SDHB

succinate dehydrogenase complex iron sulfur subunit B, the group of Mitochondrial complex II: succinate dehydrogenase subunits

Basic information

Region (hg38): 1:17018721-17054032

Previous symbols: [ "SDH1", "SDH" ]

Links

ENSG00000117118 ∙ NCBI:6390 ∙ OMIM:185470 ∙ HGNC:10681 ∙ Uniprot:P21912 ∙ 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 (Strong), mode of inheritance: AD
• paragangliomas 4 (Strong), mode of inheritance: AD
• paragangliomas 4 (Definitive), 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
• mitochondrial complex 2 deficiency, nuclear type 4 (Strong), mode of inheritance: AR
• gastrointestinal stromal tumor (Definitive), mode of inheritance: AD
• Carney-Stratakis syndrome (Definitive), mode of inheritance: Mitochondrial
• gastrointestinal stromal tumor (Strong), mode of inheritance: AD
• paragangliomas 4 (Strong), mode of inheritance: AD
• mitochondrial disease (Definitive), mode of inheritance: AR
• hereditary pheochromocytoma-paraganglioma (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cowden syndrome 2; Paraganglioma and gastric stromal sarcoma; Gastrointestinal stromal tumor; Pheochromocytoma/paragangliomas 4; Mitochondrial complex II deficiency, nuclear type 4	AD/AR	Biochemical; Cardiovascular; Oncologic	In conditions related to neoplasms, surveillance for and early diagnosis/treatment of associated neoplasms can be beneficial; In Mitochondrial complex II deficiency, nuclear type 4, medical management (eg, with riboflavin and coenzyme Q10) has been described, and individuals may have cardiac involvement such that surveillance may be beneficial	Biochemical; Cardiovascular; Neurologic; Oncologic	490809; 11404820; 12000816; 12213855; 12364472; 14500403; 15479192; 15328326; 14685938; 16317055; 17102084; 16522703; 17652212; 17848412; 17804857; 17200167; 18057081; 17667967; 18678321; 19251979; 19351833; 19576851; 20301715; 20503330; 21366490; 21565294; 21348866; 22328163; 22972948; 23322652; 26925370; 27604842; 32124427
The proof for causation related to Cowden syndrome is unclear

