SDHC succinate dehydrogenase complex, subunit C, integral membrane protein, 15kDa [Homo sapiens (human)] - Gene

Summary

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Official Symbol: SDHCprovided by HGNC
Official Full Name: succinate dehydrogenase complex, subunit C, integral membrane protein, 15kDaprovided by HGNC
Primary source: HGNC:10682
See related: HPRD:03878; MIM:602413
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CYBL; PGL3; QPS1; SDH3; CYB560
Summary: This gene encodes one of four nuclear-encoded subunits that comprise succinate dehydrogenase, also known as mitochondrial complex II, a key enzyme complex of the tricarboxylic acid cycle and aerobic respiratory chains of mitochondria. The encoded protein is one of two integral membrane proteins that anchor other subunits of the complex, which form the catalytic core, to the inner mitochondrial membrane. There are several related pseudogenes for this gene on different chromosomes. Mutations in this gene have been associated with paragangliomas. Alternatively spliced transcript variants have been described. [provided by RefSeq, May 2013]

Genomic context

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Location :: 1q23.3

Sequence :: Chromosome: 1; NC_000001.10 (161284166..161334541)

See SDHC in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

No SDHC mutation were found in patients with sporadic paraganglioma.
Title: Prevalence and spectrum of SDHx mutations in pheochromocytoma and paraganglioma in patients from Belgium: an update.
Tumor DNA mutation screening of the SDHx, VHL, and RET genes and LOH analyses of the SDHx and VHL genes were performed for pheochromocytoma.
Title: Somatic mutation analysis of the SDHB, SDHC, SDHD, and RET genes in the clinical assessment of sporadic and hereditary pheochromocytoma.
Biallelic inactivation of the SDHC gene may represent a new pathway of pathogenesis of syndromic and nonsyndromic renal cell carcinoma, perhaps of both clear cell and papillary histologies
Title: Biallelic inactivation of the SDHC gene in renal carcinoma associated with paraganglioma syndrome type 3.
Case Report: present a 32-year-old man with a familial SDHC mutation who manifests synchronous paragangliomas of the carotid body and the thoracic aortopulmonary window.
Title: Synchronous carotid body and thoracic paraganglioma associated with a germline SDHC mutation.
mammalian cells over expressing mutations in SDHC demonstrate low-dose/low-LET radiation sensitization that is mediated by increased levels of O*- and HO.
Title: Sensitivity to low-dose/low-LET ionizing radiation in mammalian cells harboring mutations in succinate dehydrogenase subunit C is governed by mitochondria-derived reactive oxygen species.
Approximately 15% of all pheochromocytomas or paragangliomas are associated with germline SDH mutation.
Title: Immunohistochemistry for SDHB triages genetic testing of SDHB, SDHC, and SDHD in paraganglioma-pheochromocytoma syndromes.
Observational study of genetic testing. (HuGE Navigator)
Title: Development and validation of a comprehensive mutation and deletion detection assay for SDHB, SDHC, and SDHD.
no clear association was found between gene variants involved in oxygen sensing and chemoresponsiveness, although some mutations in the SDHB and SDHD genes deserve further investigations in a larger population.
Title: A role for succinate dehydrogenase genes in low chemoresponsiveness to hypoxia?
Gene deletions of SDHD and SDHC represent a substantial proportion of all mutations, and must be considered in paraganglioma patients shown to be negative for mutations by sequencing.
Title: Molecular characterization of novel germline deletions affecting SDHD and SDHC in pheochromocytoma and paraganglioma patients.
Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: A role for succinate dehydrogenase genes in low chemoresponsiveness to hypoxia?

