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    SDHAF2 succinate dehydrogenase complex assembly factor 2 [ Homo sapiens (human) ]

    Gene ID: 54949, updated on 5-Mar-2024

    Summary

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    Official Symbol
    SDHAF2provided by HGNC
    Official Full Name
    succinate dehydrogenase complex assembly factor 2provided by HGNC
    Primary source
    HGNC:HGNC:26034
    See related
    Ensembl:ENSG00000167985 MIM:613019; AllianceGenome:HGNC:26034
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PGL2; SDH5; PPGL2; hSDH5; C11orf79
    Summary
    This gene encodes a mitochondrial assembly factor needed for the flavination of a succinate dehydrogenase complex subunit (SDHA), which is required for activity of the succinate dehydrogenase complex. Mutations in this gene are associated with paraganglioma. [provided by RefSeq, May 2022]
    Expression
    Ubiquitous expression in lymph node (RPKM 19.3), adrenal (RPKM 17.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    11q12.2
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (61430124..61446733)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (61419022..61435631)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (61197596..61214205)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:61159824-61160785 Neighboring gene transmembrane protein 216 Neighboring gene cleavage and polyadenylation specific factor 7 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:61196662-61197310 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:61197385-61197720 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:61213814-61214561 Neighboring gene RNA, 7SL, cytoplasmic 23, pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr11:61225919-61226100 Neighboring gene Sharpr-MPRA regulatory region 8840 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:61253575-61254394 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:61255818-61256485 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:61256486-61257152 Neighboring gene stabilizer of axonemal microtubules 4 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:61261837-61262435 Neighboring gene uncharacterized LOC105369329 Neighboring gene MPRA-validated peak1286 silencer

    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. An overview of 20 years of genetic studies in pheochromocytoma and paraganglioma. Buffet A, et al. Best Pract Res Clin Endocrinol Metab, 2020 Mar. PMID 32295730
    2. A Family With a Carotid Body Paraganglioma and Thyroid Neoplasias With a New SDHAF2 Germline Variant. Wolf KI, et al. J Endocr Soc, 2019 Nov 1. PMID 31687641, Free PMC Article
    3. PHEOCHROMOCYTOMA: A GENETIC AND DIAGNOSTIC UPDATE. Mercado-Asis LB, et al. Endocr Pract, 2018 Jan. PMID 29144820
    4. Germline mutations and genotype-phenotype associations in head and neck paraganglioma patients with negative family history in China. Zhu WD, et al. Eur J Med Genet, 2015 Sep. PMID 26096992
    5. Universal genetic screening uncovers a novel presentation of an SDHAF2 mutation. Casey R, et al. J Clin Endocrinol Metab, 2014 Jul. PMID 24712571

    See all (46) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The roles of SDHAF2 and dicarboxylate in covalent flavinylation of SDHA, the human complex II flavoprotein.
      Title: The roles of SDHAF2 and dicarboxylate in covalent flavinylation of SDHA, the human complex II flavoprotein.
    2. SDH5 Depletion Enhances Radiosensitivity by Regulating p53: A New Method for Noninvasive Prediction of Radiotherapy Response.
      Title: SDH5 Depletion Enhances Radiosensitivity by Regulating p53: A New Method for Noninvasive Prediction of Radiotherapy Response.
    3. Loss of SDHAF2 gene is associated with paragangliomas.
      Title: Loss of maternal chromosome 11 is a signature event in SDHAF2, SDHD, and VHL-related paragangliomas, but less significant in SDHB-related paragangliomas.
    4. The SDHA, TMEM127, MAX, and SDHAF2 genes contribute to hereditary pheochromocytoma and paraganglioma.
      Title: Clinical Characterization of the Pheochromocytoma and Paraganglioma Susceptibility Genes SDHA, TMEM127, MAX, and SDHAF2 for Gene-Informed Prevention.
    5. data show that SDHA flavination is independent of SDHAF2 in breast cancer cells, employing an alternative mechanism.
      Title: The Assembly Factor SDHAF2 Is Dispensable for Flavination of the Catalytic Subunit of Mitochondrial Complex II in Breast Cancer Cells.
    6. FAD interacts noncovalently with SDHA in the absence of SDH5
      Title: In-vitro, SDH5-dependent flavinylation of immobilized human respiratory complex II flavoprotein.
    7. Autosomal dominant susceptibility for Paraganglioma is modified by imprinting and mutations in the SDHAF2 gene cause Paragangliomas only when the mutation is inherited from father.
      Title: A two-decade experience of head and neck paragangliomas in a whole population-based single centre cohort.
    8. Loss of heterozygosity was found in more than 50 % of the von Hippel-Lindau-associated pheochromocytomas, and was correlated with a significant decrease (p < 0.05) in both SDHAF2 and SDHD mRNA expression, which may be suggestive of a pathogenic role.
      Title: Role of SDHAF2 and SDHD in von Hippel-Lindau associated pheochromocytomas.
    9. New mutation found in SDHAF2 gene in pheochromocytoma/paraganglioma patients.
      Title: Universal genetic screening uncovers a novel presentation of an SDHAF2 mutation.
    10. Data indicate that SDH5 is protected from mitochondrial LON (LONM)-mediated degradation in mitochondria by its stable interaction with SDHA, a state that is dysregulated in hereditary paraganglioma 2 (PGL2).
      Title: Mitochondrial matrix proteostasis is linked to hereditary paraganglioma: LON-mediated turnover of the human flavinylation factor SDH5 is regulated by its interaction with SDHA.
    Submit: New GeneRIF Correction See all GeneRIFs (18)

    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 SDHAF2 that are pathogenic or expected to be pathogenic.

    GuidelinePubMed

    Associated conditions

    Description Tests
    Paragangliomas 2
    MedGen: C1866552 OMIM: 601650 GeneReviews: Hereditary Paraganglioma-Pheochromocytoma Syndromes
    		Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2022-05-11)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2022-05-11)

    ClinGen Genome Curation PagePubMed

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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

    Potential readthrough

    Included gene: SAXO4

    Homology

    Clone Names

    • FLJ20487

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    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 IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in mitochondrial respiratory chain complex II assembly IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    acts_upstream_of_or_within negative regulation of canonical Wnt signaling pathway IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    acts_upstream_of_or_within negative regulation of epithelial to mesenchymal transition IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within protein dephosphorylation IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    involved_in protein-FAD linkage IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein-FAD linkage IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in tricarboxylic acid cycle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in mitochondrial matrix IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    succinate dehydrogenase assembly factor 2, mitochondrial
    Names
    SDH assembly factor 2
    succinate dehydrogenase subunit 5, mitochondrial

    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_023393.1 RefSeqGene

      Range
      5001..21643
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_519

    mRNA and Protein(s)

    1. NM_017841.4 → NP_060311.1  succinate dehydrogenase assembly factor 2, mitochondrial

      See identical proteins and their annotated locations for NP_060311.1

      Status: VALIDATED

      Source sequence(s)
      AP003108
      Consensus CDS
      CCDS8007.1
      UniProtKB/Swiss-Prot
      Q9NX18
      Related
      ENSP00000301761.3, ENST00000301761.7
      Conserved Domains (1) summary
      pfam03937
      Location:67 → 140
      Sdh5; Flavinator of succinate dehydrogenase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      61430124..61446733
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      61419022..61435631
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NX18.1 GenPept UniProtKB/Swiss-Prot:Q9NX18

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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