ClinVar

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

• Hereditary cancer-predisposing syndrome (555 variants)
• Pheochromocytoma;Gastrointestinal stromal tumor;Paragangliomas 4 (192 variants)
• not provided (191 variants)
• Gastrointestinal stromal tumor;Pheochromocytoma;Paragangliomas 4 (173 variants)
• Gastrointestinal stromal tumor;Paragangliomas 4;Pheochromocytoma (168 variants)
• Paragangliomas 4;Gastrointestinal stromal tumor;Pheochromocytoma (143 variants)
• Paragangliomas 4;Pheochromocytoma;Gastrointestinal stromal tumor (134 variants)
• Pheochromocytoma;Paragangliomas 4;Gastrointestinal stromal tumor (123 variants)
• Paragangliomas 4 (95 variants)
• Gastrointestinal stromal tumor (89 variants)
• Hereditary pheochromocytoma-paraganglioma (79 variants)
• not specified (77 variants)
• Carney-Stratakis syndrome (26 variants)
• Pheochromocytoma (17 variants)
• Cowden syndrome (12 variants)
• Mitochondrial complex 2 deficiency, nuclear type 4 (8 variants)
• SDHB-Related Disorders (5 variants)
• SDHB-related condition (5 variants)
• Inborn genetic diseases (3 variants)
• Ovarian cancer (3 variants)
• Carney-Stratakis syndrome;Paragangliomas 4;Pheochromocytoma (3 variants)
• Paraganglioma (3 variants)
• Pheochromocytoma;Carney-Stratakis syndrome;Paragangliomas 4 (3 variants)
• Gastrointestinal stromal tumor;Pheochromocytoma;Mitochondrial complex 2 deficiency, nuclear type 4;Carney-Stratakis syndrome;Paragangliomas 4 (2 variants)
• Mitochondrial complex 2 deficiency, nuclear type 4;Carney-Stratakis syndrome;Pheochromocytoma;Paragangliomas 4;Gastrointestinal stromal tumor (2 variants)
• Mitochondrial complex 2 deficiency, nuclear type 4;Carney-Stratakis syndrome;Paragangliomas 4;Pheochromocytoma;Gastrointestinal stromal tumor (2 variants)
• Carney triad (1 variants)
• Papillary renal cell carcinoma type 1 (1 variants)
• Carney-Stratakis syndrome;Pheochromocytoma;Paragangliomas 4 (1 variants)
• Paraganglioma;Pheochromocytoma (1 variants)
• Carney-Stratakis syndrome;Pheochromocytoma;Gastrointestinal stromal tumor;Paragangliomas 4;Mitochondrial complex 2 deficiency, nuclear type 4 (1 variants)
• Malignant tumor of breast (1 variants)
• Carney-Stratakis syndrome;Paragangliomas 4;Gastrointestinal stromal tumor;Mitochondrial complex 2 deficiency, nuclear type 4;Pheochromocytoma (1 variants)
• Pheochromocytoma;Paragangliomas 4;Carney-Stratakis syndrome (1 variants)
• Renal cell carcinoma (1 variants)
• Carney-Stratakis syndrome;Pheochromocytoma;Paragangliomas 4;Gastrointestinal stromal tumor;Cowden syndrome 1 (1 variants)
• bilateral breast cancer (1 variants)
• Von Hippel-Lindau syndrome (1 variants)
• Hereditary pheochromocytoma-paraganglioma;Gastrointestinal stromal tumor (1 variants)
• Mitochondrial complex II deficiency, nuclear type 1 (1 variants)
• Renal neoplasm (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SDHB 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			2	165	1	168
missense	14	53	453	3	1	524
nonsense	34	2	2			38
start loss	1	2				3
frameshift	61	10	1			72
inframe indel			5			5
splice donor/acceptor (+/-2bp)	15	17		1		33
splice region		3	40	47	2	92
non coding			10	121	23	154
Total	125	84	473	290	25

