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    HDAC8 histone deacetylase 8 [ Homo sapiens (human) ]

    Gene ID: 55869, updated on 10-Dec-2024

    Summary

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    Official Symbol
    HDAC8provided by HGNC
    Official Full Name
    histone deacetylase 8provided by HGNC
    Primary source
    HGNC:HGNC:13315
    See related
    Ensembl:ENSG00000147099 MIM:300269; AllianceGenome:HGNC:13315
    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
    HD8; WTS; RPD3; CDA07; CDLS5; KDAC8; MRXS6; HDACL1
    Summary
    Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class I of the histone deacetylase family. It catalyzes the deacetylation of lysine residues in the histone N-terminal tails and represses transcription in large multiprotein complexes with transcriptional co-repressors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
    Expression
    Ubiquitous expression in adrenal (RPKM 3.9), thyroid (RPKM 3.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HDAC8 in Genome Data Viewer
    Location:
    Xq13.1
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (72329516..72572843, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (70762405..71005758, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (71549366..71792693, complement)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29757 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29758 Neighboring gene uncharacterized LOC105373250 Neighboring gene Sharpr-MPRA regulatory region 2135 Neighboring gene NANOG hESC enhancer GRCh37_chrX:71528736-71529237 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:71532082-71532582 Neighboring gene ribosomal protein S4 X-linked Neighboring gene Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29761 Neighboring gene RNA, U2 small nuclear 68, pseudogene Neighboring gene MED14-independent group 3 enhancer GRCh37_chrX:71773892-71775091 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29762 Neighboring gene phosphorylase kinase regulatory subunit alpha 1 Neighboring gene MATR3 pseudogene 1 Neighboring gene PHKA1 antisense RNA 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. Binding of the Microbial Cyclic Tetrapeptide Trapoxin A to the Class I Histone Deacetylase HDAC8. Porter NJ, et al. ACS Chem Biol, 2017 Sep 15. PMID 28846375, Free PMC Article
    2. Histone deacetylase 8 is required for centrosome cohesion and influenza A virus entry. Yamauchi Y, et al. PLoS Pathog, 2011 Oct. PMID 22046129, Free PMC Article
    3. Structural and Functional Influence of the Glycine-Rich Loop G(302)GGGY on the Catalytic Tyrosine of Histone Deacetylase 8. Porter NJ, et al. Biochemistry, 2016 Dec 6. PMID 27933794, Free PMC Article
    4. Histone deacetylase 8 as a novel therapeutic target in oral squamous cell carcinoma. Ahn MY, et al. Oncol Rep, 2017 Jan. PMID 28004115
    5. cAMP signaling increases histone deacetylase 8 expression via the Epac2-Rap1A-Akt pathway in H1299 lung cancer cells. Park JY, et al. Exp Mol Med, 2017 Feb 24. PMID 28232663, Free PMC Article

