DLL1

Summary

DLL1 (delta like canonical Notch ligand 1, HGNC:2908) is a protein-coding gene on chromosome 6q27, encoding Delta-like protein 1 (O00548). Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner. It is haploinsufficient (ClinGen: sufficient evidence).

DLL1 is a human homolog of the Notch Delta ligand and is a member of the delta/serrate/jagged family. It plays a role in mediating cell fate decisions during hematopoiesis. It may play a role in cell-to-cell communication.

Source: NCBI Gene 28514 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 710 total — 45 pathogenic, 22 likely-pathogenic
• Phenotypes (HPO): 126
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005618

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2908
Approved symbol	DLL1
Name	delta like canonical Notch ligand 1
Location	6q27
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000198719
Ensembl biotype	protein_coding
OMIM	606582
Entrez	28514

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000366756, ENST00000630500, ENST00000876123, ENST00000876124, ENST00000876125, ENST00000876126, ENST00000876127, ENST00000876128, ENST00000915772, ENST00000915773, ENST00000915774, ENST00000966432, ENST00000966433

RefSeq mRNA: 1 — MANE Select: NM_005618 NM_005618

CCDS: CCDS5313

Canonical transcript exons

ENST00000366756 — 11 exons

Exon	Start	End
ENSE00000766116	170282988	170283105
ENSE00000766117	170283231	170284029
ENSE00000766118	170284919	170285135
ENSE00000766119	170285254	170285423
ENSE00000766120	170285569	170285699
ENSE00000766121	170286238	170286298
ENSE00000766122	170288239	170288496
ENSE00000766123	170288729	170288789
ENSE00000766124	170289512	170289808
ENSE00001442547	170282206	170282879
ENSE00001836483	170290086	170291078

Expression profiles

Bgee: expression breadth ubiquitous, 132 present calls, max score 91.76.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9635 / max 21.1733, expressed in 450 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
76820	0.6668	357
76822	0.1715	88
76819	0.1251	48

Top tissues by expression

133 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	91.76	gold quality
ventricular zone	UBERON:0003053	85.87	gold quality
skin of abdomen	UBERON:0001416	85.74	gold quality
skin of leg	UBERON:0001511	85.63	gold quality
zone of skin	UBERON:0000014	85.52	gold quality
prostate gland	UBERON:0002367	85.24	gold quality
apex of heart	UBERON:0002098	84.69	gold quality
esophagus mucosa	UBERON:0002469	84.40	gold quality
vagina	UBERON:0000996	84.33	gold quality
lower esophagus mucosa	UBERON:0035834	84.31	gold quality
omental fat pad	UBERON:0010414	83.92	gold quality
right atrium auricular region	UBERON:0006631	83.12	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.97	gold quality
minor salivary gland	UBERON:0001830	82.74	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.66	gold quality
ganglionic eminence	UBERON:0004023	82.53	gold quality
mucosa of transverse colon	UBERON:0004991	82.52	gold quality
ectocervix	UBERON:0012249	82.16	gold quality
adipose tissue	UBERON:0001013	82.12	gold quality
small intestine	UBERON:0002108	81.94	gold quality
endocervix	UBERON:0000458	81.86	gold quality
saliva-secreting gland	UBERON:0001044	81.82	gold quality
transverse colon	UBERON:0001157	81.82	gold quality
subcutaneous adipose tissue	UBERON:0002190	80.81	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.79	gold quality
body of pancreas	UBERON:0001150	80.46	gold quality
thoracic mammary gland	UBERON:0005200	79.99	gold quality
heart left ventricle	UBERON:0002084	79.86	gold quality
esophagus	UBERON:0001043	79.65	gold quality
uterine cervix	UBERON:0000002	79.60	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	672.29
E-MTAB-6911	yes	452.42
E-MTAB-9906	yes	393.28
E-MTAB-8894	yes	220.55
E-GEOD-135922	yes	128.74
E-ANND-3	yes	4.68

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
NODAL	Activation

Upstream regulators (CollecTRI, top): ASCL1, CD46, CDX1, CTNNB1, CUX2, FOXC1, FOXC2, FOXN1, GATA4, HES1, LEF1, MECP2, MESP2, MYOD1, NEUROD1, NEUROG1, NEUROG2, NOTCH1, POU3F2, RBPJ, SOX4, STAT5A, TBX18, TBX6

miRNA regulators (miRDB)