Highest pathogenic variant AF is 0.0000263

Variants in SDHB

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

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

Position	Type	Phenotype	Significance	ClinVar
1-17018721-CT-C			Benign (Mar 03, 2015)
1-17018748-A-G		Hereditary pheochromocytoma-paraganglioma • Carney-Stratakis syndrome	Uncertain significance (Jan 13, 2018)
1-17018779-T-C		Hereditary pheochromocytoma-paraganglioma • Carney-Stratakis syndrome	Uncertain significance (Jan 13, 2018)
1-17018851-G-A		not specified	Likely benign (Aug 15, 2023)
1-17018883-A-C		Hereditary cancer-predisposing syndrome • Paragangliomas 4;Gastrointestinal stromal tumor;Pheochromocytoma	Uncertain significance (Jan 05, 2023)
1-17018887-T-C		Gastrointestinal stromal tumor;Pheochromocytoma;Paragangliomas 4 • Hereditary cancer-predisposing syndrome	Likely benign (Dec 28, 2023)
1-17018887-T-G		Hereditary cancer-predisposing syndrome	Likely benign (Feb 20, 2024)
1-17018888-G-A		Hereditary cancer-predisposing syndrome	Uncertain significance (Jun 25, 2023)
1-17018888-GA-AG		Pheochromocytoma;Paragangliomas 4;Gastrointestinal stromal tumor • Hereditary cancer-predisposing syndrome	Uncertain significance (Jul 12, 2023)
1-17018889-A-C		Pheochromocytoma;Paragangliomas 4;Gastrointestinal stromal tumor	Uncertain significance (Oct 23, 2021)
1-17018889-A-G		Hereditary cancer-predisposing syndrome	Uncertain significance (Jun 25, 2023)
1-17018889-A-T		Gastrointestinal stromal tumor;Pheochromocytoma;Paragangliomas 4 • Hereditary cancer-predisposing syndrome • Hereditary pheochromocytoma-paraganglioma	Uncertain significance (Dec 02, 2023)
1-17018890-A-G		Hereditary cancer-predisposing syndrome	Likely benign (May 09, 2019)
1-17018891-G-A		Hereditary cancer-predisposing syndrome	Uncertain significance (May 26, 2023)
1-17018892-C-G		Gastrointestinal stromal tumor;Paragangliomas 4;Pheochromocytoma	Uncertain significance (May 07, 2022)
1-17018892-CT-C		Gastrointestinal stromal tumor;Paragangliomas 4;Pheochromocytoma • Hereditary cancer-predisposing syndrome	Uncertain significance (Apr 18, 2023)
1-17018896-C-T		Gastrointestinal stromal tumor;Paragangliomas 4;Pheochromocytoma • Hereditary cancer-predisposing syndrome	Likely benign (Oct 21, 2022)
1-17018898-TCTC-T		Paragangliomas 4;Gastrointestinal stromal tumor;Pheochromocytoma • Hereditary pheochromocytoma-paraganglioma	Uncertain significance (Apr 03, 2023)
1-17018899-C-T		Hereditary pheochromocytoma-paraganglioma	Likely benign (Feb 05, 2024)
1-17018900-T-A		Pheochromocytoma;Gastrointestinal stromal tumor;Paragangliomas 4	Uncertain significance (Jan 25, 2023)
1-17018900-T-G		Pheochromocytoma;Gastrointestinal stromal tumor;Paragangliomas 4	Uncertain significance (Nov 20, 2022)
1-17018902-C-A		Gastrointestinal stromal tumor	Uncertain significance (Jul 05, 2023)
1-17018903-T-A		Hereditary pheochromocytoma-paraganglioma • Hereditary cancer-predisposing syndrome	Uncertain significance (Jan 11, 2024)
1-17018904-T-C		Paragangliomas 4;Pheochromocytoma;Gastrointestinal stromal tumor • Gastrointestinal stromal tumor • Hereditary cancer-predisposing syndrome • Hereditary pheochromocytoma-paraganglioma	Uncertain significance (Dec 13, 2023)
1-17018905-A-G		Paragangliomas 4;Pheochromocytoma;Gastrointestinal stromal tumor • Hereditary cancer-predisposing syndrome	Likely benign (Mar 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SDHB	protein_coding	protein_coding	ENST00000375499	8	35449

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000244	0.984	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.102	158	154	1.02	0.00000823	1825
Missense in Polyphen		59	69.509	0.84881		811
Synonymous	0.0242	52	52.2	0.996	0.00000253	520
Loss of Function	2.13	9	19.0	0.473	0.00000124	196

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000160	0.000158
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Iron-sulfur protein (IP) 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: 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:11404820, ECO:0000269|PubMed:12000816, ECO:0000269|PubMed:12618761, ECO:0000269|PubMed:14500403, ECO:0000269|PubMed:14974914, ECO:0000269|PubMed:15328326, ECO:0000269|PubMed:17634472}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Paragangliomas 4 (PGL4) [MIM:115310]: 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:11404820, ECO:0000269|PubMed:11897817, ECO:0000269|PubMed:14715873, ECO:0000269|PubMed:14974914, ECO:0000269|PubMed:15328326}. 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: 0.636

Intolerance Scores

• loftool: 0.140
• rvis_EVS: 0.53
• rvis_percentile_EVS: 80.73

Haploinsufficiency Scores

• pHI: 0.405
• hipred: Y
• hipred_score: 0.694
• ghis: 0.429

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.987

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sdhb
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland 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); normal 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); renal/urinary system phenotype; neoplasm

Gene ontology

• Biological process: tricarboxylic acid cycle;succinate metabolic process;aerobic respiration;respiratory electron transport chain
• Cellular component: nucleoplasm;mitochondrion;mitochondrial inner membrane;mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone);plasma membrane;mitochondrial membrane
• Molecular function: protein binding;succinate dehydrogenase (ubiquinone) activity;electron transfer activity;metal ion binding;ubiquinone binding;2 iron, 2 sulfur cluster binding;3 iron, 4 sulfur cluster binding;4 iron, 4 sulfur cluster binding