SDHC

Summary

SDHC (succinate dehydrogenase complex subunit C, HGNC:10682) is a protein-coding gene on chromosome 1q23.3, encoding Succinate dehydrogenase cytochrome b560 subunit, mitochondrial (Q99643). Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). It is a common-essential gene (DepMap: required in 92.0% of cancer cell lines) and haploinsufficient (ClinGen: sufficient evidence).

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.

Source: NCBI Gene 6391 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary pheochromocytoma-paraganglioma (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 1,010 total — 69 pathogenic, 32 likely-pathogenic
• Phenotypes (HPO): 144
• Cancer dependency (DepMap): dependent in 92.0% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_003001

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10682
Approved symbol	SDHC
Name	succinate dehydrogenase complex subunit C
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	CYB560, cybL
Ensembl gene	ENSG00000143252
Ensembl biotype	protein_coding
OMIM	602413
Entrez	6391

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 2 nonsense_mediated_decay

ENST00000342751, ENST00000367975, ENST00000392169, ENST00000432287, ENST00000470743, ENST00000504963, ENST00000513009, ENST00000515731, ENST00000714063, ENST00000714064, ENST00000714065, ENST00000714066, ENST00000893929, ENST00000893930, ENST00000893931

RefSeq mRNA: 12 — MANE Select: NM_003001 NM_001035511, NM_001035512, NM_001035513, NM_001278172, NM_001407115, NM_001407116, NM_001407117, NM_001407118, NM_001407119, NM_001407120, NM_001407121, NM_003001

CCDS: CCDS1230, CCDS41431, CCDS41432, CCDS44263, CCDS60330

Canonical transcript exons

ENST00000367975 — 6 exons

Exon	Start	End
ENSE00001931697	161362329	161363206
ENSE00003505683	161323614	161323670
ENSE00003545898	161328396	161328497
ENSE00003689529	161340594	161340655
ENSE00003901936	161314381	161314425
ENSE00004022699	161356677	161356840

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 65.4202 / max 409.0594, expressed in 1823 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6241	65.4202	1823

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	98.82	gold quality
right adrenal gland cortex	UBERON:0035827	98.72	gold quality
right adrenal gland	UBERON:0001233	98.71	gold quality
adult mammalian kidney	UBERON:0000082	98.48	gold quality
left adrenal gland	UBERON:0001234	98.48	gold quality
left adrenal gland cortex	UBERON:0035825	98.35	gold quality
rectum	UBERON:0001052	98.21	gold quality
adrenal gland	UBERON:0002369	98.19	gold quality
smooth muscle tissue	UBERON:0001135	98.06	gold quality
duodenum	UBERON:0002114	98.06	gold quality
heart left ventricle	UBERON:0002084	98.01	gold quality
right lobe of liver	UBERON:0001114	97.88	gold quality
gastrocnemius	UBERON:0001388	97.84	gold quality
mucosa of transverse colon	UBERON:0004991	97.83	gold quality
liver	UBERON:0002107	97.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.61	gold quality
esophagus mucosa	UBERON:0002469	97.59	gold quality
monocyte	CL:0000576	97.58	gold quality
apex of heart	UBERON:0002098	97.55	gold quality
heart	UBERON:0000948	97.53	gold quality
leukocyte	CL:0000738	97.48	gold quality
kidney	UBERON:0002113	97.40	gold quality
right atrium auricular region	UBERON:0006631	97.39	gold quality
muscle of leg	UBERON:0001383	97.36	gold quality
endometrium	UBERON:0001295	97.35	gold quality
skeletal muscle tissue	UBERON:0001134	97.21	gold quality
metanephros cortex	UBERON:0010533	97.20	gold quality
esophagus	UBERON:0001043	97.19	gold quality
substantia nigra	UBERON:0002038	97.19	gold quality
colonic epithelium	UBERON:0000397	97.17	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.48
E-GEOD-36552	no	79.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR2, NFKBIB, NFYA

miRNA regulators (miRDB)

100 targeting SDHC, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4428	99.73	66.41	1733

