DLL4 Gene (Protein Coding)

Delta Like Canonical Notch Ligand 4

GC15P040929
GIFtS:
47
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] See more...

Aliases for DLL4 Gene

Aliases for DLL4 Gene

  • Delta Like Canonical Notch Ligand 4 2 3 5
  • Drosophila Delta Homolog 4 3 4
  • Delta-Like Protein 4 3 4
  • Delta4 3 4
  • Delta-Like 4 Homolog (Drosophila) 2
  • Delta-Like 4 (Drosophila) 2
  • Delta-Like 4 Homolog 3
  • Delta-Like 4 Protein 3
  • Notch Ligand Delta-2 3
  • Notch Ligand DLL4 3
  • Delta Ligand 4 3
  • Delta 4 3
  • Hdelta2 3
  • AOS6 3

External Ids for DLL4 Gene

Previous GeneCards Identifiers for DLL4 Gene

  • GC15P036589
  • GC15P034117
  • GC15P038800
  • GC15P038937
  • GC15P039008
  • GC15P041221
  • GC15P018070

Summaries for DLL4 Gene

Entrez Gene Summary for DLL4 Gene

  • 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]

GeneCards Summary for DLL4 Gene

DLL4 (Delta Like Canonical Notch Ligand 4) is a Protein Coding gene. Diseases associated with DLL4 include Adams-Oliver Syndrome 6 and Adams-Oliver Syndrome. Among its related pathways are NOTCH2 Activation and Transmission of Signal to the Nucleus and Th17 cell differentiation. Gene Ontology (GO) annotations related to this gene include calcium ion binding and Notch binding. An important paralog of this gene is DLL1.

UniProtKB/Swiss-Prot Summary for DLL4 Gene

  • Involved in the Notch signaling pathway as Notch ligand (PubMed:11134954). Activates NOTCH1 and NOTCH4. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting (PubMed:20616313). Essential for retinal progenitor proliferation. Required for suppressing rod fates in late retinal progenitors as well as for proper generation of other retinal cell types (By similarity). During spinal cord neurogenesis, inhibits V2a interneuron fate (PubMed:17728344).

Gene Wiki entry for DLL4 Gene

Additional gene information for DLL4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for DLL4 Gene

Genomics for DLL4 Gene

GeneHancer (GH) Regulatory Elements for DLL4 Gene

Promoters and enhancers for DLL4 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around DLL4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the DLL4 gene promoter:
  • ATF
  • GATA-2
  • HEN1
  • Nkx2-5
  • p53
  • Pax-5
  • STAT3

Genomic Locations for DLL4 Gene

Genomic Locations for DLL4 Gene
chr15:40,929,333-40,939,073
(GRCh38/hg38)
Size:
9,741 bases
Orientation:
Plus strand
chr15:41,221,531-41,231,258
(GRCh37/hg19)
Size:
9,728 bases
Orientation:
Plus strand

Genomic View for DLL4 Gene

Genes around DLL4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DLL4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DLL4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for DLL4 Gene

Proteins for DLL4 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for DLL4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NR61-DLL4_HUMAN
    Recommended name:
    Delta-like protein 4
    Protein Accession:
    Q9NR61
    Secondary Accessions:
    • Q3KP23
    • Q9NQT9

    Protein attributes for DLL4 Gene

    Size:
    685 amino acids
    Molecular mass:
    74605 Da
    Quaternary structure:
    • Interacts with NOTCH4. Interacts (via N-terminal DSL and MNNL domains) with NOTCH1 (via EGF-like domains).

    Three dimensional structures from OCA and Proteopedia for DLL4 Gene

neXtProt entry for DLL4 Gene

Protein Expression for DLL4 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for DLL4 Gene

  • Glycosylation at Asn108, Asn183, Asn205, and Asn393
  • Modification sites at PhosphoSitePlus

Other Protein References for DLL4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for DLL4

No data available for DME Specific Peptides for DLL4 Gene

Domains & Families for DLL4 Gene

Gene Families for DLL4 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted membrane proteins

Protein Domains for DLL4 Gene

Blocks:
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for DLL4 Gene

GenScript: Design optimal peptide antigens:
  • Drosophila Delta homolog 4 (DLL4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9NR61

UniProtKB/Swiss-Prot:

DLL4_HUMAN :
  • The Delta-Serrate-Lag2 (DSL) domain is required for binding to the Notch receptor.
Domain:
  • The Delta-Serrate-Lag2 (DSL) domain is required for binding to the Notch receptor.
genes like me logo Genes that share domains with DLL4: view

Function for DLL4 Gene

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  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for DLL4 Gene

UniProtKB/Swiss-Prot Function:
Involved in the Notch signaling pathway as Notch ligand (PubMed:11134954). Activates NOTCH1 and NOTCH4. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting (PubMed:20616313). Essential for retinal progenitor proliferation. Required for suppressing rod fates in late retinal progenitors as well as for proper generation of other retinal cell types (By similarity). During spinal cord neurogenesis, inhibits V2a interneuron fate (PubMed:17728344).