Submit: New GeneRIF Correction See all (21)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Gastrointestinal Stromal Tumors

MIM: 606764

Genetic Testing Registry

Paraganglioma and gastric stromal sarcoma

MIM: 606864

Genetic Testing Registry

Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes are characterized by paragangliomas (tumors that arise from neuroendocrine tissues symmetrically distributed along the paravertebral axis from the base of the skull to the pelvis) and by pheochromocytomas (paragangliomas that are confined to the adrenal medulla). Sympathetic paragangliomas hypersecrete catecholamines; parasympathetic paragangliomas are most often nonsecretory. Extra-adrenal parasympathetic paragangliomas are located predominantly in the skull base, neck, and upper medistinum; approximately 95% of such tumors are nonsecretory. In contrast, sympathetic extra-adrenal paragangliomas are generally confined to the lower mediastinum, abdomen, and pelvis, and are typically secretory. Pheochromocytomas, which arise from the adrenal medulla, typically hypersecrete catecholamines. Symptoms of PGL/PCC result either from mass effects or catecholamine hypersecretion (e.g., sustained or paroxysmal elevations in blood pressure, headache, episodic profuse sweating, forceful palpitations, pallor, and apprehension or anxiety). The risk for malignant transformation is greater for extra-adrenal sympathetic paragangliomas than for pheochromocytomas or skull base and neck paragangliomas.

Diagnosis Testing

The diagnosis of hereditary PGL/PCC syndromes is based on physical examination, family history, imaging studies, biochemical testing, and molecular genetic testing. SDHA, SDHB, SDHC and SDHD are four nuclear genes that encode the four subunits of the mitochondrial enzyme succinate dehydrogenase (SDH). A fifth nuclear gene, SDHAF2 (also known as SDH5) encodes a protein that appears to be required for flavination of another SDH subunit, SDHA. These are collectively known as the SDHx genes. Mutations in MAX predispose to PCC; a subset of individuals with mutations in MAX will also develop PGL. KIF1B and EGLN1 (formerly known as PHD2) have been reported to be associated with hereditary PGL/PCC, but their clinical significance is still unclear. Molecular genetic testing for disease-causing variants in SDHA, SDHB, SDHC, SDHD, SDHAF2, and MAX is clinically available.

Genetic Counseling

The hereditary PGL/PCC syndromes are inherited in an autosomal dominant manner. Mutations in SDHD (PGL1) demonstrate parent-of-origin effects and generally cause disease only when the mutation is inherited from the father. Initial data suggest that mutations in SDHAF2 (PGL2) and MAX exhibit parent-of-origin effects similar to those of mutations in SDHD. A proband with a hereditary PGL/PCC syndrome may have inherited the mutation from a parent or have a de novo mutation; the proportion of cases caused by de novo mutations is unknown. Each child of an individual with a hereditary PGL/PCC syndrome has a 50% chance of inheriting the disease-causing mutation. An individual who inherits a SDHD mutation from his/her mother is at a low but not negligible risk of developing disease; each of his/her offspring is at a 50% risk of inheriting the disease-causing allele. An individual who inherits an SDHD mutation from his/her father is at high risk of manifesting paragangliomas and, to a lesser extent, pheochromocytomas. Prenatal testing for pregnancies at increased risk is possible for families in which the disease-causing mutation is known; if no laboratories offering prenatal testing are listed in the GeneTeststrade mark Laboratory Directory, such testing may be available through laboratories offering custom prenatal testing.

