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    MBD4 methyl-CpG binding domain 4, DNA glycosylase [ Homo sapiens (human) ]

    Gene ID: 8930, updated on 2-Nov-2024

    Summary

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    Official Symbol
    MBD4provided by HGNC
    Official Full Name
    methyl-CpG binding domain 4, DNA glycosylaseprovided by HGNC
    Primary source
    HGNC:HGNC:6919
    See related
    Ensembl:ENSG00000129071 MIM:603574; AllianceGenome:HGNC:6919
    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
    MED1; UVM1; TPDS2
    Summary
    The protein encoded by this gene is a member of a family of nuclear proteins related by the presence of a methyl-CpG binding domain (MBD). These proteins are capable of binding specifically to methylated DNA, and some members can also repress transcription from methylated gene promoters. This protein contains an MBD domain at the N-terminus that functions both in binding to methylated DNA and in protein interactions and a C-terminal mismatch-specific glycosylase domain that is involved in DNA repair. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]
    Expression
    Ubiquitous expression in lymph node (RPKM 27.7), spleen (RPKM 17.6) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See MBD4 in Genome Data Viewer
    Location:
    3q21.3
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (129430947..129439948, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (132175773..132184774, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (129149790..129158791, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ribosomal protein L32 pseudogene 3 Neighboring gene small nucleolar RNA, H/ACA box 7B Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:129129626-129130126 Neighboring gene EF-hand calcium binding domain 12 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:129137243-129137742 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20511 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14724 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20512 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20513 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20514 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20516 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20515 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20517 Neighboring gene Sharpr-MPRA regulatory region 8693 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:129168229-129168945 Neighboring gene intraflagellar transport 122 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:129200162-129201039 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:129208521-129208729 Neighboring gene Sharpr-MPRA regulatory region 10640 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:129213542-129214741 Neighboring gene MPRA-validated peak4826 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:129247433-129248158 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:129248159-129248884 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:129253999-129254668 Neighboring gene rhodopsin enhancer region Neighboring gene rhodopsin

    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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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Meta-analysis of the association between MBD4 Glu346Lys polymorphism and cancer risk.
      Title: Meta-analysis of the association between MBD4 Glu346Lys polymorphism and cancer risk.
    2. Familial uveal melanoma and other tumors in 25 families with monoallelic germline MBD4 variants.
      Title: Familial uveal melanoma and other tumors in 25 families with monoallelic germline MBD4 variants.
    3. MBD4 loss results in global reactivation of promoters and retroelements with low methylated CpG density.
      Title: MBD4 loss results in global reactivation of promoters and retroelements with low methylated CpG density.
    4. MBD4 deficiency is predictive of response to immune checkpoint inhibitors in metastatic uveal melanoma patients.
      Title: MBD4 deficiency is predictive of response to immune checkpoint inhibitors in metastatic uveal melanoma patients.
    5. Structural Insights into the Mechanism of Base Excision by MBD4.
      Title: Structural Insights into the Mechanism of Base Excision by MBD4.
    6. Germline MBD4 Mutations and Predisposition to Uveal Melanoma.
      Title: Germline MBD4 Mutations and Predisposition to Uveal Melanoma.
    7. Germline loss-of-function variants in MBD4 are rare in Finnish patients with uveal melanoma.
      Title: Germline loss-of-function variants in MBD4 are rare in Finnish patients with uveal melanoma.
    8. [Comparative Analysis of the Activity of the Polymorphic Variants of Human Uracil-DNA-Glycosylases SMUG1 and MBD4].
      Title: [Comparative Analysis of the Activity of the Polymorphic Variants of Human Uracil-DNA-Glycosylases SMUG1 and MBD4].
    9. MBD4 is sumoylated in vivo in a DNA damage-specific manner
      Title: Modification of the base excision repair enzyme MBD4 by the small ubiquitin-like molecule SUMO1.
    10. These findings suggest that RNF144A is epigenetically silenced in breast cancer cells by promoter hypermethylation and MBD4.
      Title: Epigenetic silencing of RNF144A expression in breast cancer cells through promoter hypermethylation and MBD4.
    Submit: New GeneRIF Correction See all GeneRIFs (46)

    Phenotypes

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    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Melanoma, uveal, susceptibility to, 1
    MedGen: C1847724 OMIM: 606660 GeneReviews: Not available
    		not available
    Tumor predisposition syndrome 2
    MedGen: C5774186 OMIM: 619975 GeneReviews: Not available
    		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)

    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 N-glycosylase activity TAS
    Traceable Author Statement
    more info
    		  
    enables DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables DNA endonuclease activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables pyrimidine-specific mismatch base pair DNA N-glycosylase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables satellite DNA binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA repair TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in depyrimidination TAS
    Traceable Author Statement
    more info
    		  
    involved_in response to estradiol IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in nuclear speck IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    methyl-CpG-binding domain protein 4
    Names
    3,N(4)-ethenocytosine glycosylase
    G/5-fluorouracil mismatch glycosylase with biphasic kinetics
    G/T mismatch glycosylase
    G/U mismatch glycosylase
    methyl-CpG binding domain protein 4
    methyl-CpG-binding endonuclease 1
    methyl-CpG-binding protein MBD4
    mismatch-specific DNA N-glycosylase
    putative methyl-CpG binding protein

