SDHB succinate dehydrogenase complex iron sulfur subunit B [Homo sapiens (human)] - Gene

Summary

Official Symbol: SDHBprovided by HGNC
Official Full Name: succinate dehydrogenase complex iron sulfur subunit Bprovided by HGNC
Primary source: HGNC:HGNC:10681
See related: Ensembl:ENSG00000117118 MIM:185470; AllianceGenome:HGNC:10681
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: IP; SDH; CWS2; PGL4; SDH1; SDH2; PPGL4; SDHIP; MC2DN4
Summary: This tumor suppressor gene encodes the iron-sulfur protein subunit of the succinate dehydrogenase (SDH) enzyme complex which plays a critical role in mitochondria. The SDH enzyme complex is composed of four nuclear-encoded subunits. This enzyme complex converts succinate to fumarate which releases electrons as part of the citric acid cycle, and the enzyme complex additionally provides an attachment site for released electrons to be transferred to the oxidative phosphorylation pathway. The SDH enzyme complex plays a role in oxygen-related gene regulation through its conversion of succinate, which is an oxygen sensor that stabilizes the hypoxia-inducible factor 1 (HIF1) transcription factor. Sporadic and familial mutations in this gene result in paragangliomas, pheochromocytoma, and gastrointestinal stromal tumors, supporting a link between mitochondrial dysfunction and tumorigenesis. Mutations in this gene are also implicated in nuclear type 4 mitochondrial complex II deficiency. [provided by RefSeq, Jun 2022]
Expression: Ubiquitous expression in heart (RPKM 84.5), kidney (RPKM 76.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p36.13

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (17018722..17054032, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (16829151..16864469, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (17345217..17380527, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement.
Title: Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants: an international expert Consensus statement.
High rates of the SDHB p.Arg46Gln pathogenic variant predisposes New Zealand Maori to phaeochromocytoma/paraganglioma.
Title: High rates of the SDHB p.Arg46Gln pathogenic variant predisposes New Zealand Māori to phaeochromocytoma/paraganglioma.
Evidence for a Founder Effect of SDHB Exon 1 Deletion in Brazilian Patients With Paraganglioma.
Title: Evidence for a Founder Effect of SDHB Exon 1 Deletion in Brazilian Patients With Paraganglioma.
Distortion in transmission of pathogenic SDHB- and SDHD-mutated alleles from parent to offspring.
Title: Distortion in transmission of pathogenic SDHB- and SDHD-mutated alleles from parent to offspring.
Metabolic Characterization and Glyceraldehyde-3-Phosphate Dehydrogenase-Dependent Regulation of Epithelial Sodium Channels in hPheo1 Wild-type and SDHB Knockdown Cells.
Title: Metabolic Characterization and Glyceraldehyde-3-Phosphate Dehydrogenase-Dependent Regulation of Epithelial Sodium Channels in hPheo1 Wild-type and SDHB Knockdown Cells.
SDHB variant type impacts phenotype and malignancy in pheochromocytoma-paraganglioma.
Title: SDHB variant type impacts phenotype and malignancy in pheochromocytoma-paraganglioma.
Gastrointestinal stromal tumors caused by novel germline variants in SDHB and KIT: a report of two cases and literature review.
Title: Gastrointestinal stromal tumors caused by novel germline variants in SDHB and KIT: a report of two cases and literature review.
Succinate: A Serum Biomarker of SDHB-Mutated Paragangliomas and Pheochromocytomas.
Title: Succinate: A Serum Biomarker of SDHB-Mutated Paragangliomas and Pheochromocytomas.
LncRNA expression and SDHB mutations in pheochromocytomas and paragangliomas.
Title: LncRNA expression and SDHB mutations in pheochromocytomas and paragangliomas.
Increased expression of Nrf2 and elevated glucose uptake in pheochromocytoma and paraganglioma with SDHB gene mutation.
Title: Increased expression of Nrf2 and elevated glucose uptake in pheochromocytoma and paraganglioma with SDHB gene mutation.