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 92.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Prevalence of SDHB, SDHC, and SDHD germline mutations in clinic patients with head and neck paragangliomas (PMID:11897817)
• Review. Succinate dehydrogenase catalyses a step in the Krebs tricarboxylic-acid cycle. Inherited heterozygous mutations in the gene encoding this enzyme causes a predisposition to inherited neoplasia syndromes. (PMID:12612654)
• A splice donor site mutation in SDHC is associates with autosomal dominant malignant and catecholamine-producing paraganglioma (PMID:12658451)
• description of a large deletion in a complex II gene and confirmation of the role of SDHC in familial and sporadic paragangliomas (PMID:15342702)
• Mutant protein in transgenic mice generates oxidative stress and can contribute to nuclear DNA damage, mutagenesis, and ultimately, tumorigenesis (PMID:15665296)
• A possible role for SDH polymorphism as susceptibility/disease modifying factors in familial and sporadic medullary thyroid carcinomas was shown. (PMID:16322339)
• Germline mutations of SDHC play a minor role in sporadic head and neck paraganglioma. (PMID:16405730)
• investigated 11 patients with the dyad of ‘paraganglioma and gastric stromal sarcoma’; in eight, from 7 unrelated families, the GISTs were caused by germline mutations of the genes encoding subunits B, C, or D (the SDHB, SDHC and SDHD genes, respectively) (PMID:17667967)
• familial gastrointestinal stromal tumors may be caused by mutations of the succinate dehydrogenase subunit genes SDHB, SDHC, and SDHD, and abdominal paragangliomas associated with gastrointestinal tumors may be caused uniquely by SDHC mutations (PMID:17804857)
• 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. (PMID:19546167)
• 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. (PMID:19768395)
• Approximately 15% of all pheochromocytomas or paragangliomas are associated with germline SDH mutation. (PMID:20236688)
• 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. (PMID:21106325)
• mammalian cells over expressing mutations in SDHC demonstrate low-dose/low-LET radiation sensitization that is mediated by increased levels of O*- and HO. (PMID:21268708)
• 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 (PMID:22351710)
• No SDHC mutation were found in patients with sporadic paraganglioma. (PMID:22566194)
• Tumor DNA mutation screening of the SDHx, VHL, and RET genes and LOH analyses of the SDHx and VHL genes were performed for pheochromocytoma. (PMID:22573489)
• Studies indicate that an array of tumor syndromes caused by complex II-associated mutations in genes SDHA, SDHB, SDHC, SDHD, SDHAF1 and SDHAF2 have been identified over a decade. (PMID:23174333)
• Overall, 9 of the 34 patients with KIT/PDGFRA wild-type GIST carried mutations in one of the four subunits of the SDH complex (six patients in SDHA, two in SDHB, one in SDHC (PMID:23612575)
• SDH deficiency may promote tumorigenesis through accumulation of succinate and inhibition of dioxygenase enzymes. Inhibition of TET activity may, in turn, alter global DNA methylation and gene expression in SDH-deficient tumors. (PMID:23743927)
• this study reports the first patient affected by malignant paraganglioma and< moreover, it reports two more unrelated patients with the same genotype and very different clinical presentations. (PMID:24423348)
• Thoracic paragangliomas are common in patients with SDHC mutations, and imaging of this area should be included in surveillance of mutation carriers. (PMID:24758179)
• these data suggest epigenetic inactivation of the SDHC gene locus with functional impairment of the SDHC as a plausible alternate mechanism of tumorigenesis in Carney Triad (PMID:24859990)
• Variant in rs3935401 in the 3’ untranslated region of SDHC is associated with hepatocellular carcinoma. (PMID:25081338)
• The discovery of SDHC epimutation provides a unifying explanation for the pathogenesis of SDH-deficient gastrointestinal stromal tumors. (PMID:25540324)
• Both germline and somatic SDHx mutations/variants occur in sporadic differentiated thyroid cancer (DTC) but are very rare in sporadic breast cancer, and overall loss of SDHx gene expression is a signature of DTC (PMID:25694510)
• Loss of the SDHC gene is associated with metastatic sympathetic paraganglioma. (PMID:26162468)
• This study strengthens the etiological association of SDH genes with pituitary neoplasia, renal tumorigenesis, and gastric gastrointestinal stromal tumors. Also, pancreatic neuroendocrine tumor falls within the SDH-related tumor spectrum. (PMID:26259135)
• significant association with overall survival were confirmed for SDHC gene, SDHD gene and FH gene … SDHC gene and FH gene were the primary factors contributing to the different overall survival time of colorectal carcinoma (PMID:26377099)
• According to international guidelines, SDHB, SDHC, and SDHD genetic testing were performed in this patient, but not SDHA, which would have been prescribed only after surgery, in case of SDHA negative immunohistochemistry (PMID:26490314)
• This report provides evidence that SDHC promoter methylation can cause Paragangliomas due to SDHC inactivation (PMID:26652933)
• 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 (PMID:27011036)
• 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. (PMID:27340750)
• 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 (PMID:27485256)
• 31% of the paragangliomas in the French Canadian can be explained by the SDHC mutation (c.397C>T, p.[Arg133Ter]). (PMID:27700540)
• 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. (PMID:29107296)
• SDHC Promoter hypermethylation is associated with Parasympathetic Paragangliomas. (PMID:29126304)
• 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 (PMID:29386252)
• Low SDHC expression is associated with growth and metastasis of hepatocellular carcinoma. (PMID:31278950)
• Variant type is associated with disease characteristics in SDHB, SDHC and SDHD-linked phaeochromocytoma-paraganglioma. (PMID:31492822)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sdhc	ENSDARG00000038608
mus_musculus	Sdhc	ENSMUSG00000058076
rattus_norvegicus	Sdhc	ENSRNOG00000003163
drosophila_melanogaster	SdhCL	FBGN0037860
caenorhabditis_elegans		WBGENE00003225

