LDB3
Chr 10ADARLIM domain binding 3
Also known as: CMD1C, CMD2L, CMH24, CMPD3, CYPHER, LDB3Z1, LDB3Z4, LVNC3
This gene encodes a PDZ domain-containing protein. PDZ motifs are modular protein-protein interaction domains consisting of 80-120 amino acid residues. PDZ domain-containing proteins interact with each other in cytoskeletal assembly or with other proteins involved in targeting and clustering of membrane proteins. The protein encoded by this gene interacts with alpha-actinin-2 through its N-terminal PDZ domain and with protein kinase C via its C-terminal LIM domains. The LIM domain is a cysteine-rich motif defined by 50-60 amino acids containing two zinc-binding modules. This protein also interacts with all three members of the myozenin family. Mutations in this gene have been associated with myofibrillar myopathy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding different isoforms have been identified; all isoforms have N-terminal PDZ domains while only longer isoforms (1, 2 and 5) have C-terminal LIM domains. [provided by RefSeq, Jan 2010]
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 — mechanism propensity
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
1605 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 | 26 | 2 | 3 | 0 | 31 |
Likely Pathogenic | 6 | 4 | 0 | 0 | 10 |
VUS | 34 | 707 | 102 | 41 | 884 |
Likely Benign | 0 | 38 | 144 | 269 | 451 |
Benign | 0 | 5 | 68 | 11 | 84 |
Conflicting | — | 140 | |||
| Total | 66 | 756 | 317 | 321 | 1,600 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →38 pathogenic / likely-pathogenic (of 49) ClinVar copy-number / structural variants overlap LDB3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →
Protein Context — Lollipop Plot
LDB3 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
ORACLE: 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 INVITATIONRegistry Study of Pregnancy and Breast Cancer
ACTIVE NOT RECRUITINGORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation
RECRUITINGExternal Resources
Links to major genomics databases and tools