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LEMD3 LEM domain containing 3 [ Homo sapiens (human) ]

Gene ID: 23592, updated on 2-May-2024

Summary

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Official Symbol
LEMD3provided by HGNC
Official Full Name
LEM domain containing 3provided by HGNC
Primary source
HGNC:HGNC:28887
See related
Ensembl:ENSG00000174106 MIM:607844; AllianceGenome:HGNC:28887
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
MAN1
Summary
This locus encodes a LEM domain-containing protein. The encoded protein functions to antagonize transforming growth factor-beta signaling at the inner nuclear membrane. Two transcript variants encoding different isoforms have been found for this gene. Mutations in this gene have been associated with osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis.[provided by RefSeq, Nov 2009]
Expression
Ubiquitous expression in testis (RPKM 11.8), bone marrow (RPKM 7.8) and 25 other tissues See more
Orthologs
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Genomic context

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See LEMD3 in Genome Data Viewer
Location:
12q14.3
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (65169583..65248355)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (65148505..65227374)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (65563363..65642135)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6605 Neighboring gene apolipoprotein O pseudogene 3 Neighboring gene uncharacterized LOC124902953 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6606 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:65563126-65563698 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4630 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:65564244-65564447 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6608 Neighboring gene Sharpr-MPRA regulatory region 14888 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4631 Neighboring gene MPRA-validated peak1765 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:65655701-65656202 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:65656203-65656702 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4632 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4633 Neighboring gene methionine sulfoxide reductase B3 Neighboring gene uncharacterized LOC124902954 Neighboring gene keratin 18 pseudogene 60

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. LEM domain-containing protein 3 antagonizes TGFβ-SMAD2/3 signaling in a stiffness-dependent manner in both the nucleus and cytosol. Chambers DM, et al. J Biol Chem, 2018 Oct 12. PMID 30108174, Free PMC Article
  2. Buschke-Ollendorff syndrome due to a novel LEMD3 mutation - an unusual case of alopecia. Darr-Foit S, et al. J Dtsch Dermatol Ges, 2018 Mar. PMID 29465813
  3. The Role of the Nuclear Envelope Protein MAN1 in Mesenchymal Stem Cell Differentiation. Bermeo S, et al. J Cell Biochem, 2017 Dec. PMID 28449239
  4. RNA recognition motif of LEMD3 as a key player in the pathogenesis of Buschke-Ollendorff syndrome. Takashima S, et al. J Dermatol Sci, 2016 Mar. PMID 26711937
  5. Identification of a novel LEMD3 Y871X mutation in a three-generation family with osteopoikilosis and review of the literature. Zhang Q, et al. J Endocrinol Invest, 2016 Jun. PMID 26694706