References

PMID: 20301715

NHGRI GWAS Catalog

Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
BioGRID:112292	BioGRID:106889	ARHGDIA	BioGRID	PubMed	Two-hybrid
BioGRID:112292	BioGRID:110358	MDM2	BioGRID	PubMed	Two-hybrid
BioGRID:112292	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112292	BioGRID:108822	XRCC6	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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Alzheimer's disease, organism-specific biosystem (from KEGG)
Alzheimer's disease, organism-specific biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
Alzheimer's disease, conserved biosystem (from KEGG)
Alzheimer's disease, conserved biosystemAlzheimer's disease (AD) is a chronic disorder that slowly destroys neurons and causes serious cognitive disability. AD is associated with senile plaques and neurofibrillary tangles (NFTs). Amyloid-b...
Citrate cycle (TCA cycle), organism-specific biosystem (from KEGG)
Citrate cycle (TCA cycle), organism-specific biosystemThe citrate cycle (TCA cycle, Krebs cycle) is an important aerobic pathway for the final steps of the oxidation of carbohydrates and fatty acids. The cycle starts with acetyl-CoA, the activated form ...
Citrate cycle (TCA cycle), conserved biosystem (from KEGG)
Citrate cycle (TCA cycle), conserved biosystemThe citrate cycle (TCA cycle, Krebs cycle) is an important aerobic pathway for the final steps of the oxidation of carbohydrates and fatty acids. The cycle starts with acetyl-CoA, the activated form ...
Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetate, organism-specific biosystem (from KEGG)
Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetate, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Central carbohydrate metabolism
Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetate, conserved biosystem (from KEGG)
Citrate cycle, second carbon oxidation, 2-oxoglutarate => oxaloacetate, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Central carbohydrate metabolism
Citric acid cycle (TCA cycle), organism-specific biosystem (from REACTOME)
Citric acid cycle (TCA cycle), organism-specific biosystemIn the citric acid or tricarboxylic acid (TCA) cycle, the acetyl group of acetyl CoA (derived primarily from oxidative decarboxylation of pyruvate, beta-oxidation of long-chain fatty acids, and catab...
Electron Transport Chain, organism-specific biosystem (from WikiPathways)
Electron Transport Chain, organism-specific biosystemAn electron transport chain(ETC) couples a chemical reaction between an electron donor (such as NADH) and an electron acceptor (such as O2) to the transfer of H+ ions across a membrane, through a set...
Huntington's disease, organism-specific biosystem (from KEGG)
Huntington's disease, organism-specific biosystemHuntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). The symptoms are choreiform, involuntary movements, personality...
Huntington's disease, conserved biosystem (from KEGG)
Huntington's disease, conserved biosystemHuntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). The symptoms are choreiform, involuntary movements, personality...
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Oxidative phosphorylation, organism-specific biosystem (from KEGG)
Oxidative phosphorylation, organism-specific biosystem
Oxidative phosphorylation
Oxidative phosphorylation, conserved biosystem (from KEGG)
Oxidative phosphorylation, conserved biosystem
Oxidative phosphorylation
Parkinson's disease, organism-specific biosystem (from KEGG)
Parkinson's disease, organism-specific biosystemParkinson's disease (PD) is a progressive neurodegenerative movement disorder that results primarily from the death of dopaminergic neurons in the substantia nigra. Mutations in alpha-synuclein, UCHL...
Pyruvate metabolism and Citric Acid (TCA) cycle, organism-specific biosystem (from REACTOME)
Pyruvate metabolism and Citric Acid (TCA) cycle, organism-specific biosystemPyruvate metabolism and the citric acid (TCA) cycle together link the processes of energy metabolism in a human cell with one another and with key biosynthetic reactions. Pyruvate, derived from the r...
Respiratory electron transport, organism-specific biosystem (from REACTOME)
Respiratory electron transport, organism-specific biosystemMitochondria are often described as the "powerhouse" of a cell as it is here that energy is largely released from the oxidation of food. Reducing equivalents generated from beta-oxidation of fatty ac...
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins., organism-specific biosystem (from REACTOME)
Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins., organism-specific biosystemOxidation of fatty acids and pyruvate in the mitochondrial matrix yield large amounts of NADH. The respiratory electron transport chain couples the re-oxidation of this NADH to NAD+ to the export of ...
Succinate dehydrogenase (ubiquinone), organism-specific biosystem (from KEGG)
Succinate dehydrogenase (ubiquinone), organism-specific biosystemStructural complex; Energy metabolism; ATP synthesis
TCA Cycle, organism-specific biosystem (from WikiPathways)
TCA Cycle, organism-specific biosystemThe [[wikipedia:citric_acid_cycle|citric acid cycle]], also known as the tricarboxylic acid cycle (TCA cycle) or the Krebs cycle, (or rarely, the Szent-Gyorgyi-Krebs cycle) is a series of enzyme-cata...
TCA cycle, organism-specific biosystem (from BIOCYC)
TCA cycle, organism-specific biosystem
TCA cycle
TCA cycle II (eukaryotic), conserved biosystem (from BIOCYC)
TCA cycle II (eukaryotic), conserved biosystemGeneral Background The TCA pathway is a catabolic pathway of aerobic respiration that generates both energy and reducing power. In addition, it is also the first step in generating precursors for bi...
The citric acid (TCA) cycle and respiratory electron transport, organism-specific biosystem (from REACTOME)
The citric acid (TCA) cycle and respiratory electron transport, organism-specific biosystemThe metabolism of pyruvate provides one source of acetyl-CoA which enters the citric acid (TCA, tricarboxylic acid) cycle to generate energy and the reducing equivalent NADH. These reducing equivalen...

