SDHD (succinate dehydrogenase complex II, subunit D, integral membrane protein)

2002-02-01   Anne-Paule Gimenez-Roqueplo 

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

Identity

HGNC
LOCATION
11q23.1
LOCUSID
ALIAS
CBT1,CII-4,CWS3,MC2DN3,PGL,PGL1,QPs3,SDH4,cybS
FUSION GENES

DNA/RNA

Description

8895 bp, 4 exons

Transcription

A non transcribed sequence highly homologous to SDHD cDNA is present on chromosome 1p36-p34

Proteins

Description

159 amino acids and 17 kDa

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 D protein or small subunit (cybS) is one of two integral membrane proteins anchoring the complex to membrane.

Homology

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

Mutations

Germinal

Germline mutations cause hereditary paraganglioma. Different types of mutations are described. False-sense mutations, insertions and deletions leading to protein truncation and missense mutations.

Somatic

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

Implicated in

Entity name
Hereditary paraganglioma type 1 (also called familial non chromaffin paragangliomas 1, or familial glomus tumor)
Disease
Hereditary paraganglioma type 1 (PGL1) is a rare autosomal dominant disorder. The disease is transmitted through fathers and no disease phenotype is transmetted maternally in accordance with a maternal genomic imprinting. 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). They may be associated with pheochromocytomas.
Prognosis
It depends on extent of the disease at the time of diagnosis.

Bibliography

Pubmed IDLast YearTitleAuthors
113230502001Germline SDHD mutation in familial phaeochromocytoma.Astuti D et al
106572972000Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.Baysal BE et al
113137452001A high-resolution integrated map spanning the SDHD gene at 11q23: a 1.1-Mb BAC contig, a partial transcript map and 15 new repeat polymorphisms in a tumour-suppressor region.Baysal BE et al
116051592001The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway.Gimenez-Roqueplo AP et al
111563722000Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma.Gimm O et al
104827921999Characterization of the human SDHD gene encoding the small subunit of cytochrome b (cybS) in mitochondrial succinate-ubiquinone oxidoreductase.Hirawake H et al
113433222001Novel mutations and the emergence of a common mutation in the SDHD gene causing familial paraganglioma.Milunsky JM et al
113917982001Nearly all hereditary paragangliomas in the Netherlands are caused by two founder mutations in the SDHD gene.Taschner PE et al

Other Information

Locus ID:

NCBI: 6392
MIM: 602690
HGNC: 10683
Ensembl: ENSG00000204370

Variants:

dbSNP: 6392
ClinVar: 6392
TCGA: ENSG00000204370
COSMIC: SDHD

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000204370ENST00000375549O14521
ENSG00000204370ENST00000375549A0A0S2Z4J3
ENSG00000204370ENST00000525291O14521
ENSG00000204370ENST00000526592O14521
ENSG00000204370ENST00000528021G3V173
ENSG00000204370ENST00000528048O14521
ENSG00000204370ENST00000528048A0A0S2Z4H7
ENSG00000204370ENST00000528182E9PK73
ENSG00000204370ENST00000530923H0YD41
ENSG00000204370ENST00000534010H0YD96
ENSG00000204370ENST00000614349O14521
ENSG00000204370ENST00000640554A0A1W2PNY0

Expression (GTEx)

0
10
20
30
40
50
60
70
80
90
100

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
PA35606SDHBGeneDataAnnotationassociated
PA35607SDHCGeneDataAnnotationassociated
PA445229ParagangliomaDiseaseDataAnnotationassociated
PA445315PheochromocytomaDiseaseDataAnnotationassociated

References

Pubmed IDYearTitleCitations
120008162002Germ-line mutations in nonsyndromic pheochromocytoma.224
153283262004Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations.184
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
198028982010Tumor risks and genotype-phenotype-proteotype analysis in 358 patients with germline mutations in SDHB and SDHD.90
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
116051592001The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway.76
192400612009Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.75
126126542003A role for mitochondrial enzymes in inherited neoplasia and beyond.72

Citation

Anne-Paule Gimenez-Roqueplo

SDHD (succinate dehydrogenase complex II, subunit D, integral membrane protein)

Atlas Genet Cytogenet Oncol Haematol. 2002-02-01

Online version: http://atlasgeneticsoncology.org/gene/390/sdhd