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    NHLRC1 NHL repeat containing E3 ubiquitin protein ligase 1 [ Homo sapiens (human) ]

    Gene ID: 378884, updated on 10-Dec-2024

    Summary

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    Official Symbol
    NHLRC1provided by HGNC
    Official Full Name
    NHL repeat containing E3 ubiquitin protein ligase 1provided by HGNC
    Primary source
    HGNC:HGNC:21576
    See related
    Ensembl:ENSG00000187566 MIM:608072; AllianceGenome:HGNC:21576
    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
    EPM2A; EPM2B; MALIN; MELF2; bA204B7.2
    Summary
    The protein encoded by this gene is a single subunit E3 ubiquitin ligase. Laforin is polyubiquitinated by the encoded protein. Defects in this intronless gene lead to an accumulation of laforin and onset of Lafora disease, also known as progressive myoclonic epilepsy type 2 (EPM2).[provided by RefSeq, Mar 2010]
    Orthologs
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    Genomic context

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    See NHLRC1 in Genome Data Viewer
    Location:
    6p22.3
    Exon count:
    1
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (18120440..18122677, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (17992610..17994847, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (18120671..18122908, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene kinesin family member 13A Neighboring gene uncharacterized LOC105374953 Neighboring gene Sharpr-MPRA regulatory region 4275 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:17934402-17934586 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:17940169-17940668 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:17976631-17977191 Neighboring gene ribosomal protein S12 pseudogene 12 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16967 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16968 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24116 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:18022491-18023444 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:18089369-18090086 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr6:18146951-18148150 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16969 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24117 Neighboring gene MPRA-validated peak5710 silencer Neighboring gene thiopurine S-methyltransferase Neighboring gene lysine demethylase 1B Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24118 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16970 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24119

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Lafora disease due to EPM2B mutations: a clinical and genetic study. Gómez-Abad C, et al. Neurology, 2005 Mar 22. PMID 15781812
    2. Rapidly progressive phenotype of Lafora disease associated with a novel NHLRC1 mutation. Brackmann FA, et al. Pediatr Neurol, 2011 Jun. PMID 21555062
    3. Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease. Traoré M, et al. Neurogenetics, 2009 Oct. PMID 19322595, Free PMC Article
    4. Lafora progressive myoclonus epilepsy: disease course homogeneity in a genetic isolate. Turnbull J, et al. J Child Neurol, 2008 Feb. PMID 18263761
    5. Novel NHLRC1 mutations and genotype-phenotype correlations in patients with Lafora's progressive myoclonic epilepsy. Singh S, et al. J Med Genet, 2006 Sep. PMID 16950819, Free PMC Article

    See all (53) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Identification of NHLRC1 as a Novel AKT Activator from a Lung Cancer Epigenome-Wide Association Study (EWAS).
      Title: Identification of NHLRC1 as a Novel AKT Activator from a Lung Cancer Epigenome-Wide Association Study (EWAS).
    2. Compound heterozygosity for novel variations of the NHLRC1 Gene in a family with Lafora disease.
      Title: Compound heterozygosity for novel variations of the NHLRC1 Gene in a family with Lafora disease.
    3. The rare rs769301934 variant in NHLRC1 is a common cause of Lafora disease in Turkey.
      Title: The rare rs769301934 variant in NHLRC1 is a common cause of Lafora disease in Turkey.
    4. Laforin/malin complex interacts physically and co-localizes intracellularly with core components of the PI3KC3 complex (Beclin1, Vps34 and Vps15), and that this interaction is specific and results in the polyubiquitination of these proteins.
      Title: Regulation of the autophagic PI3KC3 complex by laforin/malin E3-ubiquitin ligase, two proteins involved in Lafora disease.
    5. Malin promotes its own degradation via auto-ubiquitination.Malin preferentially degrades the phosphatase-inactive laforin monomer.
      Title: Interdependence of laforin and malin proteins for their stability and functions could underlie the molecular basis of locus heterogeneity in Lafora disease.
    6. laforin/malin complex is able to interact with and ubiquitinate both PKM1 and PKM2
      Title: The laforin/malin E3-ubiquitin ligase complex ubiquitinates pyruvate kinase M1/M2.
    7. Lafora disease proteins laforin and malin negatively regulate the HIPK2-p53 cell death pathway.
      Title: Lafora disease proteins laforin and malin negatively regulate the HIPK2-p53 cell death pathway.
    8. This study demonistrated that NHLRC1 mutations were detected in some case of Mild Lafora disease patients.
      Title: Mild Lafora disease: clinical, neurophysiologic, and genetic findings.
    9. Without functional laforin-malin complex assembled on polyglucosan bodies, polyglucosan is not degraded.
      Title: Laforin-malin complex degrades polyglucosan bodies in concert with glycogen debranching enzyme and brain isoform glycogen phosphorylase.
    10. Malin regulates the recruitment of mRNA-decapping enzyme 1A (Dcp1a) to processing bodies.
      Title: Lafora disease E3 ubiquitin ligase malin is recruited to the processing bodies and regulates the microRNA-mediated gene silencing process via the decapping enzyme Dcp1a.
    Submit: New GeneRIF Correction See all GeneRIFs (37)

    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

    Associated conditions

    Description Tests
    Myoclonic epilepsy of Lafora 2
    MedGen: C1850764 OMIM: 620681 GeneReviews: Progressive Myoclonus Epilepsy, Lafora Type
    		Compare labs

    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

    • MGC119262, MGC119264, MGC119265

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin-protein transferase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables ubiquitin-protein transferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquitin-protein transferase activity TAS
    Traceable Author Statement
    more info
    		  
    Process Evidence Code Pubs
    involved_in autophagy IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in glycogen biosynthetic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in positive regulation of protein ubiquitination IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein polyubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein polyubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in regulation of protein localization to plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to endoplasmic reticulum stress IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in endoplasmic reticulum IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    E3 ubiquitin-protein ligase NHLRC1
    Names
    NHL repeat containing 1
    NHL repeat-containing protein 1
    RING-type E3 ubiquitin transferase NHLRC1
    NP_940988.2

    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_016750.1 RefSeqGene

      Range
      4944..7181
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_198586.3 → NP_940988.2  E3 ubiquitin-protein ligase NHLRC1

      See identical proteins and their annotated locations for NP_940988.2

      Status: REVIEWED

      Source sequence(s)
      AL589723, BK001510
      Consensus CDS
      CCDS4542.1
      UniProtKB/Swiss-Prot
      Q3SYB1, Q5VUK7, Q6IMH1, Q6VVB1
      Related
      ENSP00000345464.3, ENST00000340650.6
      Conserved Domains (3) summary
      cd14961
      Location:118 → 391
      NHL_TRIM32_like; NHL repeat domain of the tripartite motif-containing protein 32 (TRIM32) and related proteins
      cd16516
      Location:25 → 72
      RING-HC_malin; RING finger, HC subclass, found in malin and similar proteins
      cl28192
      Location:53 → 133
      HemN; Coproporphyrinogen III oxidase or related Fe-S oxidoreductase [Coenzyme transport and metabolism]

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      18120440..18122677 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      17992610..17994847 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q6VVB1.2 GenPept UniProtKB/Swiss-Prot:Q6VVB1

    Gene LinkOut

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