LifeMap Function Summary for DLL4 Gene

During embryonic development, DLL4 as signaling molecule is secreted from the following cells
It affects the following cells:

Phenotypes From GWAS Catalog for DLL4 Gene

Gene Ontology (GO) - Molecular Function for DLL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005112 Notch binding TAS,IBA 21873635
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IPI 24025447
genes like me logo Genes that share ontologies with DLL4: view
genes like me logo Genes that share phenotypes with DLL4: view

Human Phenotype Ontology for DLL4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for DLL4 Gene

MGI Knock Outs for DLL4:

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for DLL4 Gene

Localization for DLL4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DLL4 Gene

Cell membrane; Single-pass type I membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for DLL4 gene
Compartment Confidence
plasma membrane 4
extracellular 2
cytoskeleton 1
nucleus 1
lysosome 1
mitochondrion 0

Gene Ontology (GO) - Cellular Components for DLL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane IBA,TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with DLL4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for DLL4 Gene

Pathways & Interactions for DLL4 Gene

genes like me logo Genes that share pathways with DLL4: view

SIGNOR curated interactions for DLL4 Gene

Activates:
Inactivates:
Is activated by:

Gene Ontology (GO) - Biological Process for DLL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II ISS --
GO:0001525 angiogenesis ISS --
GO:0001569 branching involved in blood vessel morphogenesis IEA,ISS --
GO:0001974 blood vessel remodeling ISS,IEA --
GO:0003180 aortic valve morphogenesis IC 26491108
genes like me logo Genes that share ontologies with DLL4: view

Drugs & Compounds for DLL4 Gene

Products:

  1. Drug

(19) Drugs for DLL4 Gene - From: ClinicalTrials and DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Nicotinamide Approved, Investigational Pharma 519,519
Niacin Approved, Investigational Nutra Unknown, Agonist, Full agonist 523,523
Folic acid Approved, Vet_approved Nutra 4687
Demcizumab Investigational Pharma 0
Angiogenesis Inhibitors Pharma 4808

(1) Additional Compounds for DLL4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with DLL4: view

Transcripts for DLL4 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for DLL4 Gene

(1) REFSEQ mRNAs :
(12) Additional mRNA sequences :
(84) Selected AceView cDNA sequences:
(3) Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for DLL4 Gene

No ASD Table

Relevant External Links for DLL4 Gene

GeneLoc Exon Structure for
DLL4
ECgene alternative splicing isoforms for
DLL4

Expression for DLL4 Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for DLL4 Gene

mRNA expression in normal human tissues for DLL4 Gene
mRNA expression by BioGPS for DLL4 GenemRNA expression by GTEx for DLL4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for DLL4 Gene

This gene is overexpressed in Fetal gut (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for DLL4 Gene



Protein tissue co-expression partners for DLL4 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of DLL4 Gene:

DLL4

SOURCE GeneReport for Unigene cluster for DLL4 Gene:

Hs.511076

mRNA Expression by UniProt/SwissProt for DLL4 Gene:

Q9NR61-DLL4_HUMAN
Tissue specificity: Expressed in vascular endothelium.

Evidence on tissue expression from TISSUES for DLL4 Gene

  • Nervous system(4.3)
  • Heart(2.8)
  • Bone marrow(2.1)
  • Lung(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for DLL4 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Regions:
Head and neck:
  • brain
  • cerebellum
  • cerebrospinal fluid
  • chin
  • cranial nerve
  • ear
  • eye
  • eyelid
  • face
  • forehead
  • head
  • jaw
  • lip
  • mandible
  • maxilla
  • meninges
  • mouth
  • nose
  • outer ear
  • scalp
  • skull
Thorax:
  • aorta
  • breast
  • chest wall
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • sternum
Abdomen:
  • abdominal wall
Pelvis:
  • placenta
  • uterus
Limb:
  • ankle
  • digit
  • finger
  • foot
  • hand
  • lower limb
  • nail
  • toe
  • upper limb
General:
  • blood
  • blood vessel
  • hair
  • peripheral nervous system
  • skin
  • spinal cord
genes like me logo Genes that share expression patterns with DLL4: view

No data available for mRNA differential expression in normal tissues for DLL4 Gene

Orthologs for DLL4 Gene

This gene was present in the common ancestor of animals.