    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_033106.1 RefSeqGene

      Range
      5232..14233
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001276270.2 → NP_001263199.1  methyl-CpG-binding domain protein 4 isoform 2

      See identical proteins and their annotated locations for NP_001263199.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.
      Source sequence(s)
      BC011752, BP370521, DB568237
      Consensus CDS
      CCDS63768.1
      UniProtKB/Swiss-Prot
      O95243
      Related
      ENSP00000394080.2, ENST00000429544.7
      Conserved Domains (2) summary
      smart00391
      Location:79 → 155
      MBD; Methyl-CpG binding domain
      cl23768
      Location:444 → 514
      ENDO3c; endonuclease III; includes endonuclease III (DNA-(apurinic or apyrimidinic site) lyase), alkylbase DNA glycosidases (Alka-family) and other DNA glycosidases

    2. NM_001276271.2 → NP_001263200.1  methyl-CpG-binding domain protein 4 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an exon and its transcription extends past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR compared to variant 1. It encodes isoform 3 which is shorter and has a distinct C-terminus, compared to isoform 1.
      Source sequence(s)
      AL449212
      Consensus CDS
      CCDS63766.1
      UniProtKB/Swiss-Prot
      O95243
      Related
      ENSP00000422327.1, ENST00000507208.1
      Conserved Domains (2) summary
      smart00391
      Location:79 → 155
      MBD; Methyl-CpG binding domain
      COG0177
      Location:453 → 518
      Nth; Endonuclease III [Replication, recombination and repair]

    3. NM_001276272.2 → NP_001263201.1  methyl-CpG-binding domain protein 4 isoform 4

      See identical proteins and their annotated locations for NP_001263201.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 4), compared to isoform 1.
      Source sequence(s)
      AF532602, DB568237
      Consensus CDS
      CCDS63767.1
      UniProtKB/Swiss-Prot
      O95243
      Related
      ENSP00000424873.1, ENST00000503197.5
      Conserved Domains (2) summary
      smart00391
      Location:79 → 155
      MBD; Methyl-CpG binding domain
      cl23768
      Location:450 → 520
      ENDO3c; endonuclease III; includes endonuclease III (DNA-(apurinic or apyrimidinic site) lyase), alkylbase DNA glycosidases (Alka-family) and other DNA glycosidases

    4. NM_001276273.2 → NP_001263202.1  methyl-CpG-binding domain protein 4 isoform 5

      See identical proteins and their annotated locations for NP_001263202.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate in-frame splice site and lacks an exon in the 5' coding region, compared to variant 1. The encoded isoform (5) is shorter, compared to isoform 1.
      Source sequence(s)
      AM180876, BP370521, CD678412, DB568237
      Consensus CDS
      CCDS63769.1
      UniProtKB/Swiss-Prot
      O95243
      Related
      ENSP00000376959.2, ENST00000393278.6
      Conserved Domains (1) summary
      cl23768
      Location:132 → 202
      ENDO3c; endonuclease III; includes endonuclease III (DNA-(apurinic or apyrimidinic site) lyase), alkylbase DNA glycosidases (Alka-family) and other DNA glycosidases

    5. NM_003925.3 → NP_003916.1  methyl-CpG-binding domain protein 4 isoform 1

      See identical proteins and their annotated locations for NP_003916.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AF072250, BY997577, DB568237
      Consensus CDS
      CCDS3058.1
      UniProtKB/Swiss-Prot
      B4DZN2, D3DNC3, D3DNC4, E9PEE4, O95243, Q2MD36, Q7Z4T3, Q96F09
      Related
      ENSP00000249910.1, ENST00000249910.5
      Conserved Domains (2) summary
      smart00391
      Location:79 → 155
      MBD; Methyl-CpG binding domain
      cl23768
      Location:450 → 520
      ENDO3c; endonuclease III; includes endonuclease III (DNA-(apurinic or apyrimidinic site) lyase), alkylbase DNA glycosidases (Alka-family) and other DNA glycosidases

    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_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      129430947..129439948 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047449153.1 → XP_047305109.1  methyl-CpG-binding domain protein 4 isoform X2

    2. XM_024453810.2 → XP_024309578.1  methyl-CpG-binding domain protein 4 isoform X1

      Conserved Domains (2) summary
      smart00391
      Location:79 → 155
      MBD; Methyl-CpG binding domain
      cl27658
      Location:447 → 512
      HHH; Helix-hairpin-helix motif

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      132175773..132184774 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054348285.1 → XP_054204260.1  methyl-CpG-binding domain protein 4 isoform X2

    2. XM_054348284.1 → XP_054204259.1  methyl-CpG-binding domain protein 4 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O95243.1 GenPept UniProtKB/Swiss-Prot:O95243

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