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 Re... See more...

Aliases for LEMD3 Gene

Aliases for LEMD3 Gene

  • LEM Domain Containing 3 2 3 5
  • Inner Nuclear Membrane Protein Man1 2 3 4
  • MAN1 2 3 4
  • LEM Domain-Containing Protein 3 3 4
  • MAN Antigen 1 2 3
  • Integral Inner Nuclear Membrane Protein 3
  • LEMD3/MKX Fusion 3
  • LEMD3 5

External Ids for LEMD3 Gene

Previous GeneCards Identifiers for LEMD3 Gene

  • GC12P063850
  • GC12P065563
  • GC12P062615

Summaries for LEMD3 Gene

Entrez Gene Summary for LEMD3 Gene

  • 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]

GeneCards Summary for LEMD3 Gene

LEMD3 (LEM Domain Containing 3) is a Protein Coding gene. Diseases associated with LEMD3 include Buschke-Ollendorff Syndrome and Melorheostosis With Osteopoikilosis. Among its related pathways are Nuclear Envelope Reassembly and Cell Cycle, Mitotic. Gene Ontology (GO) annotations related to this gene include nucleotide binding. An important paralog of this gene is LEMD2.

UniProtKB/Swiss-Prot Summary for LEMD3 Gene

  • Can function as a specific repressor of TGF-beta, activin, and BMP signaling through its interaction with the R-SMAD proteins. Antagonizes TGF-beta-induced cell proliferation arrest.

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for LEMD3 Gene

Genomics for LEMD3 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for LEMD3 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH12J065168 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 274 +1.7 1718 5.8 BCLAF1 SP1 ZNF207 NCOR1 IKZF1 MYC ZNF580 ZNF592 ATF2 KLF9 LEMD3 ENSG00000276853 HSALNG0091973-001 HSALNG0091973-002 lnc-WIF1-4 ENSG00000250280 MSRB3 TBK1 piR-38351-102
GH12J065821 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 56 +656.8 656809 10.3 ZNF600 SSRP1 ZNF580 ATF2 ZNF223 ZNF10 ZSCAN16 POLR2A ZIC2 ZBTB10 RPSAP52 HMGA2 Hsa-Mir-574_5p-015 lnc-LLPH-22 LEMD3 HMGA2-AS1 TMBIM4 ENSG00000250280 ENSG00000256083 ENSG00000277945
GH12J066168 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 43.5 +999.8 999818 3.2 BCLAF1 SP1 ZNF207 ZNF600 NCOR1 MYC IKZF1 ZNF580 ZNF592 POLR2A TMBIM4 ENSG00000228144 HSALNG0092040 lnc-LLPH-1 LEMD3 MSRB3 LOC100507065 ENSG00000250280 LLPH-DT LLPH
GH12J064403 Promoter/Enhancer 1.7 Ensembl ENCODE CraniofacialAtlas 48.4 -764.6 -764642 3.3 BCLAF1 SP1 ZNF207 IKZF1 MYC ZNF600 SIX5 JUND ATF2 POLR2A HSALNG0091931 XPOT LEMD3 TBK1 SRGAP1 ENSG00000250280 PABPC1P4 ENSG00000255566 C12orf56 HSALNG0091932
GH12J064756 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 33.6 -411.2 -411159 4.5 SP1 ZNF207 ZNF600 IKZF1 ZNF580 ZNF10 POLR2A ZIC2 CHD4 YY1 GNS ENSG00000288591 TBC1D30 TBC1D30-001 TBK1 LEMD3 ENSG00000255566 ENSG00000250280 RF00017-1066 RASSF3
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around LEMD3 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for LEMD3

Top Transcription factor binding sites by QIAGEN in the LEMD3 gene promoter:
  • aMEF-2
  • Ik-2
  • MEF-2
  • MEF-2A
  • MyoD
  • STAT1
  • STAT1alpha
  • STAT2
  • STAT3

Genomic Locations for LEMD3 Gene

Latest Assembly
chr12:65,169,583-65,248,355
(GRCh38/hg38)
Size:
78,773 bases
Orientation:
Plus strand

