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    SDHA succinate dehydrogenase complex flavoprotein subunit A [ Homo sapiens (human) ]

    Gene ID: 6389, updated on 10-Dec-2024

    Summary

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    Official Symbol
    SDHAprovided by HGNC
    Official Full Name
    succinate dehydrogenase complex flavoprotein subunit Aprovided by HGNC
    Primary source
    HGNC:HGNC:10680
    See related
    Ensembl:ENSG00000073578 MIM:600857; AllianceGenome:HGNC:10680
    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
    FP; PGL5; SDH1; SDH2; SDHF; PPGL5; CMD1GG; MC2DN1; NDAXOA
    Summary
    This gene encodes a major catalytic subunit of succinate-ubiquinone oxidoreductase, a complex of the mitochondrial respiratory chain. The complex is composed of four nuclear-encoded subunits and is localized in the mitochondrial inner membrane. Mutations in this gene have been associated with a form of mitochondrial respiratory chain deficiency known as Leigh Syndrome. A pseudogene has been identified on chromosome 3q29. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]
    Expression
    Ubiquitous expression in heart (RPKM 63.7), kidney (RPKM 34.3) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SDHA in Genome Data Viewer
    Location:
    5p15.33
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (218320..268746)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (209363..254841)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (218435..257197)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124900929 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:207882-208207 Neighboring gene leucine rich repeat containing 14B Neighboring gene coiled-coil domain containing 127 Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:218445-219253 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:270110-270802 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22271 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15861 Neighboring gene PDCD6-AHRR readthrough (NMD candidate) Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:278988-279488 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:279489-279989 Neighboring gene PDCD6 divergent transcript Neighboring gene programmed cell death 6 Neighboring gene PPP4R2 pseudogene 1

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. Homozygous Gly555Glu mutation in the nuclear-encoded 70 kDa flavoprotein gene causes instability of the respiratory chain complex II. Van Coster R, et al. Am J Med Genet A, 2003 Jul 1. PMID 12794685
    2. SDHA loss-of-function mutations in KIT-PDGFRA wild-type gastrointestinal stromal tumors identified by massively parallel sequencing. Pantaleo MA, et al. J Natl Cancer Inst, 2011 Jun 22. PMID 21505157
    3. SDHA mutated paragangliomas may be at high risk of metastasis. Tufton N, et al. Endocr Relat Cancer, 2017 Jul. PMID 28500238
    4. Somatic SDHA mutations in paragangliomas in siblings: Case report of 2 cases. Huang YC, et al. Medicine (Baltimore), 2020 Oct 9. PMID 33031286, Free PMC Article
    5. Familial neonatal isolated cardiomyopathy caused by a mutation in the flavoprotein subunit of succinate dehydrogenase. Levitas A, et al. Eur J Hum Genet, 2010 Oct. PMID 20551992, Free PMC Article

    See all (250) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. SDHA-related phaeochromocytoma and paraganglioma: review and clinical management.
      Title: SDHA-related phaeochromocytoma and paraganglioma: review and clinical management.
    2. Succinate dehydrogenase A deficient renal cell carcinoma: A rare renal tumor distinct from typical Succinate dehydrogenase deficient renal cell carcinoma.
      Title: Succinate dehydrogenase A deficient renal cell carcinoma: A rare renal tumor distinct from typical Succinate dehydrogenase deficient renal cell carcinoma.
    3. SDHA Germline Mutations in SDH-Deficient GISTs: A Current Update.
      Title: SDHA Germline Mutations in SDH-Deficient GISTs: A Current Update.
    4. PIKE-A Modulates Mitochondrial Metabolism through Increasing SDHA Expression Mediated by STAT3/FTO Axis.
      Title: PIKE-A Modulates Mitochondrial Metabolism through Increasing SDHA Expression Mediated by STAT3/FTO Axis.
    5. Upregulation of SDHA inhibited proliferation, migration, and invasion of clear cell renal cell carcinoma cells via inactivation of the Wnt/beta-catenin pathway.
      Title: Upregulation of SDHA inhibited proliferation, migration, and invasion of clear cell renal cell carcinoma cells via inactivation of the Wnt/β-catenin pathway.
    6. Subcellular Proteome Analysis Reveals Apoptotic Vulnerability of T-Cell Acute Lymphoblastic Leukemia.
      Title: Subcellular Proteome Analysis Reveals Apoptotic Vulnerability of T-Cell Acute Lymphoblastic Leukemia.
    7. Familial wild-type gastrointestinal stromal tumour in association with germline truncating variants in both SDHA and PALB2.
      Title: Familial wild-type gastrointestinal stromal tumour in association with germline truncating variants in both SDHA and PALB2.
    8. A novel de novo heterozygous pathogenic variant in the SDHA gene results in childhood onset bilateral optic atrophy and cognitive impairment.
      Title: A novel de novo heterozygous pathogenic variant in the SDHA gene results in childhood onset bilateral optic atrophy and cognitive impairment.
    9. Whole Exome Sequencing Identifies Novel Genetic Alterations in Patients with Pheochromocytoma/Paraganglioma.
      Title: Whole Exome Sequencing Identifies Novel Genetic Alterations in Patients with Pheochromocytoma/Paraganglioma.
    10. Single nucleotide variants of succinate dehydrogenase A gene in renal cell carcinoma.
      Title: Single nucleotide variants of succinate dehydrogenase A gene in renal cell carcinoma.
    Submit: New GeneRIF Correction See all GeneRIFs (64)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Dilated cardiomyopathy 1GG
    MedGen: C3150898 OMIM: 613642 GeneReviews: Not available
    		not available
    Mitochondrial complex II deficiency, nuclear type 1
    MedGen: C5700310 OMIM: 252011 GeneReviews: Not available
    		not available
    Neurodegeneration with ataxia and late-onset optic atrophy
    MedGen: C5543254 OMIM: 619259 GeneReviews: Not available
    		not available
    Paragangliomas 5
    MedGen: C3279992 OMIM: 614165 GeneReviews: Hereditary Paraganglioma-Pheochromocytoma Syndromes
    		not available

