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

2002-02-01 Anne-Paule Gimenez-Roqueplo Affiliation

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 ID	Last Year	Title	Authors
11323050	2001	Germline SDHD mutation in familial phaeochromocytoma.	Astuti D et al
10657297	2000	Mutations in SDHD, a mitochondrial complex II gene, in hereditary paraganglioma.	Baysal BE et al
11313745	2001	A 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
11605159	2001	The 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
11156372	2000	Somatic and occult germ-line mutations in SDHD, a mitochondrial complex II gene, in nonfamilial pheochromocytoma.	Gimm O et al
10482792	1999	Characterization of the human SDHD gene encoding the small subunit of cytochrome b (cybS) in mitochondrial succinate-ubiquinone oxidoreductase.	Hirawake H et al
11343322	2001	Novel mutations and the emergence of a common mutation in the SDHD gene causing familial paraganglioma.	Milunsky JM et al
11391798	2001	Nearly 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 ID	Transcript ID	Uniprot
ENSG00000204370	ENST00000375549	O14521
ENSG00000204370	ENST00000375549	A0A0S2Z4J3
ENSG00000204370	ENST00000525291	O14521
ENSG00000204370	ENST00000526592	O14521
ENSG00000204370	ENST00000528021	G3V173
ENSG00000204370	ENST00000528048	O14521
ENSG00000204370	ENST00000528048	A0A0S2Z4H7
ENSG00000204370	ENST00000528182	E9PK73
ENSG00000204370	ENST00000530923	H0YD41
ENSG00000204370	ENST00000534010	H0YD96
ENSG00000204370	ENST00000614349	O14521
ENSG00000204370	ENST00000640554	A0A1W2PNY0

Expression (GTEx)

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

Pathway	Source	External ID
Citrate cycle (TCA cycle)	KEGG	ko00020
Oxidative phosphorylation	KEGG	ko00190
Alzheimer's disease	KEGG	ko05010
Huntington's disease	KEGG	ko05016
Citrate cycle (TCA cycle)	KEGG	hsa00020
Oxidative phosphorylation	KEGG	hsa00190
Alzheimer's disease	KEGG	hsa05010
Parkinson's disease	KEGG	hsa05012
Huntington's disease	KEGG	hsa05016
Metabolic pathways	KEGG	hsa01100
Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetate	KEGG	hsa_M00011
Succinate dehydrogenase (ubiquinone)	KEGG	hsa_M00148
Citrate cycle (TCA cycle, Krebs cycle)	KEGG	M00009
Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetate	KEGG	M00011
Carbon metabolism	KEGG	hsa01200
Carbon metabolism	KEGG	ko01200
Citrate cycle (TCA cycle, Krebs cycle)	KEGG	hsa_M00009
Non-alcoholic fatty liver disease (NAFLD)	KEGG	hsa04932
Non-alcoholic fatty liver disease (NAFLD)	KEGG	ko04932
Succinate dehydrogenase (ubiquinone)	KEGG	M00148
Metabolism	REACTOME	R-HSA-1430728
The citric acid (TCA) cycle and respiratory electron transport	REACTOME	R-HSA-1428517
Pyruvate metabolism and Citric Acid (TCA) cycle	REACTOME	R-HSA-71406
Citric acid cycle (TCA cycle)	REACTOME	R-HSA-71403
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.	REACTOME	R-HSA-163200
Respiratory electron transport	REACTOME	R-HSA-611105

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association
PA165543618	SDHAF2	Gene	DataAnnotation	associated
PA35606	SDHB	Gene	DataAnnotation	associated
PA35607	SDHC	Gene	DataAnnotation	associated
PA445229	Paraganglioma	Disease	DataAnnotation	associated
PA445315	Pheochromocytoma	Disease	DataAnnotation	associated

References

Pubmed ID	Year	Title	Citations
36223042	2023	A need to tailor surveillance based on family history: describing a highly penetrant familial paraganglioma kindred with an SDHD pathogenic variant.	0
36786389	2023	Distortion in transmission of pathogenic SDHB- and SDHD-mutated alleles from parent to offspring.	0
37011647	2023	Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants.	11
36223042	2023	A need to tailor surveillance based on family history: describing a highly penetrant familial paraganglioma kindred with an SDHD pathogenic variant.	0
36786389	2023	Distortion in transmission of pathogenic SDHB- and SDHD-mutated alleles from parent to offspring.	0
37011647	2023	Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants.	11
33219105	2022	Characteristics of germline mutations in Korean patients with pheochromocytoma/paraganglioma.	3
34808225	2022	MicroRNA-101-3p Modulates Mitochondrial Metabolism via the Regulation of Complex II Assembly.	7
34906457	2022	Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHB and SDHD.	3
36614070	2022	The 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
33219105	2022	Characteristics of germline mutations in Korean patients with pheochromocytoma/paraganglioma.	3
34808225	2022	MicroRNA-101-3p Modulates Mitochondrial Metabolism via the Regulation of Complex II Assembly.	7
34906457	2022	Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHB and SDHD.	3
36614070	2022	The 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
33649794	2021	Bcl2l10 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/deep-insight-explorer/favicon/css/lib/dataTables.bootstrap.min.css