DLK1 Gene: Delta Like Non-Canonical Notch Ligand 1
A paternally expressed imprinted gene involved in development, adipogenesis, and tumorigenesis.
Gene Information Card
| Symbol | DLK1 |
|---|---|
| Full Name | Delta Like Non-Canonical Notch Ligand 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q32.2 |
| NCBI Gene ID | 8788 ncbi.nlm.nih.gov/gene/8788 |
| Ensembl ID | ENSG00000185559 |
| UniProt ID | P80370 |
| OMIM ID | 176290 |
| HGNC ID | 2907 |
| Aliases | FA1, PREF1, ZOG, pG2, Pref-1, DLK-1, Delta1 |
Description
DLK1 (Delta Like Non-Canonical Notch Ligand 1) is a paternally expressed imprinted gene located on chromosome 14q32.2. It encodes a transmembrane protein containing epidermal growth factor (EGF)-like repeats that functions as a non-canonical inhibitor of Notch signaling. DLK1 plays critical roles in adipogenesis, neuroendocrine differentiation, and skeletal development. It is highly expressed in fetal tissues and certain cancers, including hepatocellular carcinoma and neuroblastoma, where it is associated with poor prognosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Overexpression of DLK1 promotes tumor growth and inhibits apoptosis via Notch pathway modulation | PMID: 23541953; COSMIC gene analysis |
| Neuroblastoma | DLK1 is highly expressed in neuroblastoma cells and correlates with unfavorable histology and MYCN amplification | PMID: 15604238; ClinVar |
| Central precocious puberty | Mutations in DLK1 are associated with imprinted defects leading to early puberty | PMID: 28566283; OMIM 176290 |
| Adipogenesis disorders | DLK1 inhibits adipocyte differentiation; altered expression linked to metabolic syndrome | PMID: 10652251; UniProt |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | 45.2 | High |
| Placenta | 38.7 | High |
| Pancreas | 22.1 | Medium |
| Liver | 15.3 | Medium |
| Brain | 8.4 | Low |
| Skeletal muscle | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 62.5 | High expression; used as model for DLK1 function |
| SK-N-SH (neuroblastoma) | 48.3 | High expression; associated with MYCN amplification |
| MCF7 (breast cancer) | 12.1 | Moderate expression |
| HEK293 (embryonic kidney) | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.632C>T (p.Thr211Met) | Missense | Rare | Unknown functional effect; reported in ClinVar |
| c.1A>G (p.Met1?) | Start loss | Very rare | Likely loss of function; associated with central precocious puberty |
| c.1063_1064insA (p.Thr355Asnfs*12) | Frameshift | Rare | Loss of function; truncation of C-terminal domain |
Mutation functional classification
Loss of Function (LOF)
Frameshift and start-loss mutations that disrupt protein synthesis or truncate the functional domain are classified as loss-of-function.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in DLK1.
Dominant Negative (DN)
Not established for DLK1; the gene is imprinted and monoallelically expressed, reducing dominant-negative potential.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Notch signaling pathway (KEGG: hsa04330)
• Adipogenesis (Reactome: R-HSA-381340)
• Developmental biology (Reactome: R-HSA-1266738)
Protein Summary
The DLK1 protein (UniProt P80370) is a 383-amino-acid transmembrane glycoprotein with six EGF-like repeats in its extracellular domain. It is synthesized as a precursor that is cleaved to generate a soluble form (fetal antigen 1, FA1). DLK1 acts as a non-canonical ligand for Notch receptors, inhibiting Notch signaling and thereby regulating cell differentiation, particularly in adipogenesis and neuroendocrine tissues. The protein is highly expressed during fetal development and is re-expressed in various cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DLK1 Knockout HEK293 Cell Line | EDJ-KQ1971 | Human | 8788 | Details Get a Quote |
| DLK1 Knockout HeLa Cell Line | EDJ-KQ55005 | Human | 8788 | Details Get a Quote |
| DLK1 Knockout A-549 Cell Line | EDJ-KQ63489 | Human | 8788 | Details Get a Quote |
| DLK1 Knockout HCT 116 Cell Line | EDJ-KQ71958 | Human | 8788 | Details Get a Quote |
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