Orthologs for DLL4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia DLL4 33 32
  • 99.51 (n)
 OneToOne
dog
(Canis familiaris)
 Mammalia DLL4 33 32
  • 90.85 (n)
 OneToOne
cow
(Bos Taurus)
 Mammalia DLL4 33 32
  • 90.36 (n)
 OneToOne
rat
(Rattus norvegicus)
 Mammalia Dll4 32
  • 86.86 (n)
mouse
(Mus musculus)
 Mammalia Dll4 17 33 32
  • 86.07 (n)
oppossum
(Monodelphis domestica)
 Mammalia DLL4 33
  • 81 (a)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia DLL4 33
  • 75 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves DLL4 33 32
  • 71.44 (n)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia DLL4 33
  • 61 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia dll4 32
  • 64.87 (n)
zebrafish
(Danio rerio)
 Actinopterygii dll4 33 32
  • 62.47 (n)
 OneToOne
fruit fly
(Drosophila melanogaster)
 Insecta CG15388 34
  • 38 (a)
C901 34
  • 37 (a)
Dl 33 34
  • 32 (a)
 OneToMany
worm
(Caenorhabditis elegans)
 Secernentea apx-1 34
  • 35 (a)
sea squirt
(Ciona savignyi)
 Ascidiacea CSA.7799 33
  • 32 (a)
 ManyToMany
-- 33
  • 24 (a)
 ManyToMany
Species where no ortholog for DLL4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for DLL4 Gene

ENSEMBL:
Gene Tree for DLL4 (if available)
TreeFam:
Gene Tree for DLL4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for DLL4: view image

Paralogs for DLL4 Gene

Paralogs for DLL4 Gene

(4) SIMAP similar genes for DLL4 Gene using alignment to 1 proteins:

  • DLL4_HUMAN
genes like me logo Genes that share paralogs with DLL4: view

Variants for DLL4 Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations from dbSNP and Humsavar for DLL4 Gene

SNP ID Clin Chr 15 pos Variation AA Info Type
rs1247027543 pathogenic, Adams-Oliver syndrome 6 40,936,384(+) G/A coding_sequence_variant, missense_variant
rs1555392837 uncertain-significance, Adams-Oliver syndrome 6 40,930,044(+) CTTC/C coding_sequence_variant, inframe_deletion
rs1555393027 likely-pathogenic, Adams-Oliver syndrome 6 40,934,646(+) A/C coding_sequence_variant, missense_variant
rs1555393082 uncertain-significance, Adams-Oliver syndrome 6 40,935,122(+) G/C intron_variant
rs1555393125 pathogenic, Adams-Oliver syndrome 6 40,936,297(+) G/C coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for DLL4 Gene

Variant ID Type Subtype PubMed ID
nsv1504 CNV insertion 18451855

Variation tolerance for DLL4 Gene

Residual Variation Intolerance Score: 10.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.25; 24.95% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DLL4 Gene

Human Gene Mutation Database (HGMD)
DLL4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
DLL4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for DLL4 Gene

Disorders for DLL4 Gene

MalaCards: The human disease database

(5) MalaCards diseases for DLL4 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
adams-oliver syndrome 6
  • aos6
adams-oliver syndrome
  • aos
aplasia cutis congenita
  • congenital defect of skull and scalp
oliver syndrome
  • postaxial polydactyly and mental retardation
cerebral cavernous malformations
  • cam
- elite association - COSMIC cancer census association via MalaCards
Search DLL4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

DLL4_HUMAN
  • Adams-Oliver syndrome 6 (AOS6) [MIM:616589]: A form of Adams-Oliver syndrome, a disorder characterized by the congenital absence of skin (aplasia cutis congenita) in combination with transverse limb defects. Aplasia cutis congenita can be located anywhere on the body, but in the vast majority of the cases, it is present on the posterior parietal region where it is often associated with an underlying defect of the parietal bones. Limb abnormalities are typically limb truncation defects affecting the distal phalanges or entire digits (true ectrodactyly). Only rarely, metatarsals/metacarpals or more proximal limb structures are also affected. Apart from transverse limb defects, syndactyly, most commonly of second and third toes, can also be observed. The clinical features are highly variable and can also include cardiovascular malformations, brain abnormalities and vascular defects such as cutis marmorata and dilated scalp veins. {ECO:0000269 PubMed:26299364}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for DLL4

ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with DLL4: view

No data available for Genatlas for DLL4 Gene

Publications for DLL4 Gene

  1. Dll4, a novel Notch ligand expressed in arterial endothelium. (PMID: 10837024) Shutter JR … Stark KL (Genes & development 2000) 2 3 4 23 56
  2. Heterozygous Loss-of-Function Mutations in DLL4 Cause Adams-Oliver Syndrome. (PMID: 26299364) Meester JA … Wuyts W (American journal of human genetics 2015) 3 4 56
  3. Integrin cytoplasmic domain-associated protein-1 attenuates sprouting angiogenesis. (PMID: 20616313) Brütsch R … Fischer A (Circulation research 2010) 3 4 56
  4. [Influence of Delta-like ligand 4/Notch signal transduction pathway upon the biological behavior of human umbilical vein endothelial cells]. (PMID: 20193271) Chen L … Li T (Zhonghua yi xue za zhi 2009) 3 23 56
  5. Regulation of CXCR4 by the Notch ligand delta-like 4 in endothelial cells. (PMID: 18339870) Williams CK … Harris AL (Cancer research 2008) 3 23 56

ExternalLinks

View latest publications for DLL4 gene in Mastermind

Products for DLL4 Gene

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