128 targeting DLL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Delta-1 can enhance myeloid and lymphoid marrow-repopulating ability and promote the generation of thymus-repopulating T cell precursors. (PMID:12393852)
• suppresses the self-renewal capacity and long-term growth of two myeloblastic leukemia cell lines (PMID:12684674)
• Dll1 is a substrate for regulated intramembrane proteolysis, and its intracellular region possibly fulfills a specific function in the nucleus (PMID:12794186)
• Delta and Jagged undergo ADAM-mediated ectodomain processing followed by PS-mediated intramembrane proteolysis to release signaling fragments (PMID:12826675)
• induces a NIH 3T3 cell tranformed phenotype mediated by FGF signaling. (PMID:14769803)
• Delta-1 and Jagged-1 have roles in growth suppression in two myeloid leukemia cell lines (PMID:15254769)
• Notch ligand, Delta-1, reduced the TNF-alpha-induced growth suppression and apoptosis in U937 cells. (PMID:15492857)
• Down-regulation of Notch-1, Delta-like-1, or Jagged-1 by RNA interference induces apoptosis and inhibits proliferation in multiple glioma cell lines. (PMID:15781650)
• Density of the Notch ligand Delta1 determines generation of B and T cell precursors from hematopoietic stem cells. (PMID:15851488)
• When a dominant-negative form of kuzmanian in transgenic mice impairs Notch signaling in receiving T-cells, increasing Delta-1 on sending cells overcomes this defect. (PMID:15905513)
• Dll1 is presented on the surface of AJs formed at the apical termini of processes through interaction with MAGI1 to activate Notch on neighboring cells in the developing central nervous system (PMID:15908431)
• culture with increased amounts of Delta1(ext-IgG) induced apoptosis of CD34+ precursors resulting in decreased cell numbers, without affecting generation of CD7+ cells (PMID:15976178)
• The expression of the intracellular domain of Delta1 results in a non-proliferating senescent-like cell phenotype which is dependent on the expression of the cell cycle inhibitor, p21. (PMID:16225865)
• Data describe the immunohistochemical staining pattern of four Notch receptors (Notch1-4) and their ligands (Delta1 and Jagged1) in synovial tissues obtained from rheumatoid arthritis patients. (PMID:16307184)
• DL1-induced activation of the Notch1 pathway controls the lineage commitment of early thymic precursors by altering the levels between Spi-B and GATA-3. (PMID:16317090)
• Dll1 was expressed in arterial endothelial cells, not venous Ecs or capillaries. Notch signaling by induction of Dll1 is necessary & sufficient to regulate ephrin-B2 expression & EphB2- & EphB4-dependent branching morphogenesis in arterial EC. (PMID:17234965)
• with supervised resistance exercise training, expression of Notch1 and Hes6 genes were increased and Delta-like 1 and Numb expression were decreased. (PMID:17301032)
• Tbx18 interacts with Gata4 and Nkx2-5 and competes Tbx5-mediated activation of the cardiac Natriuretic peptide precursor type a-promoter. Tbx18 down-regulates Tbx6-activated Delta-like 1 expression in the somitic mesoderm in vivo (PMID:17584735)
• Notch ligand Delta-1 enhances the sIL-6R-mediated effects of IL-6 on the generation of erythroid cells. (PMID:17939407)
• Report the antitumor effects of COX2 inhibitors may be associated with effects on the Delta1/Notch1 pathway in colon tumor cells. (PMID:18320325)
• The intracellular region of Notch ligands Dll1 and Dll3 regulates their trafficking and signaling activity (PMID:18676613)
• Delta1 and Jagged1 are expressed in human umbilical cord epithelial cells at the mRNA and protein level. (PMID:19150223)
• DLL1 was found downregulated in immune thrombocytopenic purpura. (PMID:19603167)
• Findings suggest a positive feedback loop between Notch1 and DLL1 in the U251MG glioma cell line. (PMID:19724883)
• these results suggest a link between Dll1 expression and human goblet cell differentiation that might be mediated by a function that is distinct from its role as a Notch receptor ligand. (PMID:20170633)
• revealed a striking difference between the responses of Notch to trans- and cis-Delta: whereas the response to trans-Delta is graded, the response to cis-Delta is sharp and occurs at a fixed threshold, independent of trans-Delta (PMID:20418862)
• Delta1 protein is involved in the cytodifferentiation of squamous odontogenic tumors of the mandible. (PMID:20554499)
• Relapse-free survival and overall survival showed a significantly shorter survival in acute myeloid leukemia patients with higher Notch1 expression, higher Jagged1 expression, or higher Delta1 expression. (PMID:20812035)
• findings implicate DLL1 in early patterning of the forebrain and identify NOTCH as a new signaling pathway involved in Holoprosencephaly. (PMID:21196490)
• In this study, Delta 1 ligand was detected in the lining epithelium of human periapical cysts with limited inflammation, showing Notch pathway activation in those cells. (PMID:21238798)
• we have investigated their influence on early human hematopoiesis and show that Jagged2 affects hematopoietic lineage decisions very similarly as Delta-like-1 and -4, but very different from Jagged1 (PMID:21372153)
• growth rate of Delta1-deficient dental pulp stem cells was significantly suppressed as compared with wild type cells (PMID:21392732)
• The stromal cell-mediated antiapoptotic effect on B- ALL cells is mediated by Notch-3 and -4 or Jagged-1/-2 and DLL-1 in a synergistic manner. (PMID:21602525)
• Notch1 and its ligand Delta-like 1(DLL1) are miR-449 bona fide targets (PMID:21602795)
• regulates Notch1 signaling through disruption of the Notch1-IC-RBP-Jk transcription activator complex (PMID:21643850)
• The receptors Notch2, -3, -4 and their ligands Jagged1, -2 and Delta1, -4 were detected at both the mRNA and protein level in early and late placenta (PMID:21726900)
• DLL1, which encodes Delta-like 1, the ligand for Notch3, is strongly implicated as the chromosome 6q27 Visceral leishmaniasis susceptibility gene. (PMID:21742847)
• as compared to MSC, OP9 cells were more efficient at inducing self-renewal and/or de novo generation of primitive (CD34(+) CD38(-) Lin(-)) cells, and suggest that such effects were due, at least in part, to the presence of Jagged-1 and DL1. (PMID:21911304)
• MiR-34a targeting of Notch ligand delta-like 1 impairs CD15+/CD133+ tumor-propagating cells and supports neural differentiation in medulloblastoma (PMID:21931765)
• An anti-delta1 Notch protein-blocking monoclonal antibody is able to prolong allograft survival in a fully histocompatibility-mismatched model of cardiac transplantation. (PMID:21949024)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	dla	ENSDARG00000010791
danio_rerio	dld	ENSDARG00000020219
mus_musculus	Dll1	ENSMUSG00000014773
rattus_norvegicus	Dll1	ENSRNOG00000059984
drosophila_melanogaster	Delta	FBGN0000463
drosophila_melanogaster	Ser	FBGN0004197
caenorhabditis_elegans	paml-2	WBGENE00009114
caenorhabditis_elegans	F55H12.3	WBGENE00010134
caenorhabditis_elegans		WBGENE00013498

