DLL4 delta like canonical Notch ligand 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DLL4provided by HGNC
Official Full Name: delta like canonical Notch ligand 4provided by HGNC
Primary source: HGNC:HGNC:2910
See related: Ensembl:ENSG00000128917 MIM:605185; AllianceGenome:HGNC:2910
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: AOS6; delta4; hdelta2
Summary: This gene is a homolog of the Drosophila delta gene. The delta gene family encodes Notch ligands that are characterized by a DSL domain, EGF repeats, and a transmembrane domain. [provided by RefSeq, Jul 2008]
Expression: Broad expression in placenta (RPKM 11.5), fat (RPKM 11.2) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q15.1

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
110	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (40929340..40939073)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (38735323..38745058)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (41221538..41231271)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Delta-like ligand 4 level in colorectal cancer is associated with tumor aggressiveness and clinical outcome.
Title: Delta-like ligand 4 level in colorectal cancer is associated with tumor aggressiveness and clinical outcome.
O-Fucose and Fringe-modified NOTCH1 extracellular domain fragments as decoys to release niche-lodged hematopoietic progenitor cells.
Title: O-Fucose and Fringe-modified NOTCH1 extracellular domain fragments as decoys to release niche-lodged hematopoietic progenitor cells.
Delta-like 4 is required for pulmonary vascular arborization and alveolarization in the developing lung.
Title: Delta-like 4 is required for pulmonary vascular arborization and alveolarization in the developing lung.
Correlation of serum delta-like ligand-4 level with the severity of diabetic retinopathy.
Title: Correlation of serum delta-like ligand-4 level with the severity of diabetic retinopathy.
The expression profile of Jagged1 and Delta-like 4 in hepatocellular carcinoma.
Title: The expression profile of Jagged1 and Delta-like 4 in hepatocellular carcinoma.
Dll4/Notch1 signalling pathway is required in collective invasion of salivary adenoid cystic carcinoma.
Title: Dll4/Notch1 signalling pathway is required in collective invasion of salivary adenoid cystic carcinoma.
DL4-mubeads induce T cell lineage differentiation from stem cells in a stromal cell-free system.
Title: DL4-μbeads induce T cell lineage differentiation from stem cells in a stromal cell-free system.
Anti-Cancer Effect of Melatonin via Downregulation of Delta-like Ligand 4 in Estrogen-Responsive Breast Cancer Cells.
Title: Anti-Cancer Effect of Melatonin via Downregulation of Delta-like Ligand 4 in Estrogen-Responsive Breast Cancer Cells.
NOTCH1 and DLL4 are involved in the human tuberculosis progression and immune response activation.
Title: NOTCH1 and DLL4 are involved in the human tuberculosis progression and immune response activation.
Synergistic antitumor activity of a DLL4/VEGF bispecific therapeutic antibody in combination with irinotecan in gastric cancer.
Title: Synergistic antitumor activity of a DLL4/VEGF bispecific therapeutic antibody in combination with irinotecan in gastric cancer.

Submit: New GeneRIF Correction See all GeneRIFs (131)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Adams-Oliver syndrome 6 MedGen: C4225271 OMIM: 616589 GeneReviews: Adams-Oliver Syndrome	Compare labs

EBI GWAS Catalog

Description
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:70152

UniSTS:465451 (e-PCR)
- UniSTS:465451

Dll4 (e-PCR), detects polymorphism
- UniSTS:465451

PMC316657P1 (e-PCR)
- UniSTS:273027

PMC316657P2 (e-PCR)
- UniSTS:273028

DLL4_593 (e-PCR)
- UniSTS:277166

RH78211 (e-PCR)
- UniSTS:84154

Homology

Homologs of the DLL4 gene: The DLL4 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 443 organisms have orthologs with human gene DLL4
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables Notch binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in Notch signaling involved in heart development	ISS Inferred from Sequence or Structural Similarity more info
involved_in Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in aortic valve morphogenesis	IC Inferred by Curator more info	PubMed
involved_in blood circulation	TAS Traceable Author Statement more info	PubMed
involved_in blood vessel lumenization	IEA Inferred from Electronic Annotation more info
involved_in blood vessel remodeling	ISS Inferred from Sequence or Structural Similarity more info
involved_in branching involved in blood vessel morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cardiac atrium morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cardiac ventricle morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to fibroblast growth factor stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to vascular endothelial growth factor stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dorsal aorta morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of Notch signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in negative regulation of Notch signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell migration involved in sprouting angiogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell migration involved in sprouting angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of endothelial cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in pericardium morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of Notch signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of neural precursor cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of neural retina development	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of neurogenesis	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in ventral spinal cord interneuron fate commitment	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ventricular trabecula myocardium morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in visual perception	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in integral component of membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: delta-like protein 4

Names: delta 4; delta ligand 4; delta-like 4 homolog; delta-like 4 protein; drosophila Delta homolog 4; notch ligand DLL4; notch ligand delta-2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_046974.1 RefSeqGene

Range

5008..14741

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1268

mRNA and Protein(s)

NM_019074.4 → NP_061947.1 delta-like protein 4 precursor

See identical proteins and their annotated locations for NP_061947.1

Status: REVIEWED

Source sequence(s)

AB036931, AI478830, BC106950, DA089757, HY291308

Consensus CDS

CCDS45232.1

UniProtKB/Swiss-Prot

Q9NR61

Related

ENSP00000249749.5, ENST00000249749.7

Conserved Domains (3) summary

cd00054
Location:327 → 360

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

pfam01414
Location:155 → 217

DSL; Delta serrate ligand

pfam07657
Location:27 → 88

MNNL; N terminus of Notch ligand