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Aliases for DLL4 Gene

Aliases for DLL4 Gene

  • Delta Like Canonical Notch Ligand 4 2 3 5
  • Drosophila Delta Homolog 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
  • Delta-Like Protein 4 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 Aplasia Cutis Congenita, Nonsyndromic. Among its related pathways are NOTCH2 Activation and Transmission of Signal to the Nucleus and HIV Life Cycle. GO annotations related to this gene include calcium ion binding and Notch binding. An important paralog of this gene is DLL1.

UniProtKB/Swiss-Prot 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

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for DLL4 Gene

Genomics for DLL4 Gene

Regulatory Elements for DLL4 Gene

Enhancers for DLL4 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH15F041016 0.8 Ensembl ENCODE 11.6 +89.0 89009 3.3 CTCF RAD21 GATA3 CTBP1 POLR2A SCRT2 SMC3 FOS CREM SCRT1 ENSG00000251161 VPS18 DLL4 NDUFAF1 CHAC1 SPINT1 CHP1 EXD1 RTF1 INO80
GH15F041014 0.5 ENCODE 11.6 +85.9 85882 0.7 MTA2 ENSG00000251161 VPS18 DLL4 CHAC1 SPINT1 CHP1 EXD1 ENSG00000259463 ENSG00000259521
GH15F040981 0.8 Ensembl ENCODE 11.5 +54.9 54861 4.9 CTCF JUN CEBPG FOSL1 GATA3 GATA2 FOS NFE2L2 SMARCE1 BHLHE40 CHAC1 DLL4 NDUFAF1 SPINT1 INO80 IVD GC15M040995 LOC105370789
GH15F040972 0.8 ENCODE 11.4 +42.9 42865 0.2 GTF3C2 JUND ZFHX2 SP3 POLR3A USF2 FOS DNAJC17 ENSG00000259211 BAHD1 RPAP1 DLL4 NDUFAF1 BMF MAPKBP1 CHP1 EXD1
GH15F040973 0.2 ENCODE 11.4 +43.1 43105 0.2 SP3 POLR3A SP2 PRDM10 DLL4 MAPKBP1 CHP1 EXD1 LOC105370789 GC15M040995
- Elite enhancer/Elite enhancer-gene association Download Table
Download GeneHancer data dump

Enhancers around DLL4 on UCSC Golden Path with GeneCards custom track

Promoters for DLL4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001794253 467 1601 PKNOX1 DMAP1 ZNF48 ZNF2 GLIS2 ZNF263 SP3 REST MBD2 ZNF610
ENSR00001794252 -833 201 KLF1 ZIC2 ZNF366 SCRT2 IKZF1 GLIS1 KLF9 PRDM10 KLF7 ZBTB26
ENSR00000406733 1767 601 HDAC1 CBX3 ZNF76 KLF17 DMAP1 ZBTB40 ZNF2 RAD21 GLIS2 ETV6

Genomic Location for DLL4 Gene

Chromosome:
15
Start:
40,929,333 bp from pter
End:
40,939,072 bp from pter
Size:
9,740 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 StructureGene Density

RefSeq DNA sequence for DLL4 Gene

Proteins for DLL4 Gene

  • 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).

neXtProt entry for DLL4 Gene

Post-translational modifications for DLL4 Gene

  • Glycosylation at Asn 108, Asn 183, Asn 205, and Asn 393
  • Modification sites at PhosphoSitePlus

Other Protein References for DLL4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for DLL4 (DLL4)
  • Abcam antibodies for DLL4

No data available for DME Specific Peptides for DLL4 Gene

Domains & Families for DLL4 Gene

Suggested Antigen Peptide Sequences for DLL4 Gene

GenScript: Design optimal peptide antigens:

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.
  • Contains 1 DSL domain.
  • Contains 8 EGF-like domains.
genes like me logo Genes that share domains with DLL4: view

No data available for Gene Families for DLL4 Gene

Function for DLL4 Gene

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:

Gene Ontology (GO) - Molecular Function for DLL4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005112 Notch binding IEA,TAS --
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

Inhibitory RNA Products

Clone Products

Flow Cytometry 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
Jensen Localization Image for DLL4 Gene COMPARTMENTS Subcellular localization image for DLL4 gene
Compartment Confidence
plasma membrane 5
extracellular 3
cytoskeleton 1
lysosome 1
mitochondrion 1
nucleus 1
vacuole 1