See all (100) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Melorheostosis and Osteopoikilosis Clinical and Molecular Description of an Italian Case Series.
    Title: Melorheostosis and Osteopoikilosis Clinical and Molecular Description of an Italian Case Series.
  2. Here we describe the unusual case of a 60-year-old woman with isolated nevus elasticus and a mutation in the LEMD3 (LEM Domain Containing 3) gene.
    Title: Buschke-Ollendorff syndrome due to a novel LEMD3 mutation - an unusual case of alopecia.
  3. analysis of the structural basis for R-SMAD recognition by MAN1 using SMAD2-MAN1 and SMAD1-MAN1 complex structures
    Title: Structural basis for receptor-regulated SMAD recognition by MAN1.
  4. LEMD3 is cleaved by PPM1a into fragments that enter the cytosol to bind SMAD2 and SMAD3, thereby antagonizing signaling initiated by stiffness-triggered activity of TGFbeta.
    Title: LEM domain-containing protein 3 antagonizes TGFβ-SMAD2/3 signaling in a stiffness-dependent manner in both the nucleus and cytosol.
  5. studies demonstrated that lower levels of MAN1 in differentiating MSC are associated with higher osteogenesis and lower adipogenesis. High levels of MAN1 only affected adipogenesis.
    Title: The Role of the Nuclear Envelope Protein MAN1 in Mesenchymal Stem Cell Differentiation.
  6. LAMD3 Y871X mutation is associated with osteopoikilosis.
    Title: Identification of a novel LEMD3 Y871X mutation in a three-generation family with osteopoikilosis and review of the literature.
  7. Letter/Case-Report: novel frameshift mutation in RNA recognition motif of LEMD3 in patient with Buschke-Ollendorff syndrome.
    Title: RNA recognition motif of LEMD3 as a key player in the pathogenesis of Buschke-Ollendorff syndrome.
  8. A novel mutation in LEMD3 splice site results in Buschke-Ollendorff syndrome.
    Title: Novel Somatic Mutation in LEMD3 Splice Site Results in Buschke-Ollendorff Syndrome with Polyostotic Melorheostosis and Osteopoikilosis.
  9. Data indicate that the inner nuclear membrane protein MAN1 directly binds the transcription activator BMAL1 promoter and enhances its transcription.
    Title: Nuclear envelope protein MAN1 regulates clock through BMAL1.
  10. a nuclear envelope-localized mechanism of inactivating TGF-beta signaling in which MAN1 competes with transcription factors for binding to Smad2 and Smad3 and facilitates their dephosphorylation by PPM1A.
    Title: Inhibition of TGF-β signaling at the nuclear envelope: characterization of interactions between MAN1, Smad2 and Smad3, and PPM1A.
Submit: New GeneRIF Correction See all GeneRIFs (25)

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
Dermatofibrosis lenticularis disseminata
MedGen: C0265514 OMIM: 166700 GeneReviews: Not available
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Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2020-10-19)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2020-10-19)

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)

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 DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables U1 snRNP binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in negative regulation of BMP signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of activin receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of transforming growth factor beta receptor signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nuclear inner membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nuclear membrane IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
inner nuclear membrane protein Man1
Names
LEM domain-containing protein 3
LEMD3/MKX fusion
MAN antigen 1
integral inner nuclear membrane 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_016210.2 RefSeqGene

    Range
    5013..83785
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001167614.2 → NP_001161086.1  inner nuclear membrane protein Man1 isoform 2

    See identical proteins and their annotated locations for NP_001161086.1

    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)
    AF112299, AK312473, BX390128
    UniProtKB/Swiss-Prot
    Q9Y2U8
    Conserved Domains (3) summary
    cd12286
    Location:784 → 875
    RRM_Man1; RNA recognition motif in inner nuclear membrane protein Man1 (Man1) and similar proteins
    pfam09402
    Location:535 → 747
    MSC; Man1-Src1p-C-terminal domain
    cl02649
    Location:9 → 51
    LEM; LEM (Lap2/Emerin/Man1) domain found in emerin, lamina-associated polypeptide 2 (LAP2), inner nuclear membrane protein Man1 and similar proteins

  2. NM_014319.5 → NP_055134.2  inner nuclear membrane protein Man1 isoform 1

    See identical proteins and their annotated locations for NP_055134.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AF112299, AK312473, BX390128
    Consensus CDS
    CCDS8972.1
    UniProtKB/Swiss-Prot
    Q9NT47, Q9NYA5, Q9Y2U8
    Related
    ENSP00000308369.2, ENST00000308330.3
    Conserved Domains (3) summary
    cd12286
    Location:785 → 876
    RRM_Man1; RNA recognition motif in inner nuclear membrane protein Man1 (Man1) and similar proteins
    pfam09402
    Location:538 → 748
    MSC; Man1-Src1p-C-terminal domain
    cl02649
    Location:9 → 51
    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_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    65169583..65248355
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    65148505..65227374
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Y2U8.2 GenPept UniProtKB/Swiss-Prot:Q9Y2U8

Gene LinkOut

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