DLL3 Gene (Delta Like Non-Canonical Notch Ligand 3)
DLL3: Genetics, Expression, and Disease Associations
Gene Information Card
| Symbol | DLL3 |
|---|---|
| Full Name | Delta Like Non-Canonical Notch Ligand 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 19q13.2 |
| NCBI Gene ID | 10683 ncbi.nlm.nih.gov/gene/10683 |
| Ensembl ID | ENSG00000190986 |
| UniProt ID | Q9NYJ7 |
| OMIM ID | 602768 |
| HGNC ID | 2909 |
| Aliases | SCDO1, spondylocostal dysostosis 1, delta-like 3 |
Description
DLL3 encodes a member of the Delta-like family of Notch ligands. Unlike canonical ligands, DLL3 is localized primarily to the Golgi apparatus and inhibits Notch signaling. It plays a critical role in somitogenesis and neuroendocrine differentiation. DLL3 is highly expressed in small cell lung cancer (SCLC) and is a target for antibody-drug conjugates (e.g., rovalpituzumab tesirine).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spondylocostal dysostosis 1 (SCDO1) | Loss-of-function mutations in DLL3 disrupt Notch signaling during somitogenesis, leading to vertebral and rib malformations. | OMIM; PMID: 10677329 |
| Small cell lung cancer (SCLC) | DLL3 is overexpressed on the surface of SCLC cells, promoting tumor growth and neuroendocrine phenotype; targeted by antibody-drug conjugates. | COSMIC; PMID: 26540084 |
| Large cell neuroendocrine carcinoma (LCNEC) | DLL3 expression is elevated in a subset of LCNEC, similar to SCLC, suggesting a potential therapeutic target. | PMID: 29247016 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 0.8 | Low |
| Lung | 0.5 | Low |
| Testis | 0.3 | Low |
| Pancreas | 0.2 | Low |
| Spleen | 0.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NCI-H82 (SCLC) | High | Overexpressed in SCLC cell lines |
| DMS 53 (SCLC) | High | Overexpressed |
| NCI-H524 (SCLC) | High | Overexpressed |
| HEK293 (embryonic kidney) | Low | Basal expression |
| A549 (lung adenocarcinoma) | Low | Minimal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1095_1096delCT (p.Ser366Cysfs*2) | Frameshift | Rare | Loss of function; associated with SCDO1 |
| c.1180C>T (p.Arg394Ter) | Nonsense | Rare | Loss of function; SCDO1 |
| c.1334G>A (p.Arg445His) | Missense | Rare | Loss of function; SCDO1 |
| c.1396C>T (p.Arg466Trp) | Missense | Rare | Loss of function; SCDO1 |
| c.1438G>A (p.Gly480Arg) | Missense | Rare | Loss of function; SCDO1 |
Mutation functional classification
Loss of Function (LOF)
Most DLL3 mutations in SCDO1 are loss-of-function, leading to reduced or absent protein function, disrupting Notch signaling.
Gain of Function (GOF)
No gain-of-function mutations have been reported for DLL3.
Dominant Negative (DN)
Some missense mutations may exert a dominant-negative effect by interfering with wild-type DLL3 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • Notch binding | • calcium ion binding |
| • Golgi apparatus | • plasma membrane |
| • negative regulation of Notch signaling pathway | • cell differentiation |
| • somitogenesis |
Pathways
• Notch signaling pathway
• Developmental biology (somitogenesis)
Protein Summary
DLL3 is a type I transmembrane protein that localizes to the Golgi apparatus and acts as an inhibitor of Notch signaling. It is involved in somitogenesis and neuroendocrine differentiation. In cancer, DLL3 is overexpressed in SCLC and other neuroendocrine tumors, making it a promising therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DLL3 Knockout HEK293 Cell Line | EDJ-KQ416 | Human | 10683 | Details Get a Quote |
| DLL3 Knockout A-549 Cell Line | EDJ-KQ18685 | Human | 10683 | Details Get a Quote |
| DLL3 Knockout HeLa Cell Line | EDJ-KQ18686 | Human | 10683 | Details Get a Quote |
| DLL3 Knockout HCT 116 Cell Line | EDJ-KQ72403 | Human | 10683 | Details Get a Quote |