Protein

Protein identifiers

Succinate dehydrogenase cytochrome b560 subunit, mitochondrial — Q99643 (reviewed: Q99643)

Alternative names: Integral membrane protein CII-3, Malate dehydrogenase [quinone] cytochrome b560 subunit, QPs-1, Succinate dehydrogenase complex subunit C, Succinate-ubiquinone oxidoreductase cytochrome B large subunit

All UniProt accessions (8): Q99643, A0A087WZU7, A0A0S2Z4B7, A0A0S2Z4C9, A0AAQ5BH99, A0AAQ5BHB5, A0AAQ5BHE7, D6RBX6

UniProt curated annotations — full annotation on UniProt →

Function. Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). SDH also oxidizes malate to the non-canonical enol form of oxaloacetate, enol-oxaloacetate. Enol-oxaloacetate, which is a potent inhibitor of the succinate dehydrogenase activity, is further isomerized into keto-oxaloacetate.

Subunit / interactions. Component of complex II composed of four subunits: the flavoprotein (FP) SDHA, iron-sulfur protein (IP) SDHB, and a cytochrome b560 composed of SDHC and SDHD.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. Pheochromocytoma/paraganglioma syndrome 3 (PPGL3) [MIM:605373] A form of pheochromocytoma/paraganglioma syndrome, a tumor predisposition syndrome characterized by the development of neuroendocrine tumors, usually in adulthood. Pheochromocytomas are catecholamine-producing tumors that arise from chromaffin cells in the adrenal medulla. Paragangliomas develop from sympathetic paraganglia in the thorax, abdomen, and pelvis, as well as from parasympathetic paraganglia in the head and neck. PPGL3 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Paraganglioma and gastric stromal sarcoma (PGGSS) [MIM:606864] Gastrointestinal stromal tumors may be sporadic or inherited in an autosomal dominant manner, alone or as a component of a syndrome associated with other tumors, such as in the context of neurofibromatosis type 1 (NF1). Patients have both gastrointestinal stromal tumors and paragangliomas. Susceptibility to the tumors was inherited in an apparently autosomal dominant manner, with incomplete penetrance. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. The heme b is bound between the two transmembrane subunits SDHC and SDHD.

Pathway. Carbohydrate metabolism; tricarboxylic acid cycle.

Similarity. Belongs to the cytochrome b560 family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q99643-1	1	yes
Q99643-2	2
Q99643-3	3, CII-3b
Q99643-4	4
Q99643-5	5

RefSeq proteins (12): NP_001030588, NP_001030589, NP_001030590, NP_001265101, NP_001394044, NP_001394045, NP_001394046, NP_001394047, NP_001394048, NP_001394049, NP_001394050, NP_002992* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000701	SuccDH_FuR_B_TM-su	Family
IPR014314	Succ_DH_cytb556	Family
IPR018495	Succ_DH_cyt_bsu_CS	Conserved_site
IPR034804	SQR/QFR_C/D	Homologous_superfamily

Pfam: PF01127

Enzyme classification (BRENDA):

• EC 1.3.5.1 — succinate dehydrogenase (BRENDA: 80 organisms, 226 substrates, 192 inhibitors, 145 Km, 115 kcat entries)

Substrate kinetics (BRENDA)

28 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SUCCINATE	0.0015–20	39
UBIQUINONE	0.0005–0.2	26
FUMARATE	0.005–0.455	14
2,3-DIMETHOXY-5-METHYL-6-DECYL-1,4-BENZOQUINONE	0.0034–0.018	9
REDUCED PLUMBAGIN	0.11–0.19	9
UBIQUINONE-2	0.0002–0.0114	9
MENAQUINOL	0.0009–0.0054	8
PHENAZINE METHOSULFATE	0.11–0.48	3
UBIQUINONE-1	0.0016–0.02	3
2,6-DICHLOROPHENOL INDOPHENOL	0.003–0.007	2
CALDARIELLAQUINONE	0.06–0.18	2
MENAQUINONE	0.0018–0.004	2
OXIDIZED 2,6-DICHLOROPHENOLINDOPHENOL	0.0654–0.089	2
2,3-DIMETHOXY-5-METHYL-1,4-BENZOQUINONE	0.003	1
2,3-DIMETHYL-1,4-NAPHTHOHYDROQUINONE	0.12	1

UniProt features (19 total): helix 5, topological domain 4, splice variant 3, transmembrane region 3, transit peptide 1, chain 1, turn 1, binding site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9KC4	ELECTRON MICROSCOPY	2.65
8GS8	ELECTRON MICROSCOPY	2.86