    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
    Nef nef HIV-1 Nef is identified to have a physical interaction with succinate dehydrogenase complex, subunit A, flavoprotein (SDHA) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    Vpr vpr A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies downregulation of succinate dehydrogenase complex, subunit A (SDHA) expression by HIV-1 Vpr in Vpr transduced macrophages PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables electron transfer activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables flavin adenine dinucleotide binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables succinate dehydrogenase (quinone) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    contributes_to succinate dehydrogenase (quinone) activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables succinate dehydrogenase (quinone) activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    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 nervous system development IMP
    Inferred from Mutant Phenotype
    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in succinate metabolic process 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 
    involved_in tricarboxylic acid cycle TAS
    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 matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		  
    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] flavoprotein subunit, mitochondrial
    Names
    flavoprotein subunit of complex II
    malate dehydrogenase [quinone] flavoprotein subunit
    succinate dehydrogenase complex, subunit A, flavoprotein (Fp)
    NP_001281261.1
    NP_001317687.1
    NP_004159.2
    XP_011512374.1
    XP_011512375.1
    XP_047273423.1
    XP_054209018.1
    XP_054209019.1
    XP_054209020.1

    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

    1. NG_012339.1 RefSeqGene

      Range
      5080..43842
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_315

    mRNA and Protein(s)

    1. NM_001294332.2 → NP_001281261.1  succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon in the 5' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AC021087, AK291311, AK295937, DA160919, HY265959
      Consensus CDS
      CCDS77992.1
      UniProtKB/TrEMBL
      Q0QF12
      Related
      ENSP00000427703.1, ENST00000510361.5
      Conserved Domains (3) summary
      PTZ00139
      Location:40 → 616
      PTZ00139; Succinate dehydrogenase [ubiquinone] flavoprotein subunit; Provisional
      pfam02910
      Location:467 → 616
      Succ_DH_flav_C; Fumarate reductase flavoprotein C-term
      cl21454
      Location:104 → 423
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    2. NM_001330758.2 → NP_001317687.1  succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks two in-frame exons in the 3' coding region, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
      Source sequence(s)
      AC021087
      Consensus CDS
      CCDS82985.1
      UniProtKB/TrEMBL
      D6RFM5
      Related
      ENSP00000426514.1, ENST00000504309.5
      Conserved Domains (3) summary
      PTZ00139
      Location:40 → 583
      PTZ00139; Succinate dehydrogenase [ubiquinone] flavoprotein subunit; Provisional
      pfam02910
      Location:539 → 583
      Succ_DH_flav_C; Fumarate reductase flavoprotein C-term
      cl21454
      Location:85 → 471
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    3. NM_004168.4 → NP_004159.2  succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial isoform 1

      See identical proteins and their annotated locations for NP_004159.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC021087, AK291311, BC001380, DA160919, HY265959
      Consensus CDS
      CCDS3853.1
      UniProtKB/Swiss-Prot
      A8K5J6, B4DJ60, E9PBJ5, P31040, Q16395, Q59GW8, Q8IW48, Q9UMY5
      UniProtKB/TrEMBL
      Q0QF12
      Related
      ENSP00000264932.6, ENST00000264932.11
      Conserved Domains (1) summary
      PTZ00139
      Location:40 → 664
      PTZ00139; Succinate dehydrogenase [ubiquinone] flavoprotein subunit; Provisional

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      218320..268746
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011514072.3 → XP_011512374.1  succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial isoform X1

      UniProtKB/TrEMBL
      Q0QF12
      Conserved Domains (3) summary
      PTZ00139
      Location:40 → 636
      PTZ00139; Succinate dehydrogenase [ubiquinone] flavoprotein subunit; Provisional
      pfam02910
      Location:515 → 635
      Succ_DH_flav_C; Fumarate reductase flavoprotein C-term
      cl21454
      Location:85 → 471
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    2. XM_011514073.3 → XP_011512375.1  succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial isoform X3

      Conserved Domains (2) summary
      TIGR01816
      Location:80 → 555
      sdhA_forward; succinate dehydrogenase, flavoprotein subunit, E. coli/mitochondrial subgroup
      cl21454
      Location:85 → 471
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    3. XM_047417467.1 → XP_047273423.1  succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial isoform X2

      UniProtKB/TrEMBL
      B4DYN5

    RNA

    1. XR_007058614.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      209363..254841
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054353043.1 → XP_054209018.1  succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial isoform X1

      UniProtKB/TrEMBL
      Q0QF12

    2. XM_054353045.1 → XP_054209020.1  succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial isoform X3

    3. XM_054353044.1 → XP_054209019.1  succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial isoform X2

      UniProtKB/TrEMBL
      B4DYN5
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P31040.2 GenPept UniProtKB/Swiss-Prot:P31040

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