Paralogs (5): JAG1 (ENSG00000101384), DLL4 (ENSG00000128917), JAG2 (ENSG00000184916), DNER (ENSG00000187957), NOTCH4 (ENSG00000204301)

Protein

Protein identifiers

Delta-like protein 1 — O00548 (reviewed: O00548)

Alternative names: Drosophila Delta homolog 1

All UniProt accessions (3): A0A0D9SF76, A0A384P5C6, O00548

UniProt curated annotations — full annotation on UniProt →

Function. Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner. Following transinteraction, ligand cells produce mechanical force that depends of a clathrin-mediated endocytosis, requiring ligand ubiquitination, EPN1 interaction, and actin polymerisation; these events promote Notch receptor extracellular domain (NECD) transendocytosis and triggers Notch signaling through induction of cleavage, hyperphosphorylation, and nuclear accumulation of the intracellular domain of Notch receptors (NICD). Is required for embryonic development and maintenance of adult stem cells in many different tissues and immune systeme; the DLL1-induced Notch signaling is mediated through an intercellular communication that regulates cell lineage, cell specification, cell patterning and morphogenesis through effects on differentiation and proliferation. Plays a role in brain development at different level, namely by regulating neuronal differentiation of neural precursor cells via cell-cell interaction, most likely through the lateral inhibitory system in an endogenous level dependent-manner. During neocortex development, Dll1-Notch signaling transmission is mediated by dynamic interactions between intermediate neurogenic progenitors and radial glia; the cell-cell interactions are mediated via dynamic and transient elongation processes, likely to reactivate/maintain Notch activity in neighboring progenitors, and coordinate progenitor cell division and differentiation across radial and zonal boundaries. During cerebellar development, regulates Bergmann glial monolayer formation and its morphological maturation through a Notch signaling pathway. At the retina and spinal cord level, regulates neurogenesis by preventing the premature differentiation of neural progenitors and also by maintaining progenitors in spinal cord through Notch signaling pathway. Also controls neurogenesis of the neural tube in a progenitor domain-specific fashion along the dorsoventral axis. Maintains quiescence of neural stem cells and plays a role as a fate determinant that segregates asymmetrically to one daughter cell during neural stem cells mitosis, resulting in neuronal differentiation in Dll1-inheriting cell. Plays a role in immune systeme development, namely the development of all T-cells and marginal zone (MZ) B-cells. Blocks the differentiation of progenitor cells into the B-cell lineage while promoting the emergence of a population of cells with the characteristics of a T-cell/NK-cell precursor. Also plays a role during muscle development. During early development, inhibits myoblasts differentiation from the medial dermomyotomal lip and later regulates progenitor cell differentiation. Directly modulates cell adhesion and basal lamina formation in satellite cells through Notch signaling. Maintains myogenic progenitors pool by suppressing differentiation through down-regulation of MYOD1 and is required for satellite cell homing and PAX7 expression. During craniofacial and trunk myogenesis suppresses differentiation of cranial mesoderm-derived and somite-derived muscle via MYOD1 regulation but in cranial mesoderm-derived progenitors, is neither required for satellite cell homing nor for PAX7 expression. Also plays a role during pancreatic cell development. During type B pancreatic cell development, may be involved in the initiation of proximodistal patterning in the early pancreatic epithelium. Stimulates multipotent pancreatic progenitor cells proliferation and pancreatic growth by maintaining HES1 expression and PTF1A protein levels. During fetal stages of development, is required to maintain arterial identity and the responsiveness of arterial endothelial cells for VEGFA through regulation of KDR activation and NRP1 expression. Controls sprouting angiogenesis and subsequent vertical branch formation through regulation on tip cell differentiation. Negatively regulates goblet cell differentiation in intestine and controls secretory fat commitment through lateral inhibition in small intestine. Plays a role during inner ear development; negatively regulates auditory hair cell differentiation. Plays a role during nephron development through Notch signaling pathway. Regulates growth, blood pressure and energy homeostasis.

