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    LEMD2 LEM domain nuclear envelope protein 2 [ Homo sapiens (human) ]

    Gene ID: 221496, updated on 2-Nov-2024

    Summary

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    Official Symbol
    LEMD2provided by HGNC
    Official Full Name
    LEM domain nuclear envelope protein 2provided by HGNC
    Primary source
    HGNC:HGNC:21244
    See related
    Ensembl:ENSG00000161904 MIM:616312; AllianceGenome:HGNC:21244
    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
    LEM2; NET25; MARUPS; CTRCT42; dJ482C21.1
    Summary
    This gene encodes a LEM domain-containing transmembrane protein of the inner nuclear membrane. The protein is involved in nuclear structure organization and plays a role in cell signaling and differentiation. Mutations in this gene result in Cataract 46, juvenile-onset. Multiple transcript variants have been found for this gene. [provided by RefSeq, Feb 2017]
    Expression
    Ubiquitous expression in testis (RPKM 4.6), spleen (RPKM 4.4) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See LEMD2 in Genome Data Viewer
    Location:
    6p21.31
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (33771213..33789130, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (33592393..33610310, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (33738990..33756907, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene ubiquinol-cytochrome c reductase complex assembly factor 2 Neighboring gene uncharacterized LOC124901304 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:33678073-33678970 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24368 Neighboring gene Sharpr-MPRA regulatory region 11056 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr6:33692274-33693024 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33695430-33696209 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33696210-33696988 Neighboring gene inositol hexakisphosphate kinase 3 Neighboring gene ReSE screen-validated silencer GRCh37_chr6:33703405-33703659 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33710674-33711363 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33711622-33712515 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33712516-33713408 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:33713409-33714302 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33718585-33719144 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:33719703-33720261 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33728947-33729550 Neighboring gene Sharpr-MPRA regulatory region 8162 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17054 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17055 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33740622-33741320 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:33747376-33748316 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:33748317-33749256 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:33750197-33751135 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:33755871-33756420 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17057 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24369 Neighboring gene uncharacterized LOC105375024 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33758333-33758936 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33775949-33776449 Neighboring gene motilin Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr6:33778261-33779022 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr6:33779784-33780545 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:33780546-33781306 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr6:33786695-33787196 Neighboring gene uncharacterized LOC105375025

    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. The Role of the LEMD2 p.L13R Mutation in Dilated Cardiomyopathy. Vargas JD. Circ Res, 2023 Jan 20. PMID 36656966
    2. The Discovery of a LEMD2-Associated Nuclear Envelopathy with Early Progeroid Appearance Suggests Advanced Applications for AI-Driven Facial Phenotyping. Marbach F, et al. Am J Hum Genet, 2019 Apr 4. PMID 30905398, Free PMC Article
    3. Comparative Interactome Analysis of Emerin, MAN1 and LEM2 Reveals a Unique Role for LEM2 in Nucleotide Excision Repair. Moser B, et al. Cells, 2020 Feb 18. PMID 32085595, Free PMC Article
    4. LEM2 phase separation promotes ESCRT-mediated nuclear envelope reformation. von Appen A, et al. Nature, 2020 Jun. PMID 32494070, Free PMC Article
    5. Loss of function of the nuclear envelope protein LEMD2 causes DNA damage-dependent cardiomyopathy. Caravia XM, et al. J Clin Invest, 2022 Nov 15. PMID 36377660, Free PMC Article

    See all (61) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The Role of the LEMD2 p.L13R Mutation in Dilated Cardiomyopathy.
      Title: The Role of the LEMD2 p.L13R Mutation in Dilated Cardiomyopathy.
    2. Loss of function of the nuclear envelope protein LEMD2 causes DNA damage-dependent cardiomyopathy.
      Title: Loss of function of the nuclear envelope protein LEMD2 causes DNA damage-dependent cardiomyopathy.
    3. SATB2-LEMD2 interaction links nuclear shape plasticity to regulation of cognition-related genes.
      Title: SATB2-LEMD2 interaction links nuclear shape plasticity to regulation of cognition-related genes.
    4. Regulated lipid synthesis and LEM2/CHMP7 jointly control nuclear envelope closure.
      Title: Regulated lipid synthesis and LEM2/CHMP7 jointly control nuclear envelope closure.
    5. Comparative Interactome Analysis of Emerin, MAN1 and LEM2 Reveals a Unique Role for LEM2 in Nucleotide Excision Repair.
      Title: Comparative Interactome Analysis of Emerin, MAN1 and LEM2 Reveals a Unique Role for LEM2 in Nucleotide Excision Repair.
    6. LEM2 phase separation promotes ESCRT-mediated nuclear envelope reformation
      Title: LEM2 phase separation promotes ESCRT-mediated nuclear envelope reformation.
    7. LEMD2 is required for recruitment of the ESCRT-III membrane repair machinery to ruptures; however, neither LEMD2 nor ESCRT-III is required to repair ruptures. These results reveal a new role for BAF in the response to and repair of nuclear ruptures.
      Title: Repair of nuclear ruptures requires barrier-to-autointegration factor.
    8. a recurrent de novo mutation in LEMD2 causes a nuclear envelopathy whose prognosis in adolescence is relatively good in comparison to that of classical Hutchinson-Gilford progeria syndrome
      Title: The Discovery of a LEMD2-Associated Nuclear Envelopathy with Early Progeroid Appearance Suggests Advanced Applications for AI-Driven Facial Phenotyping.
    9. We conclude that Lem2p/LEM2 is a conserved nuclear site-specific adaptor that recruits Cmp7p/CHMP7 and downstream ESCRT factors to the nuclear envelope.
      Title: LEM2 recruits CHMP7 for ESCRT-mediated nuclear envelope closure in fission yeast and human cells.
    10. Observational study of gene-disease association. (HuGE Navigator)
      Title: High-density SNP screening of the major histocompatibility complex in systemic lupus erythematosus demonstrates strong evidence for independent susceptibility regions.
    Submit: New GeneRIF Correction

