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    ADH4 alcohol dehydrogenase 4 (class II), pi polypeptide [ Homo sapiens (human) ]

    Gene ID: 127, updated on 2-Nov-2024

    Summary

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    Official Symbol
    ADH4provided by HGNC
    Official Full Name
    alcohol dehydrogenase 4 (class II), pi polypeptideprovided by HGNC
    Primary source
    HGNC:HGNC:252
    See related
    Ensembl:ENSG00000198099 MIM:103740; AllianceGenome:HGNC:252
    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
    ADH-2; HEL-S-4
    Summary
    This gene encodes class II alcohol dehydrogenase 4 pi subunit, which is a member of the alcohol dehydrogenase family. Members of this enzyme family metabolize a wide variety of substrates, including ethanol, retinol, other aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. Class II alcohol dehydrogenase is a homodimer composed of 2 pi subunits. It exhibits a high activity for oxidation of long-chain aliphatic alcohols and aromatic alcohols and is less sensitive to pyrazole. This gene is localized to chromosome 4 in the cluster of alcohol dehydrogenase genes. [provided by RefSeq, Jul 2008]
    Expression
    Restricted expression toward liver (RPKM 940.8) See more
    Orthologs
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    Genomic context

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    See ADH4 in Genome Data Viewer
    Location:
    4q23
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 4 NC_000004.12 (99123658..99144297, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 4 NC_060928.1 (102438693..102459340, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (100044809..100065448, complement)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene ADH5 promoter Neighboring gene uncharacterized LOC100507053 Neighboring gene alcohol dehydrogenase 5 (class III), chi polypeptide Neighboring gene Sharpr-MPRA regulatory region 12553 Neighboring gene uncharacterized LOC124900739 Neighboring gene ADH4 promoter Neighboring gene 4E3 enhancer upstream of ADH4 Neighboring gene proliferating cell nuclear antigen pseudogene 1 Neighboring gene proliferating cell nuclear antigen pseudogene 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 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. Recessive genetic mode of an ADH4 variant in substance dependence in African-Americans: A model of utility of the HWD test. Luo X, et al. Behav Brain Funct, 2008 Sep 18. PMID 18801187, Free PMC Article
    2. The alcohol dehydrogenase system. Jörnvall H. EXS, 1994. PMID 8032153
    3. Structure of the class II enzyme of human liver alcohol dehydrogenase: combined cDNA and protein sequence determination of the pi subunit. Höög JO, et al. Biochemistry, 1987 Apr 7. PMID 3036213
    4. ADH4 intronic variations are associated with alcohol dependence: results from an Italian case-control association study. Turchi C, et al. Pharmacogenet Genomics, 2012 Feb. PMID 22044940
    5. Identification of ADH4 as a novel and potential prognostic marker in hepatocellular carcinoma. Wei RR, et al. Med Oncol, 2012 Dec. PMID 22147505

    See all (73) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Novel Insights into MEG3/miR664a-3p/ADH4 Axis and Its Possible Role in Hepatocellular Carcinoma from an in Silico Perspective.
      Title: Novel Insights into MEG3/miR664a-3p/ADH4 Axis and Its Possible Role in Hepatocellular Carcinoma from an in Silico Perspective.
    2. No significant association between SNPs in the CLOCK and ADH4 genes and susceptibility to cluster headaches: A systematic review and meta-analysis.
      Title: No significant association between SNPs in the CLOCK and ADH4 genes and susceptibility to cluster headaches: A systematic review and meta-analysis.
    3. A novel mechanism underlying alcohol dehydrogenase expression: hsa-miR-148a-3p promotes ADH4 expression via an AGO1-dependent manner in control and ethanol-exposed hepatic cells.
      Title: A novel mechanism underlying alcohol dehydrogenase expression: hsa-miR-148a-3p promotes ADH4 expression via an AGO1-dependent manner in control and ethanol-exposed hepatic cells.
    4. Analysis of HCRTR2, GNB3, and ADH4 Gene Polymorphisms in a Southeastern European Caucasian Cluster Headache Population.
      Title: Analysis of HCRTR2, GNB3, and ADH4 Gene Polymorphisms in a Southeastern European Caucasian Cluster Headache Population.
    5. ADH4 expression is significantly downregulated in healthy palatal mucosa of smokers
      Title: Whole transcriptome analysis of smoker palatal mucosa identifies multiple downregulated innate immunity genes.
    6. Association between HCRTR2, ADH4,CLOCK gene polymorphisms and cluster headache was not significant in the present study.
      Title: Genetic association of HCRTR2, ADH4 and CLOCK genes with cluster headache: a Chinese population-based case-control study.
    7. this current study provides substantial evidence that genetic polymorphisms of rs3805322 in the ADH4 gene may be associated with an increased risk of developing ESCC in two Chinese Han populations.
      Title: Impact of alcohol dehydrogenase gene 4 polymorphisms on esophageal squamous cell carcinoma risk in a Chinese population.
    8. This study confirmed the genetic heterogeneity of cluster headache, suggesting that mutations in the ADH4 gene might be related to cluster headache in a subset of cases.
      Title: Molecular analysis of cluster headache.
    9. The serum expression of ADH4 protein correlates with the progression of esophageal cancer.
      Title: The alcohol dehydrogenase isoenzyme (ADH IV) as a candidate tumour marker of esophageal cancer.
    10. common ADH variants conferred risk for both schizophrenia in African-Americans and autism in European-Americans.
      Title: Association between common alcohol dehydrogenase gene (ADH) variants and schizophrenia and autism.
    Submit: New GeneRIF Correction See all GeneRIFs (31)