Previous Assembly
chr12:65,563,363-65,642,135
(GRCh37/hg19 by Entrez Gene)
Size:
78,773 bases
Orientation:
Plus strand

chr12:65,563,351-65,642,107
(GRCh37/hg19 by Ensembl)
Size:
78,757 bases
Orientation:
Plus strand

Genomic View for LEMD3 Gene

Genes around LEMD3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
LEMD3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for LEMD3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LEMD3 Gene

Proteins for LEMD3 Gene

  • Protein details for LEMD3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y2U8-MAN1_HUMAN
    Recommended name:
    Inner nuclear membrane protein Man1
    Protein Accession:
    Q9Y2U8
    Secondary Accessions:
    • Q9NT47
    • Q9NYA5

    Protein attributes for LEMD3 Gene

    Size:
    911 amino acids
    Molecular mass:
    99997 Da
    Quaternary structure:
    • Interacts with SMAD1, SMAD2, SMAD3 and SMAD5. Binds to both phosphorylated and unphosphorylated R-SMADS.

    Three dimensional structures from OCA and Proteopedia for LEMD3 Gene

neXtProt entry for LEMD3 Gene

Post-translational modifications for LEMD3 Gene

  • Ubiquitination at Lys787
  • Modification sites at PhosphoSitePlus

Other Protein References for LEMD3 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for LEMD3 Gene

Domains & Families for LEMD3 Gene

Gene Families for LEMD3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted membrane proteins

Protein Domains for LEMD3 Gene

InterPro:
Blocks:
  • RNA-binding region RNP-1 (RNA recognition motif)
  • LEM-like fold

Suggested Antigen Peptide Sequences for LEMD3 Gene

GenScript: Design optimal peptide antigens:
  • LEM domain-containing protein 3 (MAN1_HUMAN)
genes like me logo Genes that share domains with LEMD3: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for LEMD3 Gene

Function for LEMD3 Gene

Molecular function for LEMD3 Gene

UniProtKB/Swiss-Prot Function:
Can function as a specific repressor of TGF-beta, activin, and BMP signaling through its interaction with the R-SMAD proteins. Antagonizes TGF-beta-induced cell proliferation arrest.

Phenotypes From GWAS Catalog for LEMD3 Gene

Gene Ontology (GO) - Molecular Function for LEMD3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003676 nucleic acid binding IEA --
GO:0003677 DNA binding IEA --
GO:0005515 protein binding IPI 15231748
GO:0031490 chromatin DNA binding IBA 21873635
genes like me logo Genes that share ontologies with LEMD3: view
genes like me logo Genes that share phenotypes with LEMD3: view

Human Phenotype Ontology for LEMD3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LEMD3

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for LEMD3 Gene

Localization for LEMD3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for LEMD3 Gene

Nucleus inner membrane. Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for LEMD3 gene
Compartment Confidence
nucleus 5
plasma membrane 3
extracellular 2
cytoskeleton 2
endoplasmic reticulum 2
mitochondrion 1
endosome 1
cytosol 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nuclear membrane (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for LEMD3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005637 nuclear inner membrane IDA 15647271
GO:0005639 integral component of nuclear inner membrane TAS,IBA 21873635
GO:0016020 membrane TAS 10671519
GO:0016021 integral component of membrane IDA 10671519
genes like me logo Genes that share ontologies with LEMD3: view

Pathways & Interactions for LEMD3 Gene

genes like me logo Genes that share pathways with LEMD3: view

Pathways by source for LEMD3 Gene

1 GeneGo (Thomson Reuters) pathway for LEMD3 Gene
  • Signal transduction Activin A signaling regulation

Gene Ontology (GO) - Biological Process for LEMD3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006997 nucleus organization IEA --
GO:0006998 nuclear envelope organization IBA 21873635
GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway IDA 15647271
GO:0030514 negative regulation of BMP signaling pathway IDA 15647271
GO:0032926 negative regulation of activin receptor signaling pathway IDA 15647271
genes like me logo Genes that share ontologies with LEMD3: view