Subunit / interactions. Homodimer. Interacts with TJP1. Interacts with MAGI1 (via PDZ domain); forms a complex with CTNNB1 and CDH2 and promotes recruitment to the adherens junction and stabilization on the cell surface. Interacts with PSEN1; undergoes a presenilin-dependent gamma-secretase cleavage that releases a Dll1-intracellular form. Interacts with MFAP5. Interacts with MIB1. Interacts with NEURL1B; leads to ubiquitination. Interacts with NEURL1. Interacts with SYNJ2BP; enhances DLL1 protein stability, and promotes Notch signaling in endothelial cells. Interacts with MAGI1, MAGI2, MAGI3 and MPDZ. Interacts (via ubiquitin) with EPN1 (via IUM domain); binding with NOTCH1 attached to neighboring cell, promotes ligand ubiquitination and EPN1 interaction, leading to NECD transendocytosis and Notch signaling. Interacts with NOTCH1. Interacts with NOTCH2NLB; leading to promote Notch signaling pathway in a cell-autonomous manner through inhibition of cis DLL1-NOTCH2 interactions.

Subcellular location. Apical cell membrane. Cell junction. Adherens junction. Membrane raft.

Tissue specificity. Expressed in heart and pancreas, with lower expression in brain and muscle and almost no expression in placenta, lung, liver and kidney.

Post-translational modifications. Ubiquitinated by MIB (MIB1 or MIB2), leading to its endocytosis and subsequent degradation. Ubiquitinated; promotes recycling back to the plasma membrane and confers a strong affinity for NOTCH1. Multi-ubiquitination of Lys-613 by MIB1 promotes both cis and trans-interaction with NOTCH1, as well as activation of Notch signaling. Ubiquitinated by NEURL1B. Phosphorylated in a membrane association-dependent manner. Phosphorylation at Ser-697 requires the presence of Ser-694, whereas phosphorylation at Ser-694 occurs independently of the other site. Phosphorylation is required for full ligand activity in vitro and affects surface presentation, ectodomain shedding, and endocytosis. O-fucosylated. Can be elongated to a disaccharide by MFNG.

Disease relevance. Neurodevelopmental disorder with non-specific brain abnormalities and with or without seizures (NEDBAS) [MIM:618709] An autosomal dominant disorder characterized by developmental delay, intellectual disability, seizures, autism spectrum disorder, behavioral abnormalities, and variable non-specific brain malformations. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
O00548-1	1	yes
O00548-2	2

RefSeq proteins (1): NP_005609* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001774	DSL	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR011651	Notch_ligand_N	Domain
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR051022

Pfam: PF00008, PF01414, PF07657, PF21700

UniProt features (97 total): strand 33, disulfide bond 27, domain 9, sequence variant 7, sequence conflict 3, region of interest 2, modified residue 2, topological domain 2, splice variant 2, helix 2, turn 2, signal peptide 1, chain 1, compositionally biased region 1, glycosylation site 1, transmembrane region 1, cross-link 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4XBM	X-RAY DIFFRACTION	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00548-F1	75.24	0.39

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 694, 697, 613

Disulfide bonds (27): 179–188, 192–204, 212–221, 226–237, 230–243, 245–254, 257–268, 263–274, 276–285, 292–304, 298–314, 316–325, 332–343, 337–352, 354–363, 370–381, 375–391, 393–402, 409–420, 414–429 …