    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
    Cataract 46 juvenile-onset
    MedGen: C0220721 OMIM: 212500 GeneReviews: Not available
    		Compare labs
    Marbach-Rustad progeroid syndrome
    MedGen: C5543388 OMIM: 619322 GeneReviews: Not available
    		Compare labs

    EBI GWAS Catalog

    Description
    Common genetic variants associate with serum phosphorus concentration.
    EBI GWAS Catalog
    Genome-wide association analysis of age-at-onset in Alzheimer's disease.
    EBI GWAS Catalog
    Genome-wide association study of Crohn's disease in Koreans revealed three new susceptibility loci and common attributes of genetic susceptibility across ethnic populations.
    EBI GWAS Catalog
    Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
    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 protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in heart formation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of MAPK cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in neurogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in nuclear envelope organization IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in nuclear membrane organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein localization to chromatin IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within skeletal muscle cell differentiation IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    colocalizes_with endoplasmic reticulum IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in membrane HDA PubMed 
    located_in membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    colocalizes_with nuclear envelope IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nuclear envelope TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nuclear inner membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nuclear inner membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nuclear inner membrane TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in nuclear membrane IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nuclear periphery IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in spindle IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    LEM domain-containing protein 2
    Names
    LEM domain containing 2
    hLEM2
    lamina-associated polypeptide-emerin-MAN1 domain containing 2

    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_053042.1 RefSeqGene

      Range
      10145..28062
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001143944.1 → NP_001137416.1  LEM domain-containing protein 2 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.
      Source sequence(s)
      AK024858, BC039864, BM978238, DC340017
      Consensus CDS
      CCDS47411.1
      UniProtKB/Swiss-Prot
      Q8NC56
      Related
      ENSP00000421704.1, ENST00000508327.5
      Conserved Domains (1) summary
      pfam09402
      Location:56 → 191
      MSC; Man1-Src1p-C-terminal domain

    2. NM_001348709.2 → NP_001335638.1  LEM domain-containing protein 2 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AL158049
      Consensus CDS
      CCDS47411.1
      UniProtKB/Swiss-Prot
      Q8NC56
      Conserved Domains (1) summary
      pfam09402
      Location:56 → 191
      MSC; Man1-Src1p-C-terminal domain

    3. NM_001348710.2 → NP_001335639.1  LEM domain-containing protein 2 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AL158049
      UniProtKB/TrEMBL
      A0A220T1R7
      Conserved Domains (2) summary
      cd12941
      Location:4 → 41
      LEM_LEMD2; LEM (Lap2/Emerin/Man1) domain found in LEM domain-containing protein 2 (LEM2)
      pfam09402
      Location:145 → 360
      MSC; Man1-Src1p-C-terminal domain

    4. NM_181336.4 → NP_851853.1  LEM domain-containing protein 2 isoform 1

      See identical proteins and their annotated locations for NP_851853.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longest isoform (1).
      Source sequence(s)
      AK024858, AL158049, BC039864, BM978238
      Consensus CDS
      CCDS4785.1
      UniProtKB/Swiss-Prot
      B4DVH5, E7EVT2, Q5T972, Q5T974, Q8NC56
      Related
      ENSP00000293760.5, ENST00000293760.10
      Conserved Domains (2) summary
      pfam09402
      Location:278 → 493
      MSC; Man1-Src1p-C-terminal domain
      cl02649
      Location:4 → 41
      LEM; LEM (Lap2/Emerin/Man1) domain found in emerin, lamina-associated polypeptide 2 (LAP2), inner nuclear membrane protein Man1 and similar 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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      33771213..33789130 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047418349.1 → XP_047274305.1  LEM domain-containing protein 2 isoform X2

    2. XM_017010437.2 → XP_016865926.2  LEM domain-containing protein 2 isoform X1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      33592393..33610310 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054354596.1 → XP_054210571.1  LEM domain-containing protein 2 isoform X2

    2. XM_054354595.1 → XP_054210570.1  LEM domain-containing protein 2 isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8NC56.1 GenPept UniProtKB/Swiss-Prot:Q8NC56

    Gene LinkOut

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

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