No data available for SIGNOR curated interactions for LEMD3 Gene

Drugs & Compounds for LEMD3 Gene

No Compound Related Data Available

Transcripts for LEMD3 Gene

mRNA/cDNA for LEMD3 Gene

2 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for LEMD3

Alternative Splicing Database (ASD) splice patterns (SP) for LEMD3 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11 ^ 12a · 12b
SP1: -
SP2:

Relevant External Links for LEMD3 Gene

GeneLoc Exon Structure for
LEMD3

Expression for LEMD3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for LEMD3 Gene

Protein differential expression in normal tissues from HIPED for LEMD3 Gene

This gene is overexpressed in Testis (15.5), Peripheral blood mononuclear cells (11.0), and Pancreas (9.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for LEMD3 Gene



Protein tissue co-expression partners for LEMD3 Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for LEMD3

SOURCE GeneReport for Unigene cluster for LEMD3 Gene:

Hs.744150

mRNA Expression by UniProt/SwissProt for LEMD3 Gene:

Q9Y2U8-MAN1_HUMAN
Tissue specificity: Heart, brain, placenta, lung, liver and skeletal muscle.

Evidence on tissue expression from TISSUES for LEMD3 Gene

  • Liver(4.3)
  • Nervous system(2.3)
  • Skin(2.1)
  • Muscle(2.1)
  • Blood(2)
  • Heart(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for LEMD3 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • integumentary
  • lymphatic
  • nervous
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cranial nerve
  • ear
  • eye
  • head
  • jaw
  • larynx
  • mandible
  • maxilla
  • mouth
  • neck
  • sinus
  • skull
  • tooth
  • vocal cord
Thorax:
  • aorta
  • chest wall
  • clavicle
  • rib
  • rib cage
  • scapula
  • sternum
Abdomen:
  • kidney
Pelvis:
  • pelvis
Limb:
  • ankle
  • arm
  • digit
  • elbow
  • femur
  • fibula
  • finger
  • foot
  • forearm
  • hand
  • hip
  • humerus
  • knee
  • lower limb
  • radius
  • shin
  • shoulder
  • thigh
  • tibia
  • toe
  • ulna
  • upper limb
  • wrist
General:
  • blood vessel
  • lymph node
  • lymph vessel
  • peripheral nervous system
  • skin
  • spinal column
  • vertebrae
genes like me logo Genes that share expression patterns with LEMD3: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for LEMD3 Gene

Orthologs for LEMD3 Gene

This gene was present in the common ancestor of animals.

Orthologs for LEMD3 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia LEMD3 29 30
  • 99.74 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia LEMD3 29 30
  • 92.85 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia LEMD3 29 30
  • 88.53 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Lemd3 29
  • 86.5 (n)
Mouse
(Mus musculus)
Mammalia Lemd3 29 16 30
  • 86.23 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia LEMD3 30
  • 84 (a)
OneToOne
Chicken
(Gallus gallus)
Aves LEMD3 29 30
  • 80.45 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia LEMD3 30
  • 65 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia lemd3 29
  • 66.82 (n)
African clawed frog
(Xenopus laevis)
Amphibia XMAN1 29
Zebrafish
(Danio rerio)
Actinopterygii lemd3 29 30
  • 64.46 (n)
OneToOne
Worm
(Caenorhabditis elegans)
Secernentea lem-2 30
  • 20 (a)
OneToOne
Species where no ortholog for LEMD3 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Oppossum (Monodelphis domestica)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for LEMD3 Gene

ENSEMBL:
Gene Tree for LEMD3 (if available)
TreeFam:
Gene Tree for LEMD3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for LEMD3: view image
Alliance of Genome Resources:
Additional Orthologs for LEMD3

Paralogs for LEMD3 Gene

Paralogs for LEMD3 Gene

genes like me logo Genes that share paralogs with LEMD3: view

Variants for LEMD3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for LEMD3 Gene