Glycosylation sites (1): 477

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-2122948	Activated NOTCH1 Transmits Signal to the Nucleus
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2660826	Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant
R-HSA-2691232	Constitutive Signaling by NOTCH1 HD Domain Mutants
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2979096	NOTCH2 Activation and Transmission of Signal to the Nucleus
R-HSA-9013507	NOTCH3 Activation and Transmission of Signal to the Nucleus
R-HSA-9022702	MECP2 regulates transcription of neuronal ligands
R-HSA-9725554	Differentiation of Keratinocytes in Interfollicular Epidermis in Mammalian Skin
R-HSA-9793380	Formation of paraxial mesoderm
R-HSA-9824272	Somitogenesis
R-HSA-9831926	Nephron development

MSigDB gene sets: 704 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_HINDBRAIN_DEVELOPMENT, REACTOME_SIGNALING_BY_NOTCH, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_REGULATION_OF_SKELETAL_MUSCLE_TISSUE_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_AXIS_SPECIFICATION, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, WWTAAGGC_UNKNOWN

GO Biological Process (69): cell fate determination (GO:0001709), somitogenesis (GO:0001756), somite specification (GO:0001757), heart looping (GO:0001947), inhibition of neuroepithelial cell differentiation (GO:0002085), marginal zone B cell differentiation (GO:0002315), type B pancreatic cell development (GO:0003323), Notch signaling pathway (GO:0007219), determination of left/right symmetry (GO:0007368), compartment pattern specification (GO:0007386), regulation of blood pressure (GO:0008217), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), proximal/distal pattern formation (GO:0009954), positive regulation of gene expression (GO:0010628), astrocyte development (GO:0014002), regulation of somitogenesis (GO:0014807), spinal cord development (GO:0021510), cerebellar molecular layer formation (GO:0021688), cerebellar Purkinje cell layer structural organization (GO:0021693), hemopoiesis (GO:0030097), myeloid cell differentiation (GO:0030099), cell differentiation (GO:0030154), regulation of cell adhesion (GO:0030155), negative regulation of epithelial cell differentiation (GO:0030857), regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030947), negative regulation of interleukin-10 production (GO:0032693), negative regulation of glial cell apoptotic process (GO:0034351), organ growth (GO:0035265), regulation of growth (GO:0040008), inner ear auditory receptor cell differentiation (GO:0042491), negative regulation of cell differentiation (GO:0045596), negative regulation of epidermal cell differentiation (GO:0045605), negative regulation of inner ear auditory receptor cell differentiation (GO:0045608), negative regulation of myeloid cell differentiation (GO:0045638), negative regulation of myoblast differentiation (GO:0045662), negative regulation of neuron differentiation (GO:0045665), negative regulation of Notch signaling pathway (GO:0045746), positive regulation of Notch signaling pathway (GO:0045747), positive regulation of endocytosis (GO:0045807)

GO Molecular Function (6): Notch binding (GO:0005112), calcium ion binding (GO:0005509), Tat protein binding (GO:0030957), receptor ligand activity (GO:0048018), scaffold protein binding (GO:0097110), protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), plasma membrane (GO:0005886), adherens junction (GO:0005912), apical plasma membrane (GO:0016324), cytoplasmic vesicle (GO:0031410), membrane raft (GO:0045121), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Signaling by NOTCH1	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant	1
Signaling by NOTCH1 HD Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
Signaling by NOTCH2	1
Signaling by NOTCH3	1
Transcriptional Regulation by MECP2	1
Developmental Cell Lineages of the Integumentary System	1
Gastrulation	1
Formation of paraxial mesoderm	1
Kidney development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anterior/posterior pattern specification	2
anatomical structure formation involved in morphogenesis	2
somitogenesis	2
regulation of anatomical structure morphogenesis	2
cell population proliferation	2
regulation of cell population proliferation	2
signaling receptor binding	2
cellular anatomical structure	2
cell fate commitment	1
cellular developmental process	1
segmentation	1
chordate embryonic development	1
somite development	1
segment specification	1
embryonic pattern specification	1
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
negative regulation of epithelial cell differentiation	1
regulation of embryonic development	1
regulation of timing of cell differentiation	1
neuroepithelial cell differentiation	1
mature B cell differentiation involved in immune response	1
epithelial cell development	1
type B pancreatic cell differentiation	1
cell surface receptor signaling pathway	1
determination of bilateral symmetry	1
left/right pattern formation	1
blood circulation	1
regulation of biological quality	1
positive regulation of cellular process	1
negative regulation of cellular process	1
regionalization	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
glial cell development	1
astrocyte differentiation	1
regulation of multicellular organismal process	1
central nervous system development	1
anatomical structure development	1

