SDHD
succinate dehydrogenase complex subunit D, the group of Mitochondrial complex II: succinate dehydrogenase subunits
Basic information
Region (hg38): 11:112086824-112120016
Previous symbols: [ "PGL", "PGL1" ]
Links
Phenotypes
GenCC
Source:
- Carney-Stratakis syndrome (Strong), mode of inheritance: AD
- renal cell carcinoma (Moderate), mode of inheritance: AD
- Cowden disease (Supportive), mode of inheritance: AD
- mitochondrial complex II deficiency (Supportive), mode of inheritance: AR
- hereditary pheochromocytoma-paraganglioma (Supportive), mode of inheritance: AD
- Carney-Stratakis syndrome (Supportive), mode of inheritance: AD
- pheochromocytoma/paraganglioma syndrome 1 (Definitive), mode of inheritance: AD
- mitochondrial complex II deficiency (Moderate), mode of inheritance: AR
- mitochondrial complex II deficiency, nuclear type 1 (Strong), mode of inheritance: AR
- Carney-Stratakis syndrome (Strong), mode of inheritance: AD
- pheochromocytoma/paraganglioma syndrome 1 (Strong), mode of inheritance: AD
- mitochondrial disease (Limited), mode of inheritance: AR
- hereditary pheochromocytoma-paraganglioma (Definitive), mode of inheritance: AD
- pheochromocytoma/paraganglioma syndrome 1 (Definitive), mode of inheritance: AD
- intestinal cancer (Limited), mode of inheritance: AD
- pheochromocytoma (Definitive), mode of inheritance: AD
- mitochondrial complex 2 deficiency, nuclear type 3 (Moderate), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Cowden syndrome 3; Paraganglioma and gastric stromal sarcoma; Pheochromocytoma/paraganglioma syndrome 1; Carcinoid tumors, intestinal; Mitochondrial complex II deficiency, nuclear type 3 | AD/AR | Biochemical; Cardiovascular; Oncologic | In conditions related to neoplasms, surveillance for and early diagnosis/treatment of associated neoplasms can be beneficial; In Mitochondrial respiratory chain complex II deficiency, medical treatment (eg, with riboflavin, ubiquinol) may be beneficial, and individuals may have cardiac involvement such that surveillance may be beneficial | Biochemical; Cardiovascular; Neurologic; Oncologic | 10657297; 11156372; 11526495; 11343322; 11519521; 12000816; 12205103; 12111639; 12007193; 12811540; 15032977; 15479192; 15328326; 16317055; 17848412; 17804857; 17667967; 18678321; 19239085; 19584903; 21348866; 21565294; 22261759; 22948026; 23072324; 23099648; 23322652; 24367056; 26008905 |
ClinVar
This is a list of variants' phenotypes submitted to
- Pheochromocytoma (619 variants)
- Carney-Stratakis_syndrome (615 variants)
- Cowden_syndrome_3 (613 variants)
- Paragangliomas_with_sensorineural_hearing_loss (611 variants)
- Hereditary_cancer-predisposing_syndrome (428 variants)
- Pheochromocytoma/paraganglioma_syndrome_1 (172 variants)
- Hereditary_pheochromocytoma-paraganglioma (132 variants)
- not_provided (129 variants)
- Mitochondrial_complex_2_deficiency,_nuclear_type_3 (58 variants)
- not_specified (30 variants)
- SDHD-related_disorder (20 variants)
- Mitochondrial_complex_II_deficiency,_nuclear_type_1 (4 variants)
- Paraganglioma (2 variants)
- Pheochromocytoma/paraganglioma_syndrome_3 (1 variants)
- Pheochromocytoma/paraganglioma_syndrome_4 (1 variants)
- Fatal_infantile_mitochondrial_cardiomyopathy (1 variants)
- Microcephaly (1 variants)
- EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
- Carcinoid_tumor_of_intestine (1 variants)
- Cowden_syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the SDHD gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003002.4. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 141 | 10 | 155 | |||
| missense | 25 | 343 | 15 | 393 | ||
| nonsense | 25 | 31 | ||||
| start loss | 5 | 1 | 6 | |||
| frameshift | 40 | 18 | 60 | |||
| splice donor/acceptor (+/-2bp) | 10 | 12 | 23 | |||
| Total | 89 | 59 | 353 | 156 | 11 |
Highest pathogenic variant AF is 0.000034465753
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| SDHD | protein_coding | protein_coding | ENST00000375549 | 4 | 32857 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.337 | 0.650 | 125744 | 0 | 3 | 125747 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.166 | 90 | 85.7 | 1.05 | 0.00000429 | 1003 |
| Missense in Polyphen | 18 | 22.856 | 0.78754 | 299 | ||
| Synonymous | 0.749 | 28 | 33.5 | 0.836 | 0.00000182 | 345 |
| Loss of Function | 2.09 | 2 | 8.61 | 0.232 | 5.26e-7 | 83 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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). {ECO:0000250}.;
- Disease
- DISEASE: Paragangliomas 1 (PGL1) [MIM:168000]: A neural crest tumor usually derived from the chromoreceptor tissue of a paraganglion. PGL1 is a rare autosomal dominant disorder which is characterized by the development of mostly benign, highly vascular, slowly growing tumors in the head and neck. In the head and neck region, the carotid body is the largest of all paraganglia and is also the most common site of the tumors. {ECO:0000269|PubMed:10657297, ECO:0000269|PubMed:11343322, ECO:0000269|PubMed:11391796, ECO:0000269|PubMed:11391798, ECO:0000269|PubMed:15328326}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pheochromocytoma (PCC) [MIM:171300]: A catecholamine- producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. {ECO:0000269|PubMed:11156372, ECO:0000269|PubMed:12000816, ECO:0000269|PubMed:15328326}. Note=Disease susceptibility is associated with variations 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.; DISEASE: Mitochondrial complex II deficiency (MT-C2D) [MIM:252011]: A disorder of the mitochondrial respiratory chain with heterogeneous clinical manifestations. Clinical features include psychomotor regression in infants, poor growth with lack of speech development, severe spastic quadriplegia, dystonia, progressive leukoencephalopathy, muscle weakness, exercise intolerance, cardiomyopathy. Some patients manifest Leigh syndrome or Kearns-Sayre syndrome. {ECO:0000269|PubMed:24367056, ECO:0000269|PubMed:26008905}. 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
- 0.617
Intolerance Scores
- loftool
- 0.131
- rvis_EVS
- 0.46
- rvis_percentile_EVS
- 78.16
Haploinsufficiency Scores
- pHI
- 0.205
- hipred
- Y
- hipred_score
- 0.598
- ghis
- 0.529
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.746
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Sdhd
- Phenotype
- endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); 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); normal phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype;
Gene ontology
- Biological process
- tricarboxylic acid cycle;mitochondrial electron transport, succinate to ubiquinone
- Cellular component
- mitochondrion;mitochondrial envelope;mitochondrial inner membrane;mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone);integral component of membrane
- Molecular function
- succinate dehydrogenase activity;succinate dehydrogenase (ubiquinone) activity;electron transfer activity;heme binding;metal ion binding;ubiquinone binding