SNP ID Clinical significance and condition Chr 12 pos Variation AA Info Type
1002285 Uncertain Significance: not provided 65,246,285(+) G/A
NM_014319.5(LEMD3):c.2696G>A (p.Arg899His)
MISSENSE
1004584 Uncertain Significance: not provided 65,169,645(+) C/T
NM_014319.5(LEMD3):c.49C>T (p.Leu17Phe)
MISSENSE
1007350 Uncertain Significance: not provided 65,246,291(+) G/A
NM_014319.5(LEMD3):c.2702G>A (p.Arg901Gln)
MISSENSE
1011494 Uncertain Significance: not provided 65,239,938(+) T/C
NM_014319.5(LEMD3):c.1931T>C (p.Met644Thr)
MISSENSE
1021128 Uncertain Significance: not provided 65,170,750(+) C/T
NM_014319.5(LEMD3):c.1154C>T (p.Ser385Phe)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for LEMD3 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for LEMD3 Gene

Variant ID Type Subtype PubMed ID
nsv1144631 CNV deletion 24896259
nsv522671 CNV loss 19592680
nsv832445 CNV gain 17160897
nsv952197 CNV duplication 24416366

Variation tolerance for LEMD3 Gene

Residual Variation Intolerance Score: 22.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.85; 34.74% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for LEMD3 Gene

Human Gene Mutation Database (HGMD)
LEMD3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
LEMD3
Leiden Open Variation Database (LOVD)
LEMD3

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LEMD3 Gene

Disorders for LEMD3 Gene

MalaCards: The human disease database

(26) MalaCards diseases for LEMD3 Gene - From: OMI, CVR, GTR, ORP, COP, and GCD

Disorder Aliases PubMed IDs
buschke-ollendorff syndrome
  • bos
melorheostosis with osteopoikilosis
  • mixed sclerosing bone dystrophy
osteopoikilosis
  • osteopathia condensans disseminata
arteriovenous malformations of the brain
  • bavm
melorheostosis
  • candle wax disease
- elite association - COSMIC cancer census association via MalaCards
Search LEMD3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

MAN1_HUMAN
  • Buschke-Ollendorff syndrome (BOS) [MIM:166700]: A disease characterized by osteopoikilosis and disseminated connective-tissue nevi. Osteopoikilosis is a skeletal dysplasia characterized by a symmetric but unequal distribution of multiple hyperostotic areas in different parts of the skeleton. Elastic-type nevi (juvenile elastoma) and collagen-type nevi (dermatofibrosis lenticularis disseminata) have been described in BOS. Skin or bony lesions can be absent in some family members, whereas other relatives may have both. {ECO:0000269 PubMed:15489854, ECO:0000269 PubMed:19438932}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for LEMD3

genes like me logo Genes that share disorders with LEMD3: view

No data available for Genatlas for LEMD3 Gene

Publications for LEMD3 Gene

  1. Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis. (PMID: 15489854) Hellemans J … Mortier GR (Nature genetics 2004) 2 3 4 72
  2. MAN1, an inner nuclear membrane protein that shares the LEM domain with lamina-associated polypeptide 2 and emerin. (PMID: 10671519) Lin F … Worman HJ (The Journal of biological chemistry 2000) 2 3 4 22
  3. Novel and recurrent germline LEMD3 mutations causing Buschke-Ollendorff syndrome and osteopoikilosis but not isolated melorheostosis. (PMID: 19438932) Zhang Y … Wordsworth BP (Clinical genetics 2009) 3 4 72
  4. Deactivating germline mutations in LEMD3 cause osteopoikilosis and Buschke-Ollendorff syndrome, but not sporadic melorheostosis. (PMID: 17087626) Mumm S … Whyte MP (Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 2007) 3 22 72
  5. The carboxyl-terminal nucleoplasmic region of MAN1 exhibits a DNA binding winged helix domain. (PMID: 16648637) Caputo S … Zinn-Justin S (The Journal of biological chemistry 2006) 3 4 22

Products for LEMD3 Gene

Sources for LEMD3 Gene