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99643-F1	91.05	0.77

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 127 (axial binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-611105	Respiratory electron transport
R-HSA-71403	Citric acid cycle (TCA cycle)
R-HSA-9854311	Maturation of TCA enzymes and regulation of TCA cycle
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism

MSigDB gene sets: 520 (showing top): MODULE_93, MORF_RAB5A, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_THE_CH_CH_GROUP_OF_DONORS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, MORF_PSMC2, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GCM_RING1, GOBP_ATP_BIOSYNTHETIC_PROCESS, MORF_ATOX1, GOBP_OXIDATIVE_PHOSPHORYLATION, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS

GO Biological Process (4): tricarboxylic acid cycle (GO:0006099), mitochondrial electron transport, succinate to ubiquinone (GO:0006121), aerobic respiration (GO:0009060), proton motive force-driven mitochondrial ATP synthesis (GO:0042776)

GO Molecular Function (4): electron transfer activity (GO:0009055), heme binding (GO:0020037), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020), respiratory chain complex II (succinate dehydrogenase) (GO:0045273)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	2
Citric acid cycle (TCA cycle)	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
aerobic respiration	1
primary metabolic process	1
aerobic electron transport chain	1
mitochondrial ATP synthesis coupled electron transport	1
cellular respiration	1
mitochondrion	1
oxidative phosphorylation	1
proton motive force-driven ATP synthesis	1
molecular_function	1
tetrapyrrole binding	1
cation binding	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1
membrane protein complex	1
respiratory chain complex	1
oxidoreductase complex	1

Protein interactions and networks

STRING

5189 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SDHC	SDHA	P31040	999
SDHC	SDHAF2	Q9NX18	999
SDHC	SDHD	O14521	999
SDHC	SDHB	P21912	999
SDHC	F5H5T6	F5H5T6	993
SDHC	SDHAF1	A6NFY7	922
SDHC	TMEM127	O75204	903
SDHC	MMUT	P22033	880
SDHC	MT-CYB	P00156	868
SDHC	GAPDH	P00354	838
SDHC	RET	P07949	827
SDHC	PDGFRA	P16234	776
SDHC	ACTB	P02570	765
SDHC	TIMM8B	Q9Y5J9	734
SDHC	KIT	P10721	733

IntAct

39 interactions, top by confidence:

A	B	Type	Score
PRKCA	SDHC	psi-mi:“MI:0915”(physical association)	0.560
YWHAG	SDHC	psi-mi:“MI:0915”(physical association)	0.560
SETDB1	SDHC	psi-mi:“MI:0915”(physical association)	0.560
KAT5	SDHC	psi-mi:“MI:0915”(physical association)	0.560
LMO3	SDHC	psi-mi:“MI:0915”(physical association)	0.560
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
SDHC	DHODH	psi-mi:“MI:0915”(physical association)	0.400
MDM2	SDHC	psi-mi:“MI:0915”(physical association)	0.370
SDHC	ARHGDIA	psi-mi:“MI:0915”(physical association)	0.370
SDHC	XRCC6	psi-mi:“MI:0915”(physical association)	0.370
SDHD	TNNC2	psi-mi:“MI:0914”(association)	0.350
SLC25A5		psi-mi:“MI:0914”(association)	0.350
CLPP	NDUFA4	psi-mi:“MI:2364”(proximity)	0.270
DCTN1	KIF2A	psi-mi:“MI:2364”(proximity)	0.270
FBF1	CCDC85C	psi-mi:“MI:2364”(proximity)	0.270
OFD1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
POC5	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
AKT1	SDHC	psi-mi:“MI:2364”(proximity)	0.270
BRAF	SDHC	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (50): SDHC (Affinity Capture-RNA), SDHC (Co-fractionation), SDHC (Co-fractionation), SDHC (Co-fractionation), SDHC (Co-fractionation), SDHC (Proximity Label-MS), SDHC (Proximity Label-MS), SDHC (Proximity Label-MS), SDHC (Proximity Label-MS), SDHC (Affinity Capture-MS), SDHC (Negative Genetic), SDHC (Positive Genetic), SDHC (Negative Genetic), SDHC (Negative Genetic), SDHC (Negative Genetic)

ESM2 similar proteins: A8WT26, B5FVB8, D0VWV4, O01578, O62215, O74471, O74882, O75964, P04039, P13619, P19511, P33421, P35720, P37298, P38857, P40086, P41955, P41956, P53311, P70097, P92506, P92507, Q04487, Q06236, Q08749, Q10361, Q28852, Q3ZCG2, Q5RFH0, Q6CFW6, Q6CXR8, Q6DGM2, Q6FJJ0, Q6PDU7, Q750S6, Q759E9, Q7SGY6, Q8T2T5, Q8WSR2, Q949R9

