LDB2: LIM Domain Binding 2 - Transcriptional Regulator in Development and Disease
Comprehensive genomic and functional analysis of LDB2, a key cofactor in cell fate determination and cancer.
Gene Information Card
| Symbol | LDB2 |
|---|---|
| Full Name | LIM domain binding 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 4p15.32 |
| NCBI Gene ID | 9079 ncbi.nlm.nih.gov/gene/9079 |
| Ensembl ID | ENSG00000138674 |
| UniProt ID | O43679 |
| OMIM ID | 603450 |
| HGNC ID | 6533 |
| Aliases | CLIM1, LDB1, LDB2, LIM domain binding 2 |
Description
LDB2 (LIM domain binding 2) encodes a member of the LIM domain-binding protein family. The protein functions as a transcriptional cofactor, interacting with LIM-homeodomain (LIM-HD) and LIM-only (LMO) proteins to regulate gene expression during development, particularly in the nervous system and hematopoietic cells. LDB2 can form homo- and heterodimers with LDB1 and modulates chromatin looping and enhancer-promoter interactions. Dysregulation of LDB2 is implicated in cancer progression and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | LDB2 overexpression correlates with poor prognosis; may promote metastasis via transcriptional reprogramming. | PMID: 25691885 |
| Colorectal cancer | LDB2 downregulation associated with tumor progression and epithelial-mesenchymal transition. | PMID: 27323851 |
| Hematologic malignancies | LDB2 interacts with LMO2 in T-cell acute lymphoblastic leukemia; aberrant expression disrupts normal hematopoiesis. | PMID: 10655551 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Heart | 8.3 | Low |
| Lung | 6.1 | Low |
| Liver | 4.2 | Low |
| Kidney | 7.8 | Low |
| Testis | 15.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Embryonic kidney cells; moderate expression |
| HeLa | 8.5 | Cervical cancer cells; moderate expression |
| K562 | 6.3 | Leukemia cells; low expression |
| MCF7 | 12.8 | Breast cancer cells; high expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.101C>T (p.Thr34Met) | Missense | 0.02% (gnomAD) | Unknown functional impact; predicted benign by SIFT |
| c.457G>A (p.Gly153Arg) | Missense | 0.01% (gnomAD) | Located in LIM-interaction domain; may affect protein binding |
| c.1234_1235insA (p.Thr412Asnfs*5) | Frameshift | Rare | Loss-of-function; truncation of C-terminal domain |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein, impairing dimerization and transcriptional coactivation.
Gain of Function (GOF)
Not well characterized; overexpression in certain cancers may act as a gain-of-function by enhancing oncogenic transcriptional programs.
Dominant Negative (DN)
Missense mutations in the LIM-interaction domain may produce proteins that sequester LIM-HD partners without functional activity.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (Reactome: R-HSA-157118)
• Developmental biology (Reactome: R-HSA-1266738)
• Transcriptional regulation by LDB1/LDB2 (Reactome: R-HSA-9616222)
Protein Summary
LDB2 is a 375-amino acid nuclear protein containing a dimerization domain and a LIM-interaction domain. It forms homo- and heterodimers with LDB1 and binds to LIM-homeodomain transcription factors (e.g., LHX3, ISL1) and LIM-only proteins (e.g., LMO2). Through these interactions, LDB2 facilitates chromatin looping and enhancer-promoter communication, regulating genes involved in cell fate specification, neurogenesis, and hematopoiesis. Post-translational modifications include phosphorylation and sumoylation, which modulate its activity and stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LDB2 Knockout HEK293 Cell Line | EDJ-KQ6452 | Human | 9079 | Details Get a Quote |
| LDB2 Knockout HeLa Cell Line | EDJ-KQ55075 | Human | 9079 | Details Get a Quote |
| LDB2 Knockout A-549 Cell Line | EDJ-KQ63555 | Human | 9079 | Details Get a Quote |
| LDB2 Knockout HCT 116 Cell Line | EDJ-KQ72024 | Human | 9079 | Details Get a Quote |
