LEMD3
LEM domain containing 3
Gene Information Card
| Symbol | LEMD3 |
|---|---|
| Full Name | LEM domain containing 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 12q14.3 |
| NCBI Gene ID | 23592 ncbi.nlm.nih.gov/gene/23592 |
| Ensembl ID | ENSG00000174106 |
| UniProt ID | Q9Y2U8 |
| OMIM ID | 607844 |
| HGNC ID | 28887 |
| Aliases | MAN1, LEMD3, OTTHUMP00000016423 |
Description
LEMD3 encodes an inner nuclear membrane protein, MAN1, which belongs to the LEM (LAP2, emerin, MAN1) family. MAN1 interacts with lamins and chromatin, and negatively regulates TGF-beta, activin, and BMP signaling by binding to receptor-activated SMAD proteins. Loss-of-function mutations in LEMD3 cause osteopoikilosis, Buschke-Ollendorff syndrome, and melorheostosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Osteopoikilosis | Loss-of-function mutations in LEMD3 impair SMAD antagonism, leading to increased TGF-beta/BMP signaling and abnormal bone formation. | OMIM #166700; multiple reports in NCBI and ClinVar |
| Buschke-Ollendorff syndrome | Heterozygous LEMD3 mutations cause dominant inheritance of osteopoikilosis and connective tissue nevi (dermatofibrosis lenticularis disseminata). | OMIM #166700; HGNC |
| Melorheostosis | Somatic LEMD3 mutations (postzygotic) in affected bone lesions result in hyperostosis. | OMIM #155950; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone | 10.2 | Medium |
| Skin | 8.5 | Medium |
| Heart | 6.1 | Low |
| Liver | 5.3 | Low |
| Brain | 3.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.4 | Cervical cancer cell line |
| HepG2 | 9.8 | Hepatocellular carcinoma |
| A549 | 7.6 | Lung adenocarcinoma |
| MCF7 | 6.2 | Breast cancer |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.205C>T (p.Arg69*) | Nonsense | Rare | Loss of function; truncation of MAN1 protein |
| c.778_779delCT | Frameshift | Rare | Loss of function; premature stop codon |
| c.1A>G (p.Met1?) | Missense (start loss) | Rare | Loss of function; translation initiation failure |
Mutation functional classification
Loss of Function (LOF)
Most LEMD3 mutations are loss-of-function, leading to haploinsufficiency or complete loss of MAN1, which reduces inhibition of TGF-beta/BMP signaling.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
Not described; heterozygous mutations cause disease via haploinsufficiency.
View complete mutation data：
Gene Ontology (GO)
| • nuclear inner membrane | • protein binding |
| • SMAD binding | • negative regulation of BMP signaling pathway |
| • negative regulation of transforming growth factor beta receptor signaling pathway | • chromatin binding |
Pathways
• TGF-beta signaling pathway (KEGG hsa04350)
• BMP signaling pathway (Reactome R-HSA-201451)
Protein Summary
MAN1 is a 911-amino acid inner nuclear membrane protein with two transmembrane domains and a conserved LEM domain. It directly binds receptor-activated SMADs (SMAD1, SMAD2, SMAD3, SMAD5) and recruits them to the nuclear envelope, preventing their nuclear accumulation and transcriptional activity. This negative regulation is critical for normal bone and connective tissue development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LEMD3 Knockout HEK293 Cell Line | EDJ-KQ8093 | Human | 23592 | Details Get a Quote |
| LEMD3 Knockout A-549 Cell Line | EDJ-KQ33953 | Human | 23592 | Details Get a Quote |
| LEMD3 Knockout HCT 116 Cell Line | EDJ-KQ33954 | Human | 23592 | Details Get a Quote |
| LEMD3 Knockout HeLa Cell Line | EDJ-KQ32615 | Human | 23592 | Details Get a Quote |
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