA Wild-Type Gastrointestinal Stromal Tumors: A Report From the National Institutes of Health Gastrointestinal Stromal Tumor Clinic.66
156652962005A mutation in the SDHC gene of complex II increases oxidative stress, resulting in apoptosis and tumorigenesis.65
202366882010Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes.64
192235162009Clinically guided genetic screening in a large cohort of italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas.55
178048572007Familial gastrointestinal stromal tumors and germ-line mutations.54

Citation

Anne-Paule Gimenez-Roqueplo

SDHC (succinate dehydrogenase complex II, subunit C, integral membrane protein)

Atlas Genet Cytogenet Oncol Haematol. 2002-04-01

Online version: http://atlasgeneticsoncology.org/gene/389/sdhc-(succinate-dehydrogenase-complex-ii-subunit-c-integral-membrane-protein)