    See all (146) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Reversible acetylation of HDAC8 regulates cell cycle.
      Title: Reversible acetylation of HDAC8 regulates cell cycle.
    2. hRpn13 shapes the proteome and transcriptome through epigenetic factors HDAC8, PADI4, and transcription factor NF-kappaB p50.
      Title: hRpn13 shapes the proteome and transcriptome through epigenetic factors HDAC8, PADI4, and transcription factor NF-κB p50.
    3. HDAC8-mediated inhibition of EP300 drives a transcriptional state that increases melanoma brain metastasis.
      Title: HDAC8-mediated inhibition of EP300 drives a transcriptional state that increases melanoma brain metastasis.
    4. Activation of HDAC8 Can Suppress the Proliferation of Osteosarcoma Cells via TP53 and STAT3/ERK Signaling Pathways.
      Title: Activation of HDAC8 Can Suppress the Proliferation of Osteosarcoma Cells via TP53 and STAT3/ERK Signaling Pathways.
    5. HDAC8 as an emerging target in drug discovery with special emphasis on medicinal chemistry.
      Title: HDAC8 as an emerging target in drug discovery with special emphasis on medicinal chemistry.
    6. Histone deacetylase 8 inhibition prevents the progression of peritoneal fibrosis by counteracting the epithelial-mesenchymal transition and blockade of M2 macrophage polarization.
      Title: Histone deacetylase 8 inhibition prevents the progression of peritoneal fibrosis by counteracting the epithelial-mesenchymal transition and blockade of M2 macrophage polarization.
    7. Chemically Diverse S. mansoni HDAC8 Inhibitors Reduce Viability in Worm Larval and Adult Stages.
      Title: Chemically Diverse S. mansoni HDAC8 Inhibitors Reduce Viability in Worm Larval and Adult Stages.
    8. PHF5A Contributes to the Maintenance of the Cancer Stem-like Phenotype in Non-Small Cell Lung Cancer by Regulating Histone Deacetylase 8.
      Title: PHF5A Contributes to the Maintenance of the Cancer Stem-like Phenotype in Non-Small Cell Lung Cancer by Regulating Histone Deacetylase 8.
    9. Structural analysis of histone deacetylase 8 mutants associated with Cornelia de Lange Syndrome spectrum disorders.
      Title: Structural analysis of histone deacetylase 8 mutants associated with Cornelia de Lange Syndrome spectrum disorders.
    10. HDAC8 Activates AKT through Upregulating PLCB1 and Suppressing DESC1 Expression in MEK1/2 Inhibition-Resistant Cells.
      Title: HDAC8 Activates AKT through Upregulating PLCB1 and Suppressing DESC1 Expression in MEK1/2 Inhibition-Resistant Cells.
    Submit: New GeneRIF Correction See all GeneRIFs (110)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Cornelia de Lange syndrome 5
    MedGen: C3550903 OMIM: 300882 GeneReviews: Cornelia de Lange Syndrome
    		Compare labs
    De Lange syndrome
    MedGen: C0270972 GeneReviews: Cornelia de Lange Syndrome
    		Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated 2018-03-28)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated 2018-03-28)

    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)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Vpr vpr HIV-1 Vpr depletes HDAC1, 2, 3 and 8 to overcome HIV-1 proviral latency in 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 DNA-binding transcription factor binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables Hsp70 protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables Hsp90 protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables histone H3K14 deacetylase activity, hydrolytic mechanism IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3K4 deacetylase activity, hydrolytic mechanism IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3K9 deacetylase activity, hydrolytic mechanism IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H4K12 deacetylase activity, hydrolytic mechanism IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H4K16 deacetylase activity, hydrolytic mechanism IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H4K5 deacetylase activity, hydrolytic mechanism IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H4K8 deacetylase activity, hydrolytic mechanism IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone deacetylase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables histone deacetylase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables histone deacetylase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables histone decrotonylase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein lysine deacetylase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables tubulin deacetylase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in chromatin organization TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in heterochromatin formation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in mitotic sister chromatid cohesion IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in negative regulation of transcription by RNA polymerase II TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of protein stability IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of telomere maintenance IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytoplasm TAS
    Traceable Author Statement
    more info
    		 PubMed 
    part_of histone deacetylase complex TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in nuclear chromosome TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    histone deacetylase 8
    Names
    histone deacetylase-like 1
    protein deacetylase HDAC8
    protein decrotonylase HDAC8
    NP_001159890.1
    NP_001159891.1
    NP_001159892.1
    NP_001159894.1
    NP_001159920.1
    NP_001397654.1
    NP_001397656.1
    NP_001397657.1
    NP_001397658.1
    NP_001397659.1
    NP_060956.1
    XP_016885129.2
    XP_016885132.2
    XP_016885133.2
    XP_016885134.2
    XP_047298208.1
    XP_047298211.1
    XP_047298212.1
    XP_047298213.1
    XP_054183365.1
    XP_054183366.1
    XP_054183367.1
    XP_054183368.1
    XP_054183369.1
    XP_054183370.1
    XP_054183371.1
    XP_054183372.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_015851.1 RefSeqGene

      Range
      5261..248588
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001166418.2 → NP_001159890.1  histone deacetylase 8 isoform 2

      See identical proteins and their annotated locations for NP_001159890.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks two alternate exons in the 5' coding region, compared to variant 1, resulting in a protein (isoform 2) that maintains the reading frame but is shorter, compared to isoform 1.
      Source sequence(s)
      AK296641, BC050433
      Consensus CDS
      CCDS55449.1
      UniProtKB/TrEMBL
      A0A3B3ISE4
      Related
      ENSP00000362691.4, ENST00000373589.9
      Conserved Domains (1) summary
      cl17011
      Location:16 → 286
      Arginase_HDAC; Arginase-like and histone-like hydrolases