General gene information

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Markers

WI-11628 (e-PCR)
- UniSTS:4912

AL033654 (e-PCR)
- UniSTS:93489

RH65492 (e-PCR)
- UniSTS:91228

SHGC-31694 (e-PCR)
- UniSTS:25294

Genotypes

Related pseudogene(s)

5 found Review record(s) in Gene

Homology

Homologs of the SDHC gene: The SDHC gene is conserved in Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, and mosquito.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
electron carrier activity	IEA Inferred from Electronic Annotation more info
heme binding	ISS Inferred from Sequence or Structural Similarity more info
metal ion binding	IEA Inferred from Electronic Annotation more info
succinate dehydrogenase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
aerobic respiration	TAS Traceable Author Statement more info	PubMed
oxidation-reduction process	TAS Traceable Author Statement more info	PubMed
respiratory electron transport chain	TAS Traceable Author Statement more info
small molecule metabolic process	TAS Traceable Author Statement more info
tricarboxylic acid cycle	IEA Inferred from Electronic Annotation more info
tricarboxylic acid cycle	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
integral to membrane	TAS Traceable Author Statement more info	PubMed
mitochondrial inner membrane	ISS Inferred from Sequence or Structural Similarity more info
mitochondrial inner membrane	TAS Traceable Author Statement more info
mitochondrial respiratory chain complex II	ISS Inferred from Sequence or Structural Similarity more info
mitochondrion	TAS Traceable Author Statement more info	PubMed
respiratory chain complex II	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: succinate dehydrogenase cytochrome b560 subunit, mitochondrial

Names: succinate dehydrogenase cytochrome b560 subunit, mitochondrial; integral membrane protein CII-3b; succinate dehydrgenase cytochrome b; cytochrome B large subunit of complex II; succinate dehydrogenase 3, integral membrane subunit; succinate-ubiquinone oxidoreductase cytochrome B large subunit

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012767.1 RefSeqGene

Range

5001..55376

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001035511.1 → NP_001030588.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as delta5) lacks an alternate exon in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (2) is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AB211235, AL592295, BG724095, D49737

Consensus CDS

CCDS41431.1

UniProtKB/Swiss-Prot

Q99643

Conserved Domains (1) summary

cd03499
Location:50 – 79
Blast Score: 127

SQR_TypeC_SdhC; Succinate:quinone oxidoreductase (SQR) Type C subfamily, Succinate dehydrogenase C (SdhC) subunit; composed of bacterial SdhC and eukaryotic large cytochrome b binding (CybL) proteins. SQR catalyzes the oxidation of succinate to fumarate coupled to the ...
NM_001035512.1 → NP_001030589.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3, also known as delta3) lacks an alternate exon in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.

