SDHD succinate dehydrogenase complex subunit D [Homo sapiens (human)] - Gene

Summary

Official Symbol: SDHDprovided by HGNC
Official Full Name: succinate dehydrogenase complex subunit Dprovided by HGNC
Primary source: HGNC:HGNC:10683
See related: Ensembl:ENSG00000204370 MIM:602690; AllianceGenome:HGNC:10683
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: PGL; CBT1; CWS3; PGL1; QPs3; SDH4; cybS; CII-4; PPGL1; MC2DN3
Summary: This gene encodes a member of complex II of the respiratory chain, which is responsible for the oxidation of succinate. The encoded protein is one of two integral membrane proteins anchoring the complex to the matrix side of the mitochondrial inner membrane. Mutations in this gene are associated with the formation of tumors, including hereditary paraganglioma. Transmission of disease occurs almost exclusively through the paternal allele, suggesting that this locus may be maternally imprinted. There are pseudogenes for this gene on chromosomes 1, 2, 3, 7, and 18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]
Expression: Ubiquitous expression in kidney (RPKM 95.3), duodenum (RPKM 84.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q23.1

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (112086873..112095794)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (112097127..112106049)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (111957597..111966518)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

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?

Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants.
Title: Clinical consensus guideline on the management of phaeochromocytoma and paraganglioma in patients harbouring germline SDHD pathogenic variants.
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.
A need to tailor surveillance based on family history: describing a highly penetrant familial paraganglioma kindred with an SDHD pathogenic variant.
Title: A need to tailor surveillance based on family history: describing a highly penetrant familial paraganglioma kindred with an SDHD pathogenic variant.
The SDHD:p.H102R Variant Is Frequent in Russian Patients with Head and Neck Paragangliomas and Associated with Loss of 11p15.5 Region and Hypermethylation of H19-DMR.
Title: The SDHD:p.H102R Variant Is Frequent in Russian Patients with Head and Neck Paragangliomas and Associated with Loss of 11p15.5 Region and Hypermethylation of H19-DMR.
Consolidating biallelic SDHD variants as a cause of mitochondrial complex II deficiency.
Title: Consolidating biallelic SDHD variants as a cause of mitochondrial complex II deficiency.
Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHB and SDHD.
Title: Quantifying evidence toward pathogenicity for rare phenotypes: The case of succinate dehydrogenase genes, SDHB and SDHD.
Characteristics of germline mutations in Korean patients with pheochromocytoma/paraganglioma.
Title: Characteristics of germline mutations in Korean patients with pheochromocytoma/paraganglioma.
MicroRNA-101-3p Modulates Mitochondrial Metabolism via the Regulation of Complex II Assembly.
Title: MicroRNA-101-3p Modulates Mitochondrial Metabolism via the Regulation of Complex II Assembly.
Complex II subunit SDHD is critical for cell growth and metabolism, which can be partially restored with a synthetic ubiquinone analog.
Title: Complex II subunit SDHD is critical for cell growth and metabolism, which can be partially restored with a synthetic ubiquinone analog.
Bcl2l10 induces metabolic alterations in ovarian cancer cells by regulating the TCA cycle enzymes SDHD and IDH1.
Title: Bcl2l10 induces metabolic alterations in ovarian cancer cells by regulating the TCA cycle enzymes SDHD and IDH1.

Submit: New GeneRIF Correction See all GeneRIFs (119)

Phenotypes

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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 SDHD that are pathogenic or expected to be pathogenic. GuidelinePubMed

Associated conditions

Description	Tests
Carney-Stratakis syndrome MedGen: C1847319 OMIM: 606864 GeneReviews: Not available	not available
Mitochondrial complex 2 deficiency, nuclear type 3 MedGen: C5436934 OMIM: 619167 GeneReviews: Not available	not available
Paragangliomas 1 MedGen: C3494181 OMIM: 168000 GeneReviews: Hereditary Paraganglioma-Pheochromocytoma Syndromes	not available

Copy number response

Description
Copy number response Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2021-08-11) ClinGen Genome Curation PagePubMed Triplosensitivity No evidence available (Last evaluated 2021-08-11) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2246E (e-PCR)
- UniSTS:151407