Protein interactions and networks

STRING

2994 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DLL1	NOTCH2	Q04721	991
DLL1	NOTCH3	Q9UM47	988
DLL1	NOTCH1	P46531	988
DLL1	NOTCH4	Q99466	987
DLL1	RBPJ	Q06330	898
DLL1	LFNG	Q8NES3	892
DLL1	SMAD2	Q15796	874
DLL1	HEY1	Q9Y5J3	857
DLL1	HES5	Q5TA89	853
DLL1	MESP2	Q0VG99	777
DLL1	ASCL1	P50553	776
DLL1	POU3F3	P20264	740
DLL1	MAML2	Q8IZL2	734
DLL1	MAML1	Q92585	730
DLL1	MAML3	Q96JK9	723

IntAct

123 interactions, top by confidence:

A	B	Type	Score
SYNJ2BP	DLL1	psi-mi:“MI:0915”(physical association)	0.610
DLL1	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.610
MAGI2	DLL1	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
SCRIB	DLL1	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	FRMPD2	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	APBA1	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	DLL1	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	AHNAK	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440
DLL1	ARHGAP21	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (30): MIB1 (Affinity Capture-Western), DLL1 (Affinity Capture-RNA), NOTCH2 (Affinity Capture-Western), DLL1 (Reconstituted Complex), DLL1 (Reconstituted Complex), NOTCH2 (Affinity Capture-Western), DLL1 (Affinity Capture-RNA), DLL1 (Affinity Capture-Western), DLL1 (Reconstituted Complex), KIF7 (Affinity Capture-MS), HEATR5A (Affinity Capture-MS), NCK1 (Affinity Capture-MS), THAP11 (Affinity Capture-MS), KIAA0195 (Affinity Capture-MS), GNPAT (Affinity Capture-MS)

ESM2 similar proteins: A0A096LNW5, B8JI71, D3ZHH1, G3I6Z6, O00548, O35516, O57409, P0DPK3, P0DPK4, P35442, P46531, P78504, P97677, Q01705, Q04721, Q05793, Q07008, Q08E66, Q2QI47, Q5G872, Q5ZQU0, Q61483, Q63722, Q66PY1, Q6DI48, Q6NZL8, Q70E20, Q7TQN3, Q7Z3S9, Q8IWY4, Q8IX30, Q8JZM4, Q8K3K1, Q8NFT8, Q8TER0, Q8TEU8, Q8UWJ4, Q8VHS2, Q90Y54, Q90Y57

Diamond homologs: A0A1F4, A2RUV0, A4FV93, A8X481, B2LW77, B8JI71, D3ZHH1, D3ZUK3, G5EFX6, O00548, O35161, O35474, O43854, O57409, O88278, P07898, P10040, P10041, P18168, P21783, P78504, P82279, P97607, P97677, Q14517, Q19319, Q20911, Q28670, Q2PZL6, Q5IJ48, Q5R7K9, Q5ZQU0, Q61483, Q63722, Q6DI48, Q6UY11, Q6V0I7, Q70E20, Q80YA8, Q8JZM4

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
LFNG	up-regulates	DLL1	binding
DLL1	up-regulates	NOTCH2	binding
DLL1	“up-regulates activity”	NOTCH1	binding
DLL1	“up-regulates activity”	PP2B	binding
MIB1	“up-regulates activity”	DLL1	ubiquitination
DLL1	“up-regulates activity”	NOTCH	binding
DLL1	up-regulates	NOTCH3	binding
“A4/b1 integrin”	“up-regulates quantity by expression”	DLL1
“A5/b1 integrin”	“up-regulates quantity by expression”	DLL1
MECP2	“down-regulates quantity by repression”	DLL1	“transcriptional regulation”
DLL1	up-regulates	NOTCH	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	51.0×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	48.5×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	48.5×	2e-06
Assembly and cell surface presentation of NMDA receptors	10	45.3×	2e-12
Dopamine Neurotransmitter Release Cycle	5	44.3×	2e-06
Long-term potentiation	5	42.5×	2e-06
Neurexins and neuroligins	10	35.2×	2e-11
Protein-protein interactions at synapses	6	28.5×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	71.7×	3e-14
receptor clustering	7	53.9×	9e-09
protein localization to synapse	5	47.3×	4e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	6	36.7×	1e-06
cell-cell adhesion	10	12.5×	8e-07
protein-containing complex assembly	8	11.2×	3e-05
regulation of small GTPase mediated signal transduction	5	8.9×	5e-03
chemical synaptic transmission	7	6.7×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

710 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	45
Likely pathogenic	22
Uncertain significance	318
Likely benign	224
Benign	37

