SDHC

succinate dehydrogenase complex subunit C, the group of Mitochondrial complex II: succinate dehydrogenase subunits

Basic information

Region (hg38): 1:161314381-161363206

Previous symbols: [ "PGL3" ]

Links

ENSG00000143252 ∙ NCBI:6391 ∙ OMIM:602413 ∙ HGNC:10682 ∙ Uniprot:Q99643 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Carney-Stratakis syndrome (Strong), mode of inheritance: AD
• gastrointestinal stromal tumor (Strong), mode of inheritance: AD
• renal cell carcinoma (Moderate), mode of inheritance: AD
• pheochromocytoma/paraganglioma syndrome 3 (Strong), mode of inheritance: AD
• Cowden disease (Supportive), mode of inheritance: AD
• hereditary pheochromocytoma-paraganglioma (Supportive), mode of inheritance: AD
• Carney-Stratakis syndrome (Supportive), mode of inheritance: AD
• pheochromocytoma/paraganglioma syndrome 3 (Definitive), mode of inheritance: AD
• gastrointestinal stromal tumor (Strong), mode of inheritance: AD
• pheochromocytoma/paraganglioma syndrome 3 (Strong), mode of inheritance: AD
• hereditary pheochromocytoma-paraganglioma (Definitive), mode of inheritance: AD
• mitochondrial disease (No Known Disease Relationship), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Paraganglioma and gastric stromal sarcoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3	AD	Oncologic	The condition involves increased risk of certain types of neoplasms, and surveillance/early treatment of tumors (eg, surgical resection) may be beneficial	Oncologic	15342702; 15342702; 16249420; 17804857; 17667967; 21173220; 21348866; 22703879

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SDHC gene.

• Pheochromocytoma/paraganglioma_syndrome_3 (662 variants)
• Gastrointestinal_stromal_tumor (616 variants)
• Hereditary_cancer-predisposing_syndrome (408 variants)
• not_provided (119 variants)
• Hereditary_pheochromocytoma-paraganglioma (114 variants)
• not_specified (58 variants)
• Carney-Stratakis_syndrome (19 variants)
• SDHC-related_disorder (18 variants)
• Carney_triad (3 variants)
• Pheochromocytoma (3 variants)
• Inherited_phaeochromocytoma_and_paraganglioma_excluding_NF1 (3 variants)
• Cowden_syndrome (2 variants)
• Rhabdomyosarcoma (1 variants)
• Neuroblastoma (1 variants)
• Ovarian_cancer (1 variants)
• Malignant_tumor_of_breast (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SDHC gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003001.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	150	12	165
missense	2	19	338	5	1	365
nonsense	8	4	1			13
start loss	6	1				7
frameshift	28	5	6	1		40
splice donor/acceptor (+/-2bp)	3	25	1			29
Total	47	54	349	156	13

Highest pathogenic variant AF is 0.000048328693

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SDHC	protein_coding	protein_coding	ENST00000367975	6	48938

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000201	0.740	125675	0	21	125696	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.825	74	96.8	0.764	0.00000533	1081
Missense in Polyphen		18	29.002	0.62064		334
Synonymous	-0.165	37	35.7	1.04	0.00000191	355
Loss of Function	0.990	7	10.5	0.669	6.19e-7	107

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000292	0.0000292
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000126	0.000123
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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).
• Disease: DISEASE: Paragangliomas 3 (PGL3) [MIM:605373]: A neural crest tumor usually derived from the chromoreceptor tissue of a paraganglion. Paragangliomas can develop at various body sites, including the head, neck, thorax and abdomen. Most commonly, they are located in the head and neck region, specifically at the carotid bifurcation, the jugular foramen, the vagal nerve, and in the middle ear. {ECO:0000269|PubMed:11062460}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:17804857}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Citrate cycle (TCA cycle) - Homo sapiens (human);Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Huntington,s disease - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Parkinson,s disease - Homo sapiens (human);Warburg Effect;Mitochondrial Electron Transport Chain;The oncogenic action of Succinate;The oncogenic action of Fumarate;Pyruvate dehydrogenase deficiency (E3);Pyruvate dehydrogenase deficiency (E2);2-ketoglutarate dehydrogenase complex deficiency;Mitochondrial complex II deficiency;Fumarase deficiency;Congenital lactic acidosis;Citric Acid Cycle;Glutaminolysis and Cancer;The oncogenic action of 2-hydroxyglutarate;The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria;The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria ;Electron Transport Chain;TCA Cycle;Citrate cycle;Citric acid cycle (TCA cycle);Pyruvate metabolism and Citric Acid (TCA) cycle;Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;TCA cycle;TCA cycle;Arginine Proline metabolism;superpathway of conversion of glucose to acetyl CoA and entry into the TCA cycle;Tyrosine metabolism;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.354

Intolerance Scores

• loftool: 0.335
• rvis_EVS: 0.39
• rvis_percentile_EVS: 75.87

Haploinsufficiency Scores

• pHI: 0.216
• hipred: Y
• hipred_score: 0.553
• ghis: 0.413

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.994

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sdhc
• Phenotype: homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; skeleton phenotype

Gene ontology

• Biological process: tricarboxylic acid cycle;mitochondrial electron transport, succinate to ubiquinone;aerobic respiration;oxidation-reduction process
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone);integral component of membrane;respiratory chain complex II
• Molecular function: succinate dehydrogenase (ubiquinone) activity;electron transfer activity;heme binding;metal ion binding