LDB3 Gene (LIM Domain Binding 3)
Key regulator of sarcomere assembly and Z-disc structure; implicated in cardiomyopathies and myofibrillar myopathy
Gene Information Card
| Symbol | LDB3 |
|---|---|
| Full Name | LIM domain binding 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q23.2 |
| NCBI Gene ID | 11155 ncbi.nlm.nih.gov/gene/11155 |
| Ensembl ID | ENSG00000122367 |
| UniProt ID | O75112 |
| OMIM ID | 605906 |
| HGNC ID | 15710 |
| Aliases | ZASP, CMD1C, CMH24, KIAA0613, LDB3Z1, LDB3Z2, LDB3Z3, LDB3Z4, LDB3Z5, LDB3Z6, LDB3Z7, LDB3Z8, LDB3Z9, LDB3Z10, LDB3Z11, LDB3Z12, LDB3Z13, LDB3Z14, LDB3Z15, LDB3Z16, LDB3Z17, LDB3Z18, LDB3Z19, LDB3Z20, LDB3Z21, LDB3Z22, LDB3Z23, LDB3Z24, LDB3Z25, LDB3Z26, LDB3Z27, LDB3Z28, LDB3Z29, LDB3Z30, LDB3Z31, LDB3Z32, LDB3Z33, LDB3Z34, LDB3Z35, LDB3Z36, LDB3Z37, LDB3Z38, LDB3Z39, LDB3Z40, LDB3Z41, LDB3Z42, LDB3Z43, LDB3Z44, LDB3Z45, LDB3Z46, LDB3Z47, LDB3Z48, LDB3Z49, LDB3Z50, LDB3Z51, LDB3Z52, LDB3Z53, LDB3Z54, LDB3Z55, LDB3Z56, LDB3Z57, LDB3Z58, LDB3Z59, LDB3Z60, LDB3Z61, LDB3Z62, LDB3Z63, LDB3Z64, LDB3Z65, LDB3Z66, LDB3Z67, LDB3Z68, LDB3Z69, LDB3Z70, LDB3Z71, LDB3Z72, LDB3Z73, LDB3Z74, LDB3Z75, LDB3Z76, LDB3Z77, LDB3Z78, LDB3Z79, LDB3Z80, LDB3Z81, LDB3Z82, LDB3Z83, LDB3Z84, LDB3Z85, LDB3Z86, LDB3Z87, LDB3Z88, LDB3Z89, LDB3Z90, LDB3Z91, LDB3Z92, LDB3Z93, LDB3Z94, LDB3Z95, LDB3Z96, LDB3Z97, LDB3Z98, LDB3Z99, LDB3Z100 |
Description
The LDB3 gene encodes the LIM domain binding 3 protein, also known as ZASP (Z-band alternatively spliced PDZ-motif protein). This protein is a component of the sarcomere Z-disc, where it plays a critical role in maintaining structural integrity and mediating protein-protein interactions. LDB3 is essential for normal cardiac and skeletal muscle function. Mutations in this gene are associated with various forms of cardiomyopathy and myofibrillar myopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dilated cardiomyopathy (CMD1C) | Disruption of Z-disc integrity leading to impaired contractility and cardiac dilation | ClinVar, OMIM |
| Hypertrophic cardiomyopathy (CMH24) | Altered sarcomere assembly and signaling, causing myocardial hypertrophy | ClinVar, OMIM |
| Myofibrillar myopathy (MFM) | Aggregation of Z-disc proteins and myofibrillar disorganization, leading to muscle weakness | ClinVar, OMIM |
| Left ventricular noncompaction cardiomyopathy | Abnormal myocardial development due to defective Z-disc function | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart muscle | 58.2 | High |
| Skeletal muscle | 45.1 | High |
| Esophagus | 12.3 | Medium |
| Adipose tissue | 8.7 | Medium |
| Brain cortex | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cardiomyocytes (AC16) | 62.5 | High expression |
| Skeletal muscle myoblasts (HSMM) | 48.9 | High expression |
| HeLa | 3.2 | Low expression |
| HEK293 | 1.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.196C>T (p.Arg66Trp) | Missense | Rare | Alters PDZ domain, associated with dilated cardiomyopathy |
| c.239G>A (p.Arg80His) | Missense | Rare | Impairs Z-disc binding, linked to hypertrophic cardiomyopathy |
| c.634C>T (p.Arg212Trp) | Missense | Rare | Causes myofibrillar myopathy with cardiac involvement |
| c.1003G>A (p.Ala335Thr) | Missense | Rare | Associated with left ventricular noncompaction |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., truncations) reduce Z-disc stability, leading to dilated cardiomyopathy.
Gain of Function (GOF)
Gain-of-function mutations (e.g., certain missense variants) may enhance protein aggregation, contributing to hypertrophic cardiomyopathy.
Dominant Negative (DN)
Dominant-negative mutations (e.g., PDZ domain missense) disrupt wild-type LDB3 function, causing myofibrillar myopathy.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Cardiac muscle contraction (KEGG: hsa04260)
• Striated muscle contraction (Reactome: R-HSA-390522)
• Formation of the sarcomere (Reactome: R-HSA-5250913)
Protein Summary
The LDB3 protein (ZASP) is a 727-amino acid protein containing an N-terminal PDZ domain and three C-terminal LIM domains. It localizes to the Z-disc of sarcomeres in cardiac and skeletal muscle, where it interacts with alpha-actinin and other structural proteins to maintain sarcomere integrity. Alternative splicing generates multiple isoforms with tissue-specific functions. Mutations in LDB3 disrupt Z-disc assembly and signaling, leading to cardiomyopathy and myopathy.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LDB3 Knockout HEK293 Cell Line | EDJ-KQ77917 | Human | 11155 | Details Get a Quote |
| LDB3 Knockout HeLa Cell Line | EDJ-KQ77918 | Human | 11155 | Details Get a Quote |
| LDB3 Knockout A-549 Cell Line | EDJ-KQ77919 | Human | 11155 | Details Get a Quote |
| LDB3 Knockout HCT 116 Cell Line | EDJ-KQ77920 | Human | 11155 | Details Get a Quote |