    2. NM_001166419.2 → NP_001159891.1  histone deacetylase 8 isoform 3

      See identical proteins and their annotated locations for NP_001159891.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks several alternate 3' exons and uses an alternate 3' terminal exon, compared to variant 1. The encoded isoform (3) has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AK074326
      Consensus CDS
      CCDS55451.1
      UniProtKB/TrEMBL
      A0A3B3IRZ8
      Related
      ENSP00000414486.2, ENST00000439122.7
      Conserved Domains (1) summary
      cl17011
      Location:16 → 246
      Arginase_HDAC; Arginase-like and histone-like hydrolases

    3. NM_001166420.2 → NP_001159892.1  histone deacetylase 8 isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks a large portion of the 3' coding region and has a distinct 3' UTR, compared to variant 1. The encoded isoform (5) has a shorter C-terminus, compared to isoform 1.
      Source sequence(s)
      AI651236, BF514915, BQ189619
      Consensus CDS
      CCDS55450.1
      UniProtKB/TrEMBL
      A0A3B3IS93
      Related
      ENSP00000362655.1, ENST00000373554.6
      Conserved Domains (1) summary
      cl17011
      Location:16 → 146
      Arginase_HDAC; Arginase-like and histone-like hydrolases

    4. NM_001166422.2 → NP_001159894.1  histone deacetylase 8 isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) lacks multiple alternate 3' exons and uses an alternate 3' terminal exon, compared to variant 1. The encoded isoform (5) has a shorter and distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AI651236, AI916593, BP229332
      Consensus CDS
      CCDS55452.1
      UniProtKB/TrEMBL
      A0A3B3IS93
      Related
      ENSP00000362657.3, ENST00000373556.8
      Conserved Domains (1) summary
      cl17011
      Location:16 → 147
      Arginase_HDAC; Arginase-like and histone-like hydrolases

    5. NM_001166448.2 → NP_001159920.1  histone deacetylase 8 isoform 6

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) lacks multiple alternate coding exons and uses an alternate 3' terminal exon, compared to variant 1. The encoded isoform (3) maintains the reading frame, but is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AK074326, BP229332, BQ632790
      Consensus CDS
      CCDS55448.1
      UniProtKB/Swiss-Prot
      Q9BY41
      Related
      ENSP00000362660.4, ENST00000373559.8
      Conserved Domains (1) summary
      cl17011
      Location:16 → 129
      Arginase_HDAC; Arginase-like and histone-like hydrolases

    6. NM_001410725.1 → NP_001397654.1  histone deacetylase 8 isoform 7

      Status: REVIEWED

      Source sequence(s)
      AL133500, BX295542
      Consensus CDS
      CCDS94633.1
      UniProtKB/TrEMBL
      A0A3B3IS68, A0A3B3ISJ4
      Related
      ENSP00000497188.1, ENST00000647886.1

    7. NM_001410727.1 → NP_001397656.1  histone deacetylase 8 isoform 8

      Status: REVIEWED

      Source sequence(s)
      AL133500, BX295542
      Consensus CDS
      CCDS94631.1
      UniProtKB/TrEMBL
      A0A3B3ITZ3, A6NFW1
      Related
      ENSP00000362685.2, ENST00000373583.6

    8. NM_001410728.1 → NP_001397657.1  histone deacetylase 8 isoform 9

      Status: REVIEWED

      Source sequence(s)
      AL133500, BX295542
      Consensus CDS
      CCDS94630.1
      UniProtKB/TrEMBL
      A0A3B3IT30
      Related
      ENSP00000497568.1, ENST00000647654.1

    9. NM_001410729.1 → NP_001397658.1  histone deacetylase 8 isoform 10

      Status: REVIEWED

      Source sequence(s)
      AL133500, BX295542
      Consensus CDS
      CCDS94634.1
      UniProtKB/TrEMBL
      A0A3B3ISS7, A0A3B3IT95
      Related
      ENSP00000497764.1, ENST00000648834.1