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1075313	NM_005618.4(DLL1):c.1616del (p.Gln539fs)	Pathogenic
1305879	NM_005618.4(DLL1):c.2048+2T>C	Pathogenic
1319865	NM_005618.4(DLL1):c.461_462del (p.Thr154fs)	Pathogenic
1327458	NM_005618.4(DLL1):c.1250-1G>A	Pathogenic
1452346	NM_005618.4(DLL1):c.1647C>A (p.Cys549Ter)	Pathogenic
1527330	GRCh37/hg19 6q27(chr6:170262214-170919482)	Pathogenic
1676790	NM_005618.4(DLL1):c.168C>A (p.Cys56Ter)	Pathogenic
1700086	NM_005618.4(DLL1):c.386_387del (p.Thr129fs)	Pathogenic
1709800	NM_005618.4(DLL1):c.1253_1259del (p.Ala418fs)	Pathogenic
1802546	NM_005618.4(DLL1):c.1538dup (p.Pro514fs)	Pathogenic
1878702	NM_005618.4(DLL1):c.38C>A (p.Ser13Ter)	Pathogenic
2052172	NM_005618.4(DLL1):c.1033-22_1033-8del	Pathogenic
2108500	NM_005618.4(DLL1):c.237C>A (p.Tyr79Ter)	Pathogenic
2443996	NM_005618.4(DLL1):c.351+1G>T	Pathogenic
2579015	NM_005618.4(DLL1):c.1775del (p.Asn592fs)	Pathogenic
2583043	NM_005618.4(DLL1):c.577dup (p.Arg193fs)	Pathogenic
2627420	NM_005618.4(DLL1):c.162C>A (p.Cys54Ter)	Pathogenic
2685223	GRCh37/hg19 6q27(chr6:170441452-170808613)x1	Pathogenic
2685224	GRCh37/hg19 6q27(chr6:170466312-170919482)x1	Pathogenic
2720636	NM_005618.4(DLL1):c.1249+1del	Pathogenic
2748309	NM_005618.4(DLL1):c.1615C>T (p.Gln539Ter)	Pathogenic
2823823	NM_005618.4(DLL1):c.137_152dup (p.Pro52fs)	Pathogenic
3246192	NC_000006.11:g.(?170589990)(170599227_?)del	Pathogenic
3250636	NM_005618.4(DLL1):c.1762G>T (p.Glu588Ter)	Pathogenic
3254980	NM_005618.4(DLL1):c.1077C>G (p.Tyr359Ter)	Pathogenic
3359007	NM_005618.4(DLL1):c.552C>G (p.Tyr184Ter)	Pathogenic
3366304	NM_005618.4(DLL1):c.1480del (p.Ala494fs)	Pathogenic
3382651	NM_005618.4(DLL1):c.883del (p.His295fs)	Pathogenic
3383967	NM_005618.4(DLL1):c.181del (p.Arg61fs)	Pathogenic
3384100	NM_005618.4(DLL1):c.635_636delinsAA (p.Cys212Ter)	Pathogenic

SpliceAI

1424 predictions. Top by Δscore:

Variant	Effect	Δscore
6:170283009:AT:A	donor_gain	1.0000
6:170283101:CTCCA:C	acceptor_gain	1.0000
6:170283102:TCCA:T	acceptor_gain	1.0000
6:170283103:CCA:C	acceptor_gain	1.0000
6:170283103:CCAC:C	acceptor_gain	1.0000
6:170283104:CA:C	acceptor_gain	1.0000
6:170283104:CAC:C	acceptor_gain	1.0000
6:170283105:ACTAA:A	acceptor_loss	1.0000
6:170283106:C:CC	acceptor_gain	1.0000
6:170283106:CTAA:C	acceptor_loss	1.0000
6:170283226:CGCA:C	donor_loss	1.0000
6:170283228:CACCC:C	donor_loss	1.0000
6:170283229:ACCC:A	donor_gain	1.0000
6:170283229:ACCCC:A	donor_gain	1.0000
6:170283230:CCCC:C	donor_gain	1.0000
6:170283230:CCCCC:C	donor_gain	1.0000
6:170283232:C:CA	donor_gain	1.0000
6:170283262:C:CA	donor_gain	1.0000
6:170283263:C:A	donor_gain	1.0000
6:170283313:C:A	donor_gain	1.0000
6:170284028:ACC:A	acceptor_loss	1.0000
6:170284029:CCTG:C	acceptor_loss	1.0000
6:170284030:C:CC	acceptor_gain	1.0000
6:170284030:CTGGA:C	acceptor_loss	1.0000
6:170284031:T:G	acceptor_loss	1.0000
6:170286232:ACTT:A	donor_loss	1.0000
6:170286233:CTT:C	donor_loss	1.0000
6:170286236:A:AC	donor_gain	1.0000
6:170286237:C:CC	donor_gain	1.0000
6:170286237:CTT:C	donor_gain	1.0000