Diamond homologs: D0VWV4, O74882, P33421, P35720, P35721, P41085, P41955, P41956, P48934, P48935, P70097, P80478, P80481, P92506, Q1RHB5, Q4UKC1, Q59659, Q68XP1, Q8T2T5, Q92J99, Q99643, Q9CZB0, Q04487, P0DKI0, P0DKI1, Q84VK7, P63725, P63726, P69054, P69055

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SDHC	“form complex”	“Succinate dehydrogenase-Mitochondrial respiratory chain complex II”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Cell Cycle	6	8.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1010 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	69
Likely pathogenic	32
Uncertain significance	455
Likely benign	228
Benign	83

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1040338	NC_000001.10:g.(?161293394)(161293470_?)del	Pathogenic
1069194	NM_003001.5(SDHC):c.250_251del (p.Leu84fs)	Pathogenic
1072500	NM_003001.5(SDHC):c.124del (p.Trp42fs)	Pathogenic
1072825	NC_000001.10:g.(?161310374)(161310455_?)del	Pathogenic
1076621	NC_000001.10:g.(?161332109)(161332308_?)del	Pathogenic
1076622	NC_000001.10:g.(?161326457)(161332308_?)del	Pathogenic
1443862	NC_000001.10:g.(?161310374)(161332308_?)del	Pathogenic
1456907	NM_003001.5(SDHC):c.214del (p.Arg72fs)	Pathogenic
1744549	NM_003001.5(SDHC):c.118del (p.Arg40fs)	Pathogenic
1767917	NM_003001.5(SDHC):c.97_98dup (p.Ala34fs)	Pathogenic
183753	NM_003001.5(SDHC):c.397C>T (p.Arg133Ter)	Pathogenic
189840	NM_003001.5(SDHC):c.6del (p.Ala3fs)	Pathogenic
1999178	NM_003001.5(SDHC):c.21-1G>A	Pathogenic
2036254	NM_003001.5(SDHC):c.220dup (p.Thr74fs)	Pathogenic
2036721	NM_003001.5(SDHC):c.288dup (p.Glu97Ter)	Pathogenic
2055039	NM_003001.5(SDHC):c.1A>C (p.Met1Leu)	Pathogenic
229958	NM_003001.5(SDHC):c.376dup (p.Tyr126fs)	Pathogenic
239456	NM_003001.3(SDHC):c.406-?_*2318+?del	Pathogenic
2424599	NC_000001.10:g.(?161298176)(161298297_?)del	Pathogenic
2424601	NC_000001.10:g.(?161284158)(161284225_?)del	Pathogenic
2442323	NM_003001.5(SDHC):c.49del (p.His17fs)	Pathogenic
2573281	NM_003001.5(SDHC):c.107_108del (p.Glu36fs)	Pathogenic
2573308	NM_003001.5(SDHC):c.177C>A (p.Tyr59Ter)	Pathogenic
2637552	NM_003001.5(SDHC):c.248_251del (p.Ser83fs)	Pathogenic
2943040	NM_003001.5(SDHC):c.2T>C (p.Met1Thr)	Pathogenic
2950878	NM_003001.5(SDHC):c.61C>T (p.Gln21Ter)	Pathogenic
2954043	NM_003001.5(SDHC):c.143_144insTGGCCGGGCGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGCGGATCACGANNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAGAATATAGGTTC (p.Ser48_Asn49insGlyArgAlaArgTrpLeuThrProValIleProAlaLeuTrpGluAlaGluAlaGlyGlySerArgXaaXaaXaaXaaLysLysLysLysLysLysLysAsnIleGlySer)	Pathogenic
3148693	NM_003001.5(SDHC):c.204dup (p.Ile69fs)	Pathogenic
3223027	NM_003001.5(SDHC):c.183G>A (p.Trp61Ter)	Pathogenic
3247756	NC_000001.10:g.(?161284196)(161284215_?)del	Pathogenic

SpliceAI

1065 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161323667:GAAA:G	donor_gain	1.0000
1:161328394:A:AG	acceptor_gain	1.0000
1:161328395:G:GG	acceptor_gain	1.0000
1:161328395:GTGCT:G	acceptor_gain	1.0000
1:161340588:TTACA:T	acceptor_loss	1.0000
1:161340589:TACA:T	acceptor_loss	1.0000
1:161340590:ACAG:A	acceptor_loss	1.0000
1:161340591:CA:C	acceptor_loss	1.0000
1:161340592:A:AC	acceptor_loss	1.0000
1:161340592:A:AG	acceptor_gain	1.0000
1:161340592:AGTT:A	acceptor_gain	1.0000
1:161340592:AGTTG:A	acceptor_gain	1.0000
1:161340593:G:GC	acceptor_gain	1.0000
1:161340593:GTT:G	acceptor_gain	1.0000
1:161340593:GTTG:G	acceptor_gain	1.0000
1:161340593:GTTGG:G	acceptor_gain	1.0000
1:161356675:AGG:A	acceptor_gain	1.0000
1:161356676:GGG:G	acceptor_gain	1.0000
1:161362440:G:GT	donor_gain	1.0000
1:161314444:G:GT	donor_gain	0.9900
1:161323612:A:AG	acceptor_gain	0.9900
1:161323613:G:GG	acceptor_gain	0.9900
1:161323613:GACAC:G	acceptor_gain	0.9900
1:161323671:G:GG	donor_gain	0.9900
1:161340593:GT:G	acceptor_gain	0.9900
1:161340653:CAGG:C	donor_loss	0.9900
1:161340654:AGGT:A	donor_loss	0.9900
1:161340656:G:A	donor_loss	0.9900
1:161340657:T:G	donor_loss	0.9900
1:161356782:C:G	donor_gain	0.9900

