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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
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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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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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