Gene Ontology (GO) - Cellular Components for DLL4 Gene

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

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 from RNA polymerase II promoter ISS --
GO:0001525 angiogenesis IEA,ISS --
GO:0001569 branching involved in blood vessel morphogenesis IEA,ISS --
GO:0001974 blood vessel remodeling IEA,ISS --
GO:0003208 cardiac ventricle morphogenesis IEA,ISS --
genes like me logo Genes that share ontologies with DLL4: view

Drugs & Compounds for DLL4 Gene

(2) Drugs for DLL4 Gene - From: DGIdb

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
DEMCIZUMAB Pharma 0
REGN421 Pharma other, Inhibitor Other, Notch pathway inhibitors 0

(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

mRNA/cDNA for DLL4 Gene

Unigene Clusters for DLL4 Gene

Delta-like 4 (Drosophila):
Representative Sequences:

Inhibitory RNA Products

Clone Products

Flow Cytometry 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

mRNA expression in normal human tissues 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, PaxDb, 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.
genes like me logo Genes that share expression patterns with DLL4: view

Primer Products

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 34 35
  • 99.51 (n)
dog
(Canis familiaris)
Mammalia DLL4 34 35
  • 90.85 (n)
cow
(Bos Taurus)
Mammalia DLL4 34 35
  • 90.36 (n)
rat
(Rattus norvegicus)
Mammalia Dll4 34
  • 86.86 (n)
mouse
(Mus musculus)
Mammalia Dll4 34 16 35
  • 86.07 (n)
oppossum
(Monodelphis domestica)
Mammalia DLL4 35
  • 81 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia DLL4 35
  • 75 (a)
OneToOne
chicken
(Gallus gallus)
Aves DLL4 34 35
  • 71.44 (n)
lizard
(Anolis carolinensis)
Reptilia DLL4 35
  • 61 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia dll4 34
  • 64.87 (n)
zebrafish
(Danio rerio)
Actinopterygii dll4 34 35
  • 62.47 (n)
fruit fly
(Drosophila melanogaster)
Insecta Dl 36 35
  • 44 (a)
CG15388 36
  • 38 (a)
C901 36
  • 37 (a)
worm
(Caenorhabditis elegans)
Secernentea apx-1 36
  • 35 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.7799 35
  • 32 (a)
ManyToMany
-- 35
  • 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)

Paralogs for DLL4 Gene

Paralogs for DLL4 Gene

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

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

Variants for DLL4 Gene

Sequence variations from dbSNP and Humsavar for DLL4 Gene

SNP ID Clin Chr 15 pos Sequence Context AA Info Type
rs796065345 Adams-Oliver syndrome 6 (AOS6) [MIM:616589], Pathogenic 40,936,352(+) ACTTG(C/G)CATGA reference, missense
rs796065346 Adams-Oliver syndrome 6 (AOS6) [MIM:616589], Pathogenic 40,935,046(+) TGAAT(A/G)TCCCC reference, missense
rs796065347 Adams-Oliver syndrome 6 (AOS6) [MIM:616589], Pathogenic 40,935,045(+) GTGAA(C/T)GTCCC reference, missense
rs796065348 Adams-Oliver syndrome 6 (AOS6) [MIM:616589], Pathogenic 40,931,664(+) GCTCC(C/T)GCCTG reference, missense
rs796065349 Adams-Oliver syndrome 6 (AOS6) [MIM:616589], Pathogenic 40,932,396(+) GCACT(A/C)CCTGG reference, missense

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)

Relevant External Links for DLL4 Gene

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

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: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
adams-oliver syndrome 6
  • aos6
aplasia cutis congenita, nonsyndromic
  • acc
adams-oliver syndrome
  • adams oliver syndrome
oliver syndrome
  • postaxial polydactyly mental retardation
aplasia cutis congenita
  • acc
- 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.

Relevant External Links for DLL4

Atlas of Genetics and Cytogenetics in Oncology and Haematology:
DLL4
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 J.R. … Stark K.L. (Genes Dev. 2000) 2 3 4 22 64
  2. Heterozygous Loss-of-Function Mutations in DLL4 Cause Adams-Oliver Syndrome. (PMID: 26299364) Meester J.A. … Wuyts W. (Am. J. Hum. Genet. 2015) 3 4 64
  3. Integrin cytoplasmic domain-associated protein-1 attenuates sprouting angiogenesis. (PMID: 20616313) Brutsch R. … Fischer A. (Circ. Res. 2010) 3 4 64
  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 22 64
  5. Expression of Delta-like protein 4 in the human endometrium. (PMID: 17916635) Mazella J. … Tseng L. (Endocrinology 2008) 3 22 64

Products for DLL4 Gene

Sources for DLL4 Gene

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