AlphaMissense

1087 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161356835:C:G	H134D	0.992
1:161340649:A:C	S79R	0.990
1:161340651:T:A	S79R	0.990
1:161340651:T:G	S79R	0.990
1:161362332:T:A	W137R	0.990
1:161362332:T:C	W137R	0.990
1:161328439:T:C	F41L	0.989
1:161328441:C:A	F41L	0.989
1:161328441:C:G	F41L	0.989
1:161362336:A:C	D138A	0.989
1:161340629:G:C	R72P	0.988
1:161356814:C:G	H127D	0.988
1:161362334:G:C	W137C	0.988
1:161362334:G:T	W137C	0.988
1:161356811:T:G	Y126D	0.986
1:161356825:T:A	N130K	0.985
1:161356825:T:G	N130K	0.985
1:161356826:G:T	G131W	0.985
1:161356833:G:C	R133P	0.985
1:161340628:C:A	R72S	0.984
1:161362336:A:T	D138V	0.984
1:161356803:C:G	P123R	0.983
1:161340625:C:G	H71D	0.981
1:161362335:G:C	D138H	0.981
1:161356692:G:A	G86D	0.980
1:161356826:G:A	G131R	0.980
1:161356826:G:C	G131R	0.980
1:161356816:T:A	H127Q	0.979
1:161356816:T:G	H127Q	0.979
1:161356820:T:A	W129R	0.979

dbSNP variants (sampled 300 via entrez): RS1000003724 (1:161331644 G>A), RS1000054039 (1:161375202 G>C), RS1000138851 (1:161359469 C>T), RS1000157895 (1:161349980 G>A), RS1000178927 (1:161356301 G>A), RS1000228570 (1:161351471 A>G), RS1000238232 (1:161314686 C>G,T), RS1000252441 (1:161355962 G>A,T), RS1000284347 (1:161326239 G>A), RS1000398132 (1:161369334 C>T), RS1000466627 (1:161321135 T>A), RS1000560965 (1:161337761 G>A), RS1000561761 (1:161319975 A>G), RS1000596617 (1:161355594 G>A), RS1000646888 (1:161342644 G>A)

Disease associations

OMIM: gene MIM:602413 | disease phenotypes: MIM:605373, MIM:606764, MIM:168000, MIM:606864, MIM:171300, MIM:158350, MIM:167000, MIM:604287

GenCC curated gene-disease

Disease	Classification	Inheritance
pheochromocytoma/paraganglioma syndrome 3	Definitive	Autosomal dominant
hereditary pheochromocytoma-paraganglioma	Definitive	Autosomal dominant
gastrointestinal stromal tumor	Strong	Autosomal dominant
Carney-Stratakis syndrome	Strong	Autosomal dominant
renal cell carcinoma	Moderate	Autosomal dominant
Cowden disease	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
hereditary pheochromocytoma-paraganglioma	Definitive	AD
mitochondrial disease	No Known Disease Relationship	UD

Mondo (13): pheochromocytoma/paraganglioma syndrome 3 (MONDO:0011544), gastrointestinal stromal tumor (MONDO:0011719), hereditary neoplastic syndrome (MONDO:0015356), hereditary pheochromocytoma-paraganglioma (MONDO:0017366), Carney-Stratakis syndrome (MONDO:0011740), pheochromocytoma (MONDO:0008233), Cowden disease (MONDO:0016063), breast cancer (MONDO:0007254), ovarian cancer (MONDO:0008170), Carney triad (MONDO:0011424), neuroblastoma (MONDO:0005072), rhabdomyosarcoma (MONDO:0005212), renal cell carcinoma (MONDO:0005086)

Orphanet (9): Inherited cancer-predisposing syndrome (Orphanet:140162), Hereditary pheochromocytoma-paraganglioma (Orphanet:29072), Gastrointestinal stromal tumor (Orphanet:44890), Carney-Stratakis syndrome (Orphanet:97286), Cowden syndrome (Orphanet:201), Rare ovarian cancer (Orphanet:213500), Carney triad (Orphanet:139411), Neuroblastoma (Orphanet:635), Rhabdomyosarcoma (Orphanet:780)

