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GeneBe

SDHC

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

Basic information

Region (hg38): 1:161314380-161363206

Previous symbols: [ "PGL3" ]

Links

ENSG00000143252NCBI:6391OMIM:602413HGNC:10682Uniprot:Q99643AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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
  • paragangliomas 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
  • paragangliomas 3 (Definitive), mode of inheritance: AD
  • gastrointestinal stromal tumor (Strong), mode of inheritance: AD
  • paragangliomas 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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Paraganglioma and gastric stromal sarcoma; Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 3ADOncologicThe condition involves increased risk of certain types of neoplasms, and surveillance/early treatment of tumors (eg, surgical resection) may be beneficialOncologic15342702; 15342702; 16249420; 17804857; 17667967; 21173220; 21348866; 22703879

ClinVar

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

  • Gastrointestinal stromal tumor;Paragangliomas 3 (302 variants)
  • Hereditary cancer-predisposing syndrome (296 variants)
  • Paragangliomas 3;Gastrointestinal stromal tumor (171 variants)
  • not provided (127 variants)
  • not specified (58 variants)
  • Hereditary pheochromocytoma-paraganglioma (36 variants)
  • Gastrointestinal stromal tumor (36 variants)
  • Paragangliomas 3 (34 variants)
  • SDHC-related condition (9 variants)
  • Pheochromocytoma (8 variants)
  • Carney triad (3 variants)
  • Carney-Stratakis syndrome (2 variants)
  • Carney-Stratakis syndrome;Paragangliomas 3;Gastrointestinal stromal tumor (1 variants)
  • Rhabdomyosarcoma (1 variants)
  • Neuroblastoma (1 variants)
  • Gastrointestinal stromal tumor;Carney-Stratakis syndrome;Paragangliomas 3 (1 variants)
  • Ovarian cancer (1 variants)
  • Gastrointestinal stromal tumor;Paragangliomas 3;Carney-Stratakis syndrome (1 variants)
  • Malignant tumor of breast (1 variants)
  • Paragangliomas 3;Carney-Stratakis syndrome;Gastrointestinal stromal tumor (1 variants)
  • Charcot-Marie-Tooth, Intermediate (1 variants)
  • Roussy-Lévy syndrome (1 variants)
  • Carney-Stratakis syndrome;Gastrointestinal stromal tumor;Paragangliomas 3 (1 variants)
  • Paragangliomas 3;Gastrointestinal stromal tumor;Carney-Stratakis syndrome (1 variants)
  • Charcot-Marie-Tooth disease type 4E (1 variants)
  • Charcot-Marie-Tooth disease, type I (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.

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.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
1
clinvar
79
clinvar
80
missense
3
clinvar
6
clinvar
265
clinvar
25
clinvar
299
nonsense
6
clinvar
3
clinvar
2
clinvar
11
start loss
4
clinvar
1
clinvar
5
frameshift
21
clinvar
3
clinvar
24
inframe indel
2
clinvar
2
splice donor/acceptor (+/-2bp)
3
clinvar
18
clinvar
1
clinvar
22
splice region
26
19
45
non coding
22
clinvar
78
clinvar
50
clinvar
150
Total 37 28 296 182 50

Highest pathogenic variant AF is 0.0000197

Variants in SDHC

This is a list of pathogenic ClinVar variants found in the SDHC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
1-161314392-G-C not specified Likely benign (Aug 15, 2023)2575490
1-161314392-G-T Hereditary pheochromocytoma-paraganglioma Uncertain significance (Aug 08, 2023)3072560
1-161314394-C-G Hereditary pheochromocytoma-paraganglioma Uncertain significance (May 16, 2023)3070766
1-161314401-C-A Hereditary cancer-predisposing syndrome Uncertain significance (Aug 19, 2022)1750980
1-161314401-C-T Hereditary cancer-predisposing syndrome Uncertain significance (Feb 01, 2022)1750990
1-161314402-C-G Hereditary pheochromocytoma-paraganglioma Uncertain significance (Apr 03, 2023)3070129
1-161314402-C-T Hereditary cancer-predisposing syndrome Uncertain significance (Aug 11, 2017)486435
1-161314403-A-G Hereditary cancer-predisposing syndrome Uncertain significance (Mar 12, 2024)232369
1-161314405-G-A Hereditary cancer-predisposing syndrome Uncertain significance (Oct 04, 2023)1784205
1-161314406-A-C Gastrointestinal stromal tumor;Paragangliomas 3 Pathogenic (Dec 23, 2021)2055039
1-161314406-A-G Paragangliomas 3 • Hereditary cancer-predisposing syndrome • Paragangliomas 3;Gastrointestinal stromal tumor Pathogenic (Feb 15, 2024)407060
1-161314406-A-T Paragangliomas 3;Gastrointestinal stromal tumor • Paragangliomas 3 Pathogenic (Dec 26, 2023)653751
1-161314407-T-C Paragangliomas 3;Gastrointestinal stromal tumor Pathogenic (Jan 09, 2023)2943040
1-161314407-T-G Gastrointestinal stromal tumor;Paragangliomas 3 Likely pathogenic (Oct 06, 2019)968839
1-161314408-G-A Paragangliomas 3 • Gastrointestinal stromal tumor;Paragangliomas 3 Pathogenic (Feb 15, 2024)7241
1-161314409-G-A Gastrointestinal stromal tumor;Paragangliomas 3 • Hereditary cancer-predisposing syndrome • Gastrointestinal stromal tumor Uncertain significance (Aug 17, 2023)465977
1-161314409-G-C Gastrointestinal stromal tumor;Paragangliomas 3 Uncertain significance (Apr 22, 2023)852372
1-161314410-C-G Paragangliomas 3;Gastrointestinal stromal tumor • Hereditary cancer-predisposing syndrome Uncertain significance (Dec 07, 2023)663942
1-161314410-C-T Paragangliomas 3;Gastrointestinal stromal tumor • Hereditary cancer-predisposing syndrome Uncertain significance (Nov 02, 2023)2625945
1-161314410-CT-C Carney triad • Hereditary cancer-predisposing syndrome Pathogenic (May 08, 2013)189840
1-161314411-T-A Paragangliomas 3;Gastrointestinal stromal tumor • Hereditary pheochromocytoma-paraganglioma Likely benign (Apr 14, 2023)2946701
1-161314411-T-C Gastrointestinal stromal tumor;Paragangliomas 3 • Hereditary cancer-predisposing syndrome • Hereditary pheochromocytoma-paraganglioma Likely benign (Dec 18, 2023)220994
1-161314411-T-G Gastrointestinal stromal tumor;Paragangliomas 3 • Hereditary cancer-predisposing syndrome Likely benign (Jul 15, 2023)1570436
1-161314412-G-A Paragangliomas 3;Gastrointestinal stromal tumor • Hereditary cancer-predisposing syndrome • Hereditary pheochromocytoma-paraganglioma • Gastrointestinal stromal tumor Uncertain significance (Feb 01, 2024)407063
1-161314412-G-C Paragangliomas 3;Gastrointestinal stromal tumor Uncertain significance (Apr 20, 2023)2946953

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SDHCprotein_codingprotein_codingENST00000367975 648938
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.0002010.7401256750211256960.0000835
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.8257496.80.7640.000005331081
Missense in Polyphen1829.0020.62064334
Synonymous-0.1653735.71.040.00000191355
Loss of Function0.990710.50.6696.19e-7107

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00002920.0000292
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.00004620.0000462
European (Non-Finnish)0.0001260.000123
Middle Eastern0.00005440.0000544
South Asian0.0001310.000131
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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