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
SDHD
LOCATION
11q23.1
LOCUSID
6392
ALIAS
CBT1,CII-4,CWS3,MC2DN3,PGL,PGL1,QPs3,SDH4,cybS
FUSION GENES
Show Gene Fusions

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.

Article 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
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

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
cerebral cortex
cerebellum
hippocampus
caudate
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA165543618SDHAF2GeneDataAnnotationassociated
PA35606SDHBGeneDataAnnotationassociated
PA35607SDHCGeneDataAnnotationassociated
PA445229ParagangliomaDiseaseDataAnnotationassociated
PA445315PheochromocytomaDiseaseDataAnnotationassociated

References

Pubmed IDYearTitleCitations
362230422023A need to tailor surveillance based on family history: describing a highly penetrant familial paraganglioma kindred with an SDHD pathogenic variant.0
367863892023Distortion in transmission of pathogenic SDHB- and SDHD-mutated alleles from parent to offspring.0
370116472023Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants.11
362230422023A need to tailor surveillance based on family history: describing a highly penetrant familial paraganglioma kindred with an SDHD pathogenic variant.0
367863892023Distortion in transmission of pathogenic SDHB- and SDHD-mutated alleles from parent to offspring.0
370116472023Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants.11
332191052022Characteristics of germline mutations in Korean patients with pheochromocytoma/paraganglioma.3
348082252022MicroRNA-101-3p Modulates Mitochondrial Metabolism via the Regulation of Complex II Assembly.7
349064572022Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHB and SDHD.3
366140702022The SDHD:p.H102R Variant Is Frequent in Russian Patients with Head and Neck Paragangliomas and Associated with Loss of 11p15.5 Region and Hypermethylation of H19-DMR.1
332191052022Characteristics of germline mutations in Korean patients with pheochromocytoma/paraganglioma.3
348082252022MicroRNA-101-3p Modulates Mitochondrial Metabolism via the Regulation of Complex II Assembly.7
349064572022Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHB and SDHD.3
366140702022The SDHD:p.H102R Variant Is Frequent in Russian Patients with Head and Neck Paragangliomas and Associated with Loss of 11p15.5 Region and Hypermethylation of H19-DMR.1
336497942021Bcl2l10 induces metabolic alterations in ovarian cancer cells by regulating the TCA cycle enzymes SDHD and IDH1.3

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