LDB3
Chr 10ADARLIM domain binding 3
Also known as: CMD1C, CMD2L, CMH24, CMPD3, CYPHER, LDB3Z1, LDB3Z4, LVNC3
The encoded protein functions as an adapter in striated muscle, coupling protein kinase C-mediated signaling to the cytoskeleton through its PDZ and LIM domains and interactions with alpha-actinin-2 and myozenin family members. Mutations cause various forms of cardiomyopathy (dilated, hypertrophic, and left ventricular noncompaction) and myofibrillar myopathy, primarily affecting cardiac and skeletal muscle. The gene shows both autosomal dominant and autosomal recessive inheritance patterns.
Disputed — evidence questions this relationship
4 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
600 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 16 | 0 | 11 | 0 | 27 |
Likely Pathogenic | 4 | 0 | 0 | 0 | 4 |
VUS | 18 | 320 | 47 | 19 | 404 |
Likely Benign | 0 | 5 | 54 | 80 | 139 |
Benign | 0 | 1 | 9 | 1 | 11 |
Conflicting | — | 10 | |||
| Total | 38 | 326 | 121 | 100 | 595 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
LDB3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation
RECRUITINGRegistry Study of Pregnancy and Breast Cancer
ACTIVE NOT RECRUITINGORACLE: A Long-term Follow-up Study to Evaluate the Safety of GT005 in Participants With Geographic Atrophy Secondary to Age-related Macular Degeneration Treated in a Gyroscope-sponsored Antecedent Study
ENROLLING BY INVITATIONExternal Resources
Links to major genomics databases and tools