    10. NM_001410730.1 → NP_001397659.1  histone deacetylase 8 isoform 11

      Status: REVIEWED

      Source sequence(s)
      AL133500, BX295542
      Consensus CDS
      CCDS94632.1
      UniProtKB/TrEMBL
      A0A3B3IRZ8, A0A3B3IU01
      Related
      ENSP00000498144.1, ENST00000650126.1

    11. NM_018486.3 → NP_060956.1  histone deacetylase 8 isoform 1

      See identical proteins and their annotated locations for NP_060956.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AJ277724, BC050433, BP229332
      Consensus CDS
      CCDS14420.1
      UniProtKB/Swiss-Prot
      A6ND12, A6ND61, A6NET3, A6NJR3, A8MQ62, B4DKN0, B4DV22, Q86VC8, Q9BY41, Q9NP76, Q9NYH4
      UniProtKB/TrEMBL
      A0A3B3ITZ3
      Related
      ENSP00000362674.3, ENST00000373573.9
      Conserved Domains (1) summary
      cd10000
      Location:16 → 377
      HDAC8; Histone deacetylase 8 (HDAC8)

    RNA

    1. NR_051952.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) lacks an internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK298767, BC050433, DC352390
      Related
      ENST00000650471.1

    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_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      72329516..72572843 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047442255.1 → XP_047298211.1  histone deacetylase 8 isoform X6

      UniProtKB/TrEMBL
      A0A3B3ISE4

    2. XM_017029644.3 → XP_016885133.2  histone deacetylase 8 isoform X4

    3. XM_017029645.3 → XP_016885134.2  histone deacetylase 8 isoform X5

      UniProtKB/TrEMBL
      A0A3B3IRJ3
      Related
      ENSP00000496818.1, ENST00000648139.1

    4. XM_017029643.3 → XP_016885132.2  histone deacetylase 8 isoform X3

      UniProtKB/TrEMBL
      A0A3B3IRJ3

    5. XM_017029640.3 → XP_016885129.2  histone deacetylase 8 isoform X1

      UniProtKB/TrEMBL
      A0A3B3ISJ4
      Conserved Domains (1) summary
      cd10000
      Location:16 → 345
      HDAC8; Histone deacetylase 8 (HDAC8)

    6. XM_047442256.1 → XP_047298212.1  histone deacetylase 8 isoform X7

    7. XM_047442257.1 → XP_047298213.1  histone deacetylase 8 isoform X8

      UniProtKB/TrEMBL
      B4DQE7, E7ETC8

    8. XM_047442252.1 → XP_047298208.1  histone deacetylase 8 isoform X2

      UniProtKB/TrEMBL
      A0A3B3IT84
      Related
      ENSP00000396424.2, ENST00000415409.6

    RNA

    1. XR_938402.4 RNA Sequence

      Related
      ENST00000647594.1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      70762405..71005758 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054327395.1 → XP_054183370.1  histone deacetylase 8 isoform X6

      UniProtKB/TrEMBL
      A0A3B3ISE4

    2. XM_054327393.1 → XP_054183368.1  histone deacetylase 8 isoform X4

    3. XM_054327394.1 → XP_054183369.1  histone deacetylase 8 isoform X5

      UniProtKB/TrEMBL
      A0A3B3IRJ3

    4. XM_054327392.1 → XP_054183367.1  histone deacetylase 8 isoform X3

      UniProtKB/TrEMBL
      A0A3B3IRJ3

    5. XM_054327390.1 → XP_054183365.1  histone deacetylase 8 isoform X1

      UniProtKB/TrEMBL
      A0A3B3ISJ4

    6. XM_054327396.1 → XP_054183371.1  histone deacetylase 8 isoform X7

    7. XM_054327397.1 → XP_054183372.1  histone deacetylase 8 isoform X8

      UniProtKB/TrEMBL
      B4DQE7, E7ETC8

    8. XM_054327391.1 → XP_054183366.1  histone deacetylase 8 isoform X2

      UniProtKB/TrEMBL
      A0A3B3IT84

    RNA

    1. XR_008485495.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BY41.2 GenPept UniProtKB/Swiss-Prot:Q9BY41

    Gene LinkOut

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

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