HPO phenotypes

144 total (30 of 144 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000036	Abnormal penis morphology
HP:0000077	Abnormality of the kidney
HP:0000093	Proteinuria
HP:0000096	Glomerular sclerosis
HP:0000130	Abnormality of the uterus
HP:0000158	Macroglossia
HP:0000218	High palate
HP:0000221	Furrowed tongue
HP:0000256	Macrocephaly
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000405	Conductive hearing impairment
HP:0000518	Cataract
HP:0000526	Aniridia
HP:0000545	Myopia
HP:0000717	Autism
HP:0000740	Episodic paroxysmal anxiety
HP:0000767	Pectus excavatum
HP:0000771	Gynecomastia
HP:0000790	Hematuria
HP:0000820	Abnormality of the thyroid gland
HP:0000822	Hypertension
HP:0000853	Goiter
HP:0000953	Hyperpigmentation of the skin
HP:0000975	Hyperhidrosis
HP:0000980	Pallor
HP:0000982	Palmoplantar keratoderma
HP:0000988	Skin rash
HP:0000995	Melanocytic nevus

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001523_16	Visceral adipose tissue adjusted for BMI	8.000000e-06
GCST005352_1	Paclitaxel disposition in epithelial ovarian cancer	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

MeSH disease descriptors (11)

Descriptor	Name	Tree numbers
D002292	Carcinoma, Renal Cell	C04.557.470.200.025.390; C04.588.945.947.535.160; C12.050.351.937.820.535.160; C12.050.351.968.419.473.160; C12.200.758.820.750.160; C12.200.777.419.473.160; C12.900.820.535.160; C12.950.419.473.160; C12.950.983.535.160
D046152	Gastrointestinal Stromal Tumors	C04.557.450.565.370; C06.301.371.308; C06.405.249.308
D006223	Hamartoma Syndrome, Multiple	C04.445.435; C04.651.435; C04.700.435; C16.320.700.435
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D009447	Neuroblastoma	C04.557.465.625.600.590.650.550; C04.557.470.670.590.650.550; C04.557.580.625.600.590.650.550
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705
D010673	Pheochromocytoma	C04.557.465.625.650.700.725; C04.557.580.625.650.700.725
D012208	Rhabdomyosarcoma	C04.557.450.590.550.660; C04.557.450.795.550.660
C565803	Carney Triad (supp.)
C564650	Carney-Stratakis Syndrome (supp.)
C565335	Paragangliomas 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Quercetin	decreases expression	3
bisphenol A	affects expression, increases expression, decreases reaction, increases abundance	2
Acetaminophen	decreases expression	2
Atrazine	decreases expression	2
Cisplatin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	increases expression	1
TAK-243	decreases sumoylation	1
ginger extract	decreases reaction, increases abundance, increases expression	1
lasiocarpine	decreases expression	1
triphenyl phosphate	affects expression	1
4-chlorobiphenyl	decreases expression	1
chlortoluron	decreases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases abundance, affects cotreatment, decreases expression	1
cobaltous chloride	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
JP8 aviation fuel	affects expression	1
corosolic acid	decreases expression	1
K 7174	decreases expression	1
pluronic block copolymer p85	decreases expression	1
Bortezomib	decreases expression	1
Arsenic Trioxide	increases expression	1
Arsenic	decreases expression, increases abundance, affects cotreatment	1
Benzo(a)pyrene	affects methylation	1
Cannabidiol	increases expression	1
Curcumin	affects binding	1
Doxorubicin	affects expression	1

Clinical trials (associated diseases)