RH80714 (e-PCR)
- UniSTS:91505

RH64925 (e-PCR)
- UniSTS:49069

A002R25 (e-PCR)
- UniSTS:56503

WI-11979 (e-PCR)
- UniSTS:80122

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables electron transfer activity	TAS Traceable Author Statement more info	PubMed
enables heme binding	IBA Inferred from Biological aspect of Ancestor more info
enables heme binding	ISS Inferred from Sequence or Structural Similarity 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	IEA Inferred from Electronic Annotation more info
enables ubiquinone binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquinone binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in cellular response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in mitochondrial electron transport, succinate to ubiquinone	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 regulation of catecholamine secretion	IEA Inferred from Electronic Annotation more info
involved_in tricarboxylic acid cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in tricarboxylic acid cycle	IDA Inferred from Direct Assay more info	PubMed
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 envelope	TAS Traceable Author Statement more info	PubMed
located_in mitochondrial inner membrane	IDA Inferred from Direct Assay more info	PubMed
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
located_in mitochondrion	HTP more info	PubMed
part_of respiratory chain complex II (succinate dehydrogenase)	IBA Inferred from Biological aspect of Ancestor more info
part_of respiratory chain complex II (succinate dehydrogenase)	IDA Inferred from Direct Assay more info	PubMed
part_of respiratory chain complex II (succinate dehydrogenase)	ISS Inferred from Sequence or Structural Similarity more info
part_of respiratory chain complex II (succinate dehydrogenase)	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial

Names: malate dehydrogenase [quinone] cytochrome b small subunit; succinate dehydrogenase complex subunit D integral membrane protein; succinate-ubiquinone oxidoreductase cytochrome b small subunit; succinate-ubiquinone reductase membrane anchor subunit

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_012337.3 RefSeqGene

Range

5027..13948

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_9

mRNA and Protein(s)

NM_001276503.2 → NP_001263432.1 succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial isoform b precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate coding exon, which results in a frameshift, compared to variant 1. The encoded isoform (b) is shorter and has a distinct C-terminus, compared to isoform a.

Source sequence(s)

AI753083, AP002007, BC015188, BQ932668, CD105572

Consensus CDS

CCDS60959.1

UniProtKB/TrEMBL

A0A0S2Z4H7

Related

ENSP00000436217.1, ENST00000528048.5
NM_001276504.2 → NP_001263433.1 succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial isoform c precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate coding exon, but retains the reading frame, compared to variant 1. The encoded isoform (c) is shorter than isoform a.

Source sequence(s)

AI753083, AP002007, BC015188, BF211358, BQ932668

Consensus CDS

CCDS60960.1

UniProtKB/Swiss-Prot

O14521

Related

ENSP00000436669.1, ENST00000525291.5

Conserved Domains (1) summary

cd03496
Location:21 → 119

SQR_TypeC_CybS; SQR catalyzes the oxidation of succinate to fumarate coupled to the reduction of quinone to quinol. Eukaryotic SQRs reduce high potential quinones such as ubiquinone. SQR is also called succinate dehydrogenase or Complex II, and is part of the citric ...
NM_001276506.2 → NP_001263435.1 succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial isoform d precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternate coding exon, which results in a frameshift, compared to variant 1. The encoded isoform (d) is shorter and has a distinct C-terminus, compared to isoform a.

Source sequence(s)

AI753083, AP002007, BC015188, BG492859, BQ932668

Consensus CDS

CCDS60958.1

UniProtKB/Swiss-Prot

O14521

Related

ENSP00000432005.1, ENST00000526592.5

Conserved Domains (1) summary

cl00881
Location:60 → 105

SQR_QFR_TM; Succinate:quinone oxidoreductase (SQR) and Quinol:fumarate reductase (QFR) family, transmembrane subunits; SQR catalyzes the oxidation of succinate to fumarate coupled to the reduction of quinone to quinol, while QFR catalyzes the reverse reaction. SQR, ...
NM_003002.4 → NP_002993.1 succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial isoform a precursor

See identical proteins and their annotated locations for NP_002993.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a).

Source sequence(s)

AI753083, AP002007, BC015188

Consensus CDS

CCDS31678.1

UniProtKB/Swiss-Prot

A6ND90, B3KQQ8, E9PIC0, E9PIG3, E9PQI9, O14521, Q53XW5, Q6IRW2

UniProtKB/TrEMBL

A0A0S2Z4J3

Related

ENSP00000364699.3, ENST00000375549.8

Conserved Domains (1) summary

cd03496
Location:60 → 158

SQR_TypeC_CybS; SQR catalyzes the oxidation of succinate to fumarate coupled to the reduction of quinone to quinol. Eukaryotic SQRs reduce high potential quinones such as ubiquinone. SQR is also called succinate dehydrogenase or Complex II, and is part of the citric ...

RNA

NR_077060.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) contains an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AI753083, AP002007, BC015188, BE567994, BQ932668

Related

ENST00000714090.1