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    ETFDH electron transfer flavoprotein dehydrogenase [ Homo sapiens (human) ]

    Gene ID: 2110, updated on 9-Dec-2024

    Summary

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    Official Symbol
    ETFDHprovided by HGNC
    Official Full Name
    electron transfer flavoprotein dehydrogenaseprovided by HGNC
    Primary source
    HGNC:HGNC:3483
    See related
    Ensembl:ENSG00000171503 MIM:231675; AllianceGenome:HGNC:3483
    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
    MADD; ETFQO
    Summary
    This gene encodes a component of the electron-transfer system in mitochondria and is essential for electron transfer from a number of mitochondrial flavin-containing dehydrogenases to the main respiratory chain. Mutations in this gene are associated with glutaric acidemia. Alternatively spliced transcript variants that encode distinct isoforms have been observed. [provided by RefSeq, Aug 2013]
    Expression
    Ubiquitous expression in liver (RPKM 42.8), duodenum (RPKM 28.5) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ETFDH in Genome Data Viewer
    Location:
    4q32.1
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (158672296..158709623)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (162023044..162060372)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (159593448..159630775)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124900802 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 22084 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr4:159461287-159462486 Neighboring gene relaxin family peptide receptor 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:159501162-159501738 Neighboring gene Sharpr-MPRA regulatory region 15067 Neighboring gene NANOG hESC enhancer GRCh37_chr4:159577538-159578061 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr4:159580614-159581120 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:159592018-159592654 Neighboring gene H3K27ac hESC enhancers GRCh37_chr4:159592655-159593291 and GRCh37_chr4:159593295-159593796 Neighboring gene small nucleolar RNA U3 Neighboring gene chromosome 4 open reading frame 46 Neighboring gene hESC enhancers GRCh37_chr4:159643958-159644541 and GRCh37_chr4:159644542-159645126 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15773 Neighboring gene H3K27ac hESC enhancer GRCh37_chr4:159690086-159690823 Neighboring gene peptidylprolyl isomerase D Neighboring gene Sharpr-MPRA regulatory region 12747 Neighboring gene RNA, U6 small nuclear 128, pseudogene Neighboring gene folliculin interacting protein 2 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr4:159766516-159767164 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:159802306-159803286 Neighboring gene Sharpr-MPRA regulatory region 14183 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:159823055-159823920 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr4:159823921-159824786 Neighboring gene uncharacterized LOC124900178 Neighboring gene sperm microtubule inner protein 2

    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. Late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD): case reports and epidemiology of ETFDH gene mutations. Chen W, et al. BMC Neurol, 2019 Dec 18. PMID 31852447, Free PMC Article
    2. Clinical features and ETFDH mutation spectrum in a cohort of 90 Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency. Xi J, et al. J Inherit Metab Dis, 2014 May. PMID 24357026
    3. The ETFDH c.158A>G variation disrupts the balanced interplay of ESE- and ESS-binding proteins thereby causing missplicing and multiple Acyl-CoA dehydrogenation deficiency. Olsen RK, et al. Hum Mutat, 2014 Jan. PMID 24123825
    4. Severe sensory neuropathy in patients with adult-onset multiple acyl-CoA dehydrogenase deficiency. Wang Z, et al. Neuromuscul Disord, 2016 Feb. PMID 26821934
    5. Significant clinical heterogeneity with similar ETFDH genotype in three Chinese patients with late-onset multiple acyl-CoA dehydrogenase deficiency. Fu HX, et al. Neurol Sci, 2016 Jul. PMID 27000805

    See all (58) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. ETFDH mutation involves excessive apoptosis and neurite outgrowth defect via Bcl2 pathway.
      Title: ETFDH mutation involves excessive apoptosis and neurite outgrowth defect via Bcl2 pathway.
    2. Multiple acyl-CoA dehydrogenase deficiency kills Mycobacterium tuberculosis in vitro and during infection.
      Title: Multiple acyl-CoA dehydrogenase deficiency kills Mycobacterium tuberculosis in vitro and during infection.
    3. Screening of multiple acyl-CoA dehydrogenase deficiency in newborns and follow-up of patients.
      Title: Screening of multiple acyl-CoA dehydrogenase deficiency in newborns and follow-up of patients.
    4. ETF dehydrogenase advances in molecular genetics and impact on treatment.
      Title: ETF dehydrogenase advances in molecular genetics and impact on treatment.
    5. Mitochondrial energetic impairment in a patient with late-onset glutaric acidemia Type 2.
      Title: Mitochondrial energetic impairment in a patient with late-onset glutaric acidemia Type 2.
    6. Clinical characteristics and gene mutation analysis of an adult patient with ETFDHrelated multiple acylCoA dehydrogenase deficiency.
      Title: Clinical characteristics and gene mutation analysis of an adult patient with ETFDH‑related multiple acyl‑CoA dehydrogenase deficiency.
    7. Molecular and Clinical Investigations on Portuguese Patients with Multiple acyl-CoA Dehydrogenase Deficiency.
      Title: Molecular and Clinical Investigations on Portuguese Patients with Multiple acyl-CoA Dehydrogenase Deficiency.
    8. the two variants of ETFDH gene identified probably underlie the pathogenesis of Glutaric acidemia type II in this family, and also enlarge ETFDH genotype-phenotype correlations spectrum.
      Title: A novel electron transfer flavoprotein dehydrogenase (ETFDH) gene mutation identified in a newborn with glutaric acidemia type II: a case report of a Chinese family.
    9. Low tumor expression of ETFDH was associated with a poorer overall survival in patients with hepatocellular carcinoma.
      Title: Expression and significance of ETFDH in hepatocellular carcinoma.
    10. A mutation is the most common EFTDH mutation in riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency and is most prevalent in China and South-East Asia where its epidemiology correlates with the distribution and migration patterns of the southern Min population in Southern China and neighbouring countries
      Title: Late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency (MADD): case reports and epidemiology of ETFDH gene mutations.
    Submit: New GeneRIF Correction See all GeneRIFs (33)

