SDHC succinate dehydrogenase complex subunit C [Homo sapiens (human)] - Gene

Summary

Official Symbol: SDHCprovided by HGNC
Official Full Name: succinate dehydrogenase complex subunit Cprovided by HGNC
Primary source: HGNC:HGNC:10682
See related: Ensembl:ENSG00000143252 MIM:602413; AllianceGenome:HGNC:10682
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; PPGL3; 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]
Expression: Ubiquitous expression in kidney (RPKM 80.5), liver (RPKM 66.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q23.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (161314381..161363206)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (160451814..160500650)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (161284171..161332996)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

SDHC Methylation Pattern in Patients With Carney Triad.
Title: SDHC Methylation Pattern in Patients With Carney Triad.
Variant type is associated with disease characteristics in SDHB, SDHC and SDHD-linked phaeochromocytoma-paraganglioma.
Title: Variant type is associated with disease characteristics in SDHB, SDHC and SDHD-linked phaeochromocytoma-paraganglioma.
Low SDHC expression is associated with growth and metastasis of hepatocellular carcinoma.
Title: SDHC-related deficiency of SDH complex activity promotes growth and metastasis of hepatocellular carcinoma via ROS/NFκB signaling.
Specific genotype-tumour risk associations provides a basis for novel investigative strategies into succinate dehydrogenase-related mechanisms of tumourigenesis and the development of personalised management for SDHB/SDHC/SDHD mutation carriers
Title: Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD.
Targeted analysis of DNA methylation array revealed the mesenchymal stem cells in infants born to obese mothers had hypermethylation in genes regulating Fatty Acid Oxidation (PRKAG2, ACC2, CPT1A, SDHC) and corresponding lower mRNA content of these genes. Moreover, mesenchymal stem cells methylation was positively correlated with infant adiposity.
Title: Maternal obesity alters fatty acid oxidation, AMPK activity, and associated DNA methylation in mesenchymal stem cells from human infants.
SDHC Promoter hypermethylation is associated with Parasympathetic Paragangliomas.
Title: SDHC Promoter Methylation, a Novel Pathogenic Mechanism in Parasympathetic Paragangliomas.
SDH-deficient gastrointestinal stromal tumors (GISTs) account for approximately 8% of gastric GISTs and are associated with a high rate of distant metastasis, regardless of conventional risk category.
Title: Conventional Risk Stratification Fails to Predict Progression of Succinate Dehydrogenase-deficient Gastrointestinal Stromal Tumors: A Clinicopathologic Study of 76 Cases.
31% of the paragangliomas in the French Canadian can be explained by the SDHC mutation (c.397C>T, p.[Arg133Ter]).
Title: A SDHC Founder Mutation Causes Paragangliomas (PGLs) in the French Canadians: New Insights on the SDHC-Related PGL.
For classification, tumors were characterized by SDHA, B, C, or D (SDHX) mutations and other genetic and epigenetic alterations, including presence of mutations in germline
Title: Molecular Subtypes of KIT/PDGFRA Wild-Type Gastrointestinal Stromal Tumors: A Report From the National Institutes of Health Gastrointestinal Stromal Tumor Clinic.
Heterozygous germline deletions of up to 104 kb in size were identified in SDHB, SDHC, SDHD and flanking genes in 20 paraganglioma-pheochromocytoma patients. The exact breakpoint could be determined in 16 paraganglioma-pheochromocytoma patients of which 15 were novel deletions
Title: Simple and rapid characterization of novel large germline deletions in SDHB, SDHC and SDHD-related paraganglioma.

Submit: New GeneRIF Correction See all GeneRIFs (45)

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

Professional guidelines

Description
Professional guideline ACMG 2013 The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in SDHC that are pathogenic or expected to be pathogenic. GuidelinePubMed

Associated conditions

Description	Tests
Carney-Stratakis syndrome MedGen: C1847319 OMIM: 606864 GeneReviews: Not available	Compare labs
Gastrointestinal stromal tumor MedGen: C0238198 OMIM: 606764 GeneReviews: Not available	Compare labs
Paragangliomas 3 MedGen: C1854336 OMIM: 605373 GeneReviews: Hereditary Paraganglioma-Pheochromocytoma Syndromes	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2021-10-13) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2021-10-13) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables electron transfer activity	IEA Inferred from Electronic Annotation more info
enables heme binding	ISS Inferred from Sequence or Structural Similarity more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in aerobic respiration	TAS Traceable Author Statement more info	PubMed
involved_in mitochondrial electron transport, succinate to ubiquinone	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitochondrial electron transport, succinate to ubiquinone	NAS Non-traceable Author Statement more info	PubMed
involved_in proton motive force-driven mitochondrial ATP synthesis	NAS Non-traceable Author Statement more info	PubMed
involved_in tricarboxylic acid cycle	IEA Inferred from Electronic Annotation more info
involved_in tricarboxylic acid cycle	NAS Non-traceable Author Statement more info	PubMed
involved_in tricarboxylic acid cycle	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in membrane	TAS Traceable Author Statement more info	PubMed
located_in mitochondrial inner membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in mitochondrial inner membrane	NAS Non-traceable Author Statement more info	PubMed
located_in mitochondrial inner membrane	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
located_in mitochondrion	TAS Traceable Author Statement more info	PubMed
part_of respiratory chain complex II (succinate dehydrogenase)	IBA Inferred from Biological aspect of Ancestor more info
part_of respiratory chain complex II (succinate dehydrogenase)	IDA Inferred from Direct Assay more info	PubMed
part_of respiratory chain complex II (succinate dehydrogenase)	ISS Inferred from Sequence or Structural Similarity more info
part_of respiratory chain complex II (succinate dehydrogenase)	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: succinate dehydrogenase cytochrome b560 subunit, mitochondrial