Submit: New GeneRIF Correction See all GeneRIFs (193)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Professional guidelines

Description
Professional guideline ACMG 2013 The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in SDHB that are pathogenic or expected to be pathogenic. GuidelinePubMed

Associated conditions

Description	Tests
Carney-Stratakis syndrome MedGen: C1847319 OMIM: 606864 GeneReviews: Not available	Compare labs
Gastrointestinal stroma tumor MedGen: C0238198 OMIM: 606764 GeneReviews: Not available	Compare labs
Mitochondrial complex 2 deficiency, nuclear type 4 MedGen: C5543176 OMIM: 619224 GeneReviews: Not available	Compare labs
Paragangliomas 4 MedGen: C1861848 OMIM: 115310 GeneReviews: Hereditary Paraganglioma-Pheochromocytoma Syndromes	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-07-22) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-07-22) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
A genome-wide association study in 19 633 Japanese subjects identified LHX3-QSOX2 and IGF1 as adult height loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat downregulates succinate dehydrogenase complex, subunit B, iron sulfur (SDHB) expression in Jurkat T-cells	PubMed
	tat	Using a yeast two-hybrid system, HIV-1 Tat has been shown to bind the human succinate-ubiquinone oxidoreductase iron sulfur subunit, suggesting a role for this protein in mediating the biological activity of Tat during HIV-1 replication	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 2 iron, 2 sulfur cluster binding	ISS Inferred from Sequence or Structural Similarity more info
enables 3 iron, 4 sulfur cluster binding	ISS Inferred from Sequence or Structural Similarity more info
enables 4 iron, 4 sulfur cluster binding	ISS Inferred from Sequence or Structural Similarity more info
enables electron transfer activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables succinate dehydrogenase (quinone) activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables ubiquinone binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in aerobic respiration	IBA Inferred from Biological aspect of Ancestor more info
involved_in mitochondrial electron transport, succinate to ubiquinone	NAS Non-traceable Author Statement more info	PubMed
involved_in proton motive force-driven mitochondrial ATP synthesis	NAS Non-traceable Author Statement more info	PubMed
involved_in respiratory electron transport chain	IBA Inferred from Biological aspect of Ancestor more info
involved_in tricarboxylic acid cycle	IEA Inferred from Electronic Annotation more info
involved_in tricarboxylic acid cycle	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in mitochondrial inner membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in mitochondrial inner membrane	NAS Non-traceable Author Statement more info	PubMed
located_in mitochondrial inner membrane	TAS Traceable Author Statement more info
is_active_in mitochondrial membrane	IBA Inferred from Biological aspect of Ancestor more info
part_of mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone)	ISS Inferred from Sequence or Structural Similarity more info
part_of mitochondrial respiratory chain complex II, succinate dehydrogenase complex (ubiquinone)	NAS Non-traceable Author Statement more info	PubMed
located_in mitochondrion	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in plasma membrane	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial

Names: iron-sulfur subunit of complex II; succinate dehydrogenase complex, subunit B, iron sulfur (Ip)

NP_001394290.1

EC 1.3.5.1

NP_002991.2

EC 1.3.5.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_012340.1 RefSeqGene

Range

5001..40449

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_316

mRNA and Protein(s)

NM_001407361.1 → NP_001394290.1 succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial isoform 2

Status: REVIEWED

Source sequence(s)

AL049569
NM_003000.3 → NP_002991.2 succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial isoform 1 precursor

See identical proteins and their annotated locations for NP_002991.2

Status: REVIEWED

Source sequence(s)

BC007840, BF796275, BU554163

Consensus CDS

CCDS176.1

UniProtKB/Swiss-Prot

B2R545, P21912, Q0QEY7, Q9NQ12

UniProtKB/TrEMBL

A0A087WWT1

Related

ENSP00000364649.3, ENST00000375499.8

Conserved Domains (1) summary

PLN00129
Location:5 → 271

PLN00129; succinate dehydrogenase [ubiquinone] iron-sulfur subunit