    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

    EBI GWAS Catalog

    Description
    A genome-wide perspective of genetic variation in human metabolism.
    EBI GWAS Catalog
    An atlas of genetic influences on human blood metabolites.
    EBI GWAS Catalog
    Human metabolic individuality in biomedical and pharmaceutical research.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    Clone Names

    • FLJ18477

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 4 iron, 4 sulfur cluster binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables electron transfer activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables electron-transferring-flavoprotein dehydrogenase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables electron-transferring-flavoprotein dehydrogenase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables electron-transferring-flavoprotein dehydrogenase activity TAS
    Traceable Author Statement
    more info
    		  
    enables flavin adenine dinucleotide binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables oxidoreductase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables quinone binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquinone binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in electron transport chain IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in electron transport chain IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in fatty acid beta-oxidation using acyl-CoA dehydrogenase IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in respiratory electron transport chain TAS
    Traceable Author Statement
    more info
    		  
    involved_in response to oxidative stress ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    is_active_in mitochondrial inner membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrial inner membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrial membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion HTP PubMed 

    General protein information

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    Preferred Names
    electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial
    Names
    ETF dehydrogenase
    ETF-QO
    ETF-ubiquinone oxidoreductase
    electron-transferring-flavoprotein dehydrogenase
    mutant electron transfer flavoprotein dehydrogenase
    NP_001268666.1
    NP_001268667.1
    NP_004444.2

    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_007078.2 RefSeqGene

      Range
      4955..42282
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001281737.2 → NP_001268666.1  electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an an alternate in-frame exon in the 5' coding region compared to variant 1. The resulting protein (isoform 2) is shorter but has the same N- and C-termini compared to isoform 1.
      Source sequence(s)
      AC107219, AK293737, AK304838, DA798232
      Consensus CDS
      CCDS64090.1
      UniProtKB/TrEMBL
      Q547S8
      Related
      ENSP00000303552.5, ENST00000307738.5
      Conserved Domains (3) summary
      COG0644
      Location:20 → 482
      FixC; Dehydrogenase (flavoprotein) [Energy production and conversion]
      pfam05187
      Location:465 → 568
      ETF_QO; Electron transfer flavoprotein-ubiquinone oxidoreductase, 4Fe-4S
      cl21454
      Location:21 → 170
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    2. NM_001281738.1 → NP_001268667.1  electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial isoform 3

      See identical proteins and their annotated locations for NP_001268667.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) represents use of an alternate promoter, differs in the 5' UTR, and uses a downstream start codon compared to variant 1. The resulting protein (isoform 3) is shorter and has a distinct N-terminus compared to isoform 1.
      Source sequence(s)
      AK293737, DB221748
      Consensus CDS
      CCDS93661.1
      UniProtKB/TrEMBL
      B4DEQ0, Q547S8
      Related
      ENSP00000508043.1, ENST00000683305.1
      Conserved Domains (2) summary
      COG0644
      Location:6 → 468
      FixC; Dehydrogenase (flavoprotein) [Energy production and conversion]
      pfam05187
      Location:451 → 554
      ETF_QO; Electron transfer flavoprotein-ubiquinone oxidoreductase, 4Fe-4S

    3. NM_004453.4 → NP_004444.2  electron transfer flavoprotein-ubiquinone oxidoreductase, mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_004444.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest protein (isoform 1).
      Source sequence(s)
      AC107219, AK293737, BC011890, BX957055, DA798232
      Consensus CDS
      CCDS3800.1
      UniProtKB/Swiss-Prot
      B4E3R9, J3KND9, Q16134, Q7Z347
      UniProtKB/TrEMBL
      A0A2I6U1K5, A0A2I6U1Q3, Q547S8
      Related
      ENSP00000426638.1, ENST00000511912.6
      Conserved Domains (3) summary
      COG0644
      Location:67 → 529
      FixC; Dehydrogenase (flavoprotein) [Energy production and conversion]
      pfam05187
      Location:512 → 615
      ETF_QO; Electron transfer flavoprotein-ubiquinone oxidoreductase, 4Fe-4S
      cl21454
      Location:68 → 217
      NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins

    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_000004.12 Reference GRCh38.p14 Primary Assembly

      Range
      158672296..158709623
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      162023044..162060372
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q16134.2 GenPept UniProtKB/Swiss-Prot:Q16134

    Gene LinkOut

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

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