Source sequence(s)

AB211234, AL592295, BG724095, D49737

Consensus CDS

CCDS44263.1

UniProtKB/Swiss-Prot

Q99643

Conserved Domains (1) summary

cd03499
Location:19 – 134
Blast Score: 213

SQR_TypeC_SdhC; Succinate:quinone oxidoreductase (SQR) Type C subfamily, Succinate dehydrogenase C (SdhC) subunit; composed of bacterial SdhC and eukaryotic large cytochrome b binding (CybL) proteins. SQR catalyzes the oxidation of succinate to fumarate coupled to the ...
NM_001035513.1 → NP_001030590.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 4 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4, also known as delta2+3) lacks two alternate exons in the 5' coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (4) is shorter than isoform 1.

Source sequence(s)

AB201252, AL592295, BG724095, D49737

Consensus CDS

CCDS41432.1

UniProtKB/Swiss-Prot

Q99643

Conserved Domains (1) summary

cd03499
Location:8 – 99
Blast Score: 189

SQR_TypeC_SdhC; Succinate:quinone oxidoreductase (SQR) Type C subfamily, Succinate dehydrogenase C (SdhC) subunit; composed of bacterial SdhC and eukaryotic large cytochrome b binding (CybL) proteins. SQR catalyzes the oxidation of succinate to fumarate coupled to the ...
NM_001278172.1 → NP_001265101.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 5 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (5, also known as delta 3+5), lacks two alternate exons, which results in a frameshift, compared to variant 1. The encoded isoform (5) is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AB212048, AL592295, BG724095

Conserved Domains (1) summary

cl00881
Location:19 – 45
Blast Score: 89

SQR_QFR_TM; Succinate:quinone oxidoreductase (SQR) and Quinol:fumarate reductase (QFR) family, transmembrane subunits; SQR catalyzes the oxidation of succinate to fumarate coupled to the reduction of quinone to quinol, while QFR catalyzes the reverse reaction. SQR, ...
NM_003001.3 → NP_002992.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AL592295, BC033626, BG724095

Consensus CDS

CCDS1230.1

UniProtKB/Swiss-Prot

Q99643

Conserved Domains (1) summary

cd03499
Location:50 – 168
Blast Score: 265

SQR_TypeC_SdhC; Succinate:quinone oxidoreductase (SQR) Type C subfamily, Succinate dehydrogenase C (SdhC) subunit; composed of bacterial SdhC and eukaryotic large cytochrome b binding (CybL) proteins. SQR catalyzes the oxidation of succinate to fumarate coupled to the ...

RNA

NR_103459.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (6) contains an alternate internal exon, compared to variant 1. This variant is represented as non-coding because use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AL592295, BG724095, DA751501

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000001.10 Reference GRCh37.p10 Primary Assembly

Range

161284166..161334541

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

132641002..132691319

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018912.1 Alternate CHM1_1.0

Range

167780403..167830812

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01016590.1 (22849..39736)	None
genomic	ABBA01016591.1	None
genomic	ABBA01016592.1	None
genomic	AF039594.1	AAC27993.1
genomic	AL592295.25 (38044..88419)	None
genomic	AMYH01001457.1 (262358..312767)	None
genomic	CH471121.2	EAW52597.1
		EAW52598.1
		EAW52599.1
		EAW52600.1
		EAW52601.1
		EAW52602.1
		EAW52603.1
		EAW52604.1
mRNA	AB201252.1	BAE46977.1
mRNA	AB211234.1	BAE46978.1
mRNA	AB211235.1	BAE46979.1
mRNA	AB212048.1	BAE46980.1
mRNA	AK131051.1	None
mRNA	AK293687.1	BAG57126.1
mRNA	AK294305.1	BAG57586.1
mRNA	BC012735.2	None
mRNA	BC020808.1	AAH20808.1
mRNA	BC033626.1	AAH33626.1
mRNA	BC066329.1	AAH66329.1
mRNA	BG724095.1	None
mRNA	CR457102.1	CAG33383.1
mRNA	D49737.1	BAA31998.1
mRNA	DA751501.1	None
mRNA	U57877.1	AAB41838.1