597 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00414765	PHASE4	COMPLETED	Aldesleukin in Participants With Metastatic Renal Cell Carcinoma or Metastatic Melanoma
NCT00777504	PHASE4	UNKNOWN	Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors
NCT00930345	PHASE4	TERMINATED	Biological, Pathological and Imagery Markers in the First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma
NCT01206764	PHASE4	COMPLETED	A Trial of Everolimis in Patients With Advanced Renal Cell Carcinoma.
NCT01266837	PHASE4	COMPLETED	Open Label, Single Arm Trial to Characterize Patients With Metastatic RCC Treated With Everolimus After Failure of the First VEGF-targeted Therapy (MARC-2)
NCT02056587	PHASE4	COMPLETED	Everolimus in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
NCT02338570	PHASE4	TERMINATED	Outcome-related Factors in Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus (ORCHIDEE)
NCT02596035	PHASE4	COMPLETED	An Investigational Immuno-therapy Safety Trial of Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma
NCT02982954	PHASE4	COMPLETED	A Study to Evaluate the Safety of Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Cancer
NCT05949424	PHASE4	UNKNOWN	OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
NCT07028125	PHASE4	RECRUITING	Digital Monitoring of Self-reported Symptoms by Patients Treated With Cabozantinib Plus Nivolumab for Advanced Clear-cell Renal Carcinoma
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT00171977	PHASE4	COMPLETED	Post-Marketing Clinical Study of Postoperative Adjuvant Therapy With Imatinib Mesylate in Patients With Gastrointestinal Stromal Tumors (GIST)
NCT00510354	PHASE4	COMPLETED	Treatment of Patients With Everolimus and Imatinib Mesylate Who Have Progressive Gastro Intestinal Stromal Tumors (GIST) and Are Resistant to Imatinib Mesylate
NCT00756509	PHASE4	COMPLETED	Treatment of Patients With Metastatic or Unresectable Gastrointestinal Stromal Tumors in First Line With Nilotinib
NCT02800330	PHASE4	COMPLETED	The Effects of the Proton Pump Inhibitor Esomeprazole on the Bioavailability of Regorafenib
NCT04825574	PHASE4	COMPLETED	Study for Patients Previously Treated in Avapritinib Clinical Trials
NCT00033904	PHASE3	COMPLETED	Survival Study Of Oncophage® vs. Observation In Patients With Kidney Cancer
NCT00126178	PHASE3	TERMINATED	Clinical Trial Studying a Personalized Cancer Vaccine in Patients With Non-metastatic Kidney Cancer
NCT00291369	PHASE3	COMPLETED	Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis
NCT00410124	PHASE3	COMPLETED	RAD001 Plus Best Supportive Care (BSC) Versus BSC Plus Placebo in Patients With Metastatic Carcinoma of the Kidney Which Has Progressed After Treatment With Sorafenib and/or Sunitinib
NCT00474786	PHASE3	COMPLETED	Temsirolimus Versus Sorafenib As Second-Line Therapy In Patients With Advanced RCC Who Have Failed First-Line Sunitinib
NCT00478114	PHASE3	COMPLETED	Efficacy and Safety of Sorafenib in Advanced Renal Cell Carcinoma (RCC)
NCT00606632	PHASE3	COMPLETED	Pre-surgical Detection of Clear Cell Renal Cell Carcinoma (ccRCC) Using Radiolabeled G250-Antibody
NCT00606866	PHASE3	COMPLETED	MRI Study of BAY 43-9006 in Metastatic Renal Cell Carcinoma
NCT00631371	PHASE3	COMPLETED	Study Comparing Bevacizumab + Temsirolimus vs. Bevacizumab + Interferon-Alfa In Advanced Renal Cell Carcinoma Subjects
NCT00732914	PHASE3	COMPLETED	Sequential Study to Treat Renal Cell Carcinoma
NCT00869011	PHASE3	UNKNOWN	Exercise for Patients With Renal Cell Cancer Receiving Sunitinib
NCT00930033	PHASE3	COMPLETED	Clinical Trial to Assess the Importance of Nephrectomy
NCT01030783	PHASE3	COMPLETED	A Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma
NCT01076010	PHASE3	COMPLETED	An Extension Treatment Protocol for Subjects Who Have Participated in a Study of Tivozanib Versus Sorafenib in Kidney Carcinoma (Protocol AV-951-09-301).
NCT01198158	PHASE3	TERMINATED	Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy
NCT01223027	PHASE3	COMPLETED	Study of Dovitinib Versus Sorafenib in Patients With Metastatic Renal Cell Carcinoma
NCT01224288	PHASE3	ACTIVE_NOT_RECRUITING	Dynamic Contrast Enhancement Computed Tomography for Evaluating Tumor Perfusion in Patients With Metastatic Renal Cell Carcinoma Receiving Targeted Therapies: Renal Cell Carcinoma (RCC) Scramble
NCT01235962	PHASE3	COMPLETED	A Study to Evaluate Pazopanib as an Adjuvant Treatment for Localized Renal Cell Carcinoma (RCC)
NCT01265810	PHASE3	COMPLETED	Caphosol in Oral Mucositis Due to Targeted Therapy
NCT01265901	PHASE3	COMPLETED	IMA901 in Patients Receiving Sunitinib for Advanced/Metastatic Renal Cell Carcinoma
NCT01481870	PHASE3	UNKNOWN	Comparison of Sequential Therapies With Sunitinib and Sorafenib in Advanced Renal Cell Carcinoma
NCT01582672	PHASE3	TERMINATED	Phase 3 Trial of Autologous Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma
NCT01613846	PHASE3	COMPLETED	Phase III Sequential Open-label Study to Evaluate the Efficacy and Safety of Sorafenib Followed by Pazopanib Versus Pazopanib Followed by Sorafenib in the Treatment of Advanced / Metastatic Renal Cell Carcinoma (SWITCH-II)