    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
    Extended genetic effects of ADH cluster genes on the risk of alcohol dependence: from GWAS to replication.
    EBI GWAS Catalog
    Genetic determinants influencing human serum metabolome among African Americans.
    EBI GWAS Catalog
    Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.
    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)

    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

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables NAD binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables NADPH:quinone reductase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables S-(hydroxymethyl)glutathione dehydrogenase [NAD(P)+] activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables alcohol dehydrogenase (NAD+) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables alcohol dehydrogenase (NAD+) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables aldose reductase (NADPH) activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables all-trans retinal binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables all-trans-retinol dehydrogenase (NAD+) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables benzaldehyde dehydrogenase (NAD+) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables retinol binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables zinc ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables zinc ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in alcohol catabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in alcohol metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cellular aldehyde metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in ethanol metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in fatty acid omega-oxidation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in formaldehyde catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in quinone metabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in retinoid metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in retinol metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    all-trans-retinol dehydrogenase [NAD(+)] ADH4
    Names
    alcohol dehydrogenase 2
    alcohol dehydrogenase class II pi chain
    aldehyde reductase
    epididymis secretory protein Li 4
    NP_000661.2
    NP_001293100.1
    NP_001293101.1

    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.

    mRNA and Protein(s)

    1. NM_000670.5 → NP_000661.2  all-trans-retinol dehydrogenase [NAD(+)] ADH4 isoform 2

      See identical proteins and their annotated locations for NP_000661.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and lacks an exon in the 5' coding region, which results in use of an alternate start codon compared to variant 1. It encodes isoform 2, which is shorter than and has a novel N-terminus compared to isoform 1.
      Source sequence(s)
      AC019131, AP002026
      Consensus CDS
      CCDS34032.1
      UniProtKB/Swiss-Prot
      A8K470, B4DIE7, C9J4A9, P08319, Q8TCD7
      UniProtKB/TrEMBL
      V9HVX7
      Related
      ENSP00000265512.7, ENST00000265512.12
      Conserved Domains (1) summary
      cd08299
      Location:3 → 380
      alcohol_DH_class_I_II_IV; class I, II, IV alcohol dehydrogenases

    2. NM_001306171.2 → NP_001293100.1  all-trans-retinol dehydrogenase [NAD(+)] ADH4 isoform 1

      See identical proteins and their annotated locations for NP_001293100.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). Variants 1 and 2 encode isoform 1.
      Source sequence(s)
      AC019131, AP002026
      Consensus CDS
      CCDS77942.1
      UniProtKB/TrEMBL
      V9HVX7
      Related
      ENSP00000424630.1, ENST00000508393.5
      Conserved Domains (1) summary
      cd08299
      Location:25 → 399
      alcohol_DH_class_I_II_IV; class I, II, IV alcohol dehydrogenases

    3. NM_001306172.2 → NP_001293101.1  all-trans-retinol dehydrogenase [NAD(+)] ADH4 isoform 1

      See identical proteins and their annotated locations for NP_001293101.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site in the 5' UTR compared to variant 1. Variants 1 and 2 encode isoform 1.
      Source sequence(s)
      AC019131, AP002026
      Consensus CDS
      CCDS77942.1
      UniProtKB/TrEMBL
      V9HVX7
      Related
      ENSP00000425416.1, ENST00000505590.5
      Conserved Domains (1) summary
      cd08299
      Location:25 → 399
      alcohol_DH_class_I_II_IV; class I, II, IV alcohol dehydrogenases

    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
      99123658..99144297 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060928.1 Alternate T2T-CHM13v2.0

      Range
      102438693..102459340 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P08319.5 GenPept UniProtKB/Swiss-Prot:P08319

    Gene LinkOut

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

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