Names: cytochrome B large subunit of complex II; integral membrane protein CII-3b; large subunit of cytochrome b; malate dehydrogenase [quinone] cytochrome b560 subunit; succinate dehydrgenase cytochrome b; succinate dehydrogenase 3, integral membrane subunit; succinate dehydrogenase complex subunit C integral membrane protein 15kDa; succinate dehydrogenase complex, subunit C, integral membrane protein, 15kD; 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), LRG_317

mRNA and Protein(s)

NM_001035511.3 → NP_001030588.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 2 precursor

See identical proteins and their annotated locations for NP_001030588.1

Status: REVIEWED

Source sequence(s)

AL592295

Consensus CDS

CCDS41431.1

UniProtKB/Swiss-Prot

Q99643

Related

ENSP00000356952.3, ENST00000342751.8

Conserved Domains (1) summary

cl00881
Location:50 → 79

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_001035512.3 → NP_001030589.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 3 precursor

See identical proteins and their annotated locations for NP_001030589.1

Status: REVIEWED

Source sequence(s)

AL592295

Consensus CDS

CCDS44263.1

UniProtKB/TrEMBL

B4DEL5

Related

ENSP00000390558.2, ENST00000432287.6

Conserved Domains (1) summary

cd03499
Location:19 → 118

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_001035513.3 → NP_001030590.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 4 precursor

See identical proteins and their annotated locations for NP_001030590.1

Status: REVIEWED

Source sequence(s)

AL592295

Consensus CDS

CCDS41432.1

UniProtKB/TrEMBL

A0A0S2Z4C9, B4DEL5

Related

ENSP00000376009.2, ENST00000392169.6

Conserved Domains (1) summary

cd03499
Location:8 → 115

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_001278172.3 → NP_001265101.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 5 precursor

See identical proteins and their annotated locations for NP_001265101.1

Status: REVIEWED

Source sequence(s)

AL592295

Consensus CDS

CCDS60330.1

UniProtKB/TrEMBL

A0AAQ5BH99

Related

ENSP00000423260.1, ENST00000513009.5

Conserved Domains (1) summary

cl00881
Location:19 → 45

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_001407115.1 → NP_001394044.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 6 precursor

Status: REVIEWED

Source sequence(s)

AL592295
NM_001407116.1 → NP_001394045.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 7 precursor

Status: REVIEWED

Source sequence(s)

AL592295
NM_001407117.1 → NP_001394046.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 8 precursor

Status: REVIEWED

Source sequence(s)

AL592295
NM_001407118.1 → NP_001394047.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 9 precursor

Status: REVIEWED

Source sequence(s)

AL592295
NM_001407119.1 → NP_001394048.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 10

Status: REVIEWED

Source sequence(s)

AL592295

UniProtKB/TrEMBL

A0AAQ5BHE7

Related

ENSP00000519356.1, ENST00000714065.1
NM_001407120.1 → NP_001394049.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 10

Status: REVIEWED

Source sequence(s)

AL592295

UniProtKB/TrEMBL

A0AAQ5BHE7

Related

ENSP00000519355.1, ENST00000714064.1
NM_001407121.1 → NP_001394050.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 11 precursor

Status: REVIEWED

Source sequence(s)

AL592295

Related

ENSP00000519353.1, ENST00000515731.2
NM_003001.5 → NP_002992.1 succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_002992.1

Status: REVIEWED

Source sequence(s)

AL592295

Consensus CDS

CCDS1230.1

UniProtKB/Swiss-Prot

O75609, Q3C259, Q3C2D8, Q3C2H4, Q5VTH3, Q99643

UniProtKB/TrEMBL

A0A0S2Z4B7, Q6IAQ2

Related

ENSP00000356953.3, ENST00000367975.7

Conserved Domains (1) summary

cd03499
Location:50 → 152

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 ...