AlphaMissense

4757 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:170285375:C:G	C304S	1.000
6:170285376:A:T	C304S	1.000
6:170285411:C:G	C292S	1.000
6:170285412:A:T	C292S	1.000
6:170285576:G:C	C285W	1.000
6:170285577:C:G	C285S	1.000
6:170285577:C:T	C285Y	1.000
6:170285578:A:T	C285S	1.000
6:170285591:C:A	W280C	1.000
6:170285591:C:G	W280C	1.000
6:170285079:A:C	C363W	0.999
6:170285080:C:G	C363S	0.999
6:170285080:C:T	C363Y	0.999
6:170285081:A:T	C363S	0.999
6:170285089:C:A	G360V	0.999
6:170285090:C:A	G360C	0.999
6:170285311:G:C	C325W	0.999
6:170285312:C:T	C325Y	0.999
6:170285368:G:C	N306K	0.999
6:170285368:G:T	N306K	0.999
6:170285374:G:C	C304W	0.999
6:170285375:C:T	C304Y	0.999
6:170285376:A:G	C304R	0.999
6:170285393:C:G	C298S	0.999
6:170285393:C:T	C298Y	0.999
6:170285394:A:T	C298S	0.999
6:170285410:G:C	C292W	0.999
6:170285411:C:T	C292Y	0.999
6:170285412:A:G	C292R	0.999
6:170285420:A:G	L289P	0.999

dbSNP variants (sampled 300 via entrez): RS1000206263 (6:170285197 A>G), RS1000216858 (6:170284199 G>A), RS1000680227 (6:170290548 C>A,T), RS1000712488 (6:170284442 C>T), RS1000908070 (6:170286495 T>G), RS1001208540 (6:170284089 A>G), RS1001651771 (6:170289046 A>C,G), RS1002552627 (6:170284079 C>A,G,T), RS1002559714 (6:170287667 C>T), RS1002654500 (6:170287855 G>A), RS1003021001 (6:170283410 C>G,T), RS1003050657 (6:170287110 A>G), RS1003106840 (6:170292519 C>T), RS1003801134 (6:170291710 C>T), RS1003930176 (6:170287134 T>G)

Disease associations

OMIM: gene MIM:606582 | disease phenotypes: MIM:618709, MIM:236100, MIM:613658, MIM:618007

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures	Definitive	Autosomal dominant
autosomal dominant non-syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures	Definitive	AD

Mondo (6): neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures (MONDO:0032877), prostate cancer (MONDO:0008315), holoprosencephaly (MONDO:0016296), alobar holoprosencephaly (MONDO:0019757), Rajab interstitial lung disease with brain calcifications 1 (MONDO:0100215), autosomal dominant non-syndromic intellectual disability (MONDO:0015802)

Orphanet (4): Familial prostate cancer (Orphanet:1331), Holoprosencephaly (Orphanet:2162), Alobar holoprosencephaly (Orphanet:93925), Interstitial lung disease-brain calcification syndrome (Orphanet:178506)

HPO phenotypes

126 total (30 of 126 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000062	Ambiguous genitalia
HP:0000104	Renal agenesis
HP:0000119	Abnormality of the genitourinary system
HP:0000161	Median cleft upper lip
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000202	Orofacial cleft
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000322	Short philtrum
HP:0000407	Sensorineural hearing impairment
HP:0000446	Narrow nasal bridge
HP:0000453	Choanal atresia
HP:0000457	Depressed nasal ridge
HP:0000463	Anteverted nares
HP:0000478	Abnormality of the eye
HP:0000486	Strabismus
HP:0000601	Hypotelorism
HP:0000612	Iris coloboma
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000736	Short attention span
HP:0000737	Irritability
HP:0000739	Anxiety
HP:0000741	Apathy

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001255_3	Type 1 diabetes	8.000000e-09
GCST002666_4	Interferon alpha levels in systemic lupus erythematosus	2.000000e-07
GCST006412_62	Intraocular pressure	5.000000e-14
GCST008369_11	Plasma anti-thyroglobulin levels	6.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006517	interferon alpha measurement
EFO:0004695	intraocular pressure measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016142	Holoprosencephaly	C05.660.207.410; C10.500.034.875; C16.131.077.410; C16.131.260.380; C16.131.621.207.410; C16.131.666.034.875; C16.320.180.380
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, decreases expression	7
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Benzo(a)pyrene	increases expression, increases methylation, increases mutagenesis	3
Tetrachlorodibenzodioxin	affects expression, increases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Vorinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
Particulate Matter	affects cotreatment, increases expression, decreases expression, increases abundance	2
lly-283	increases expression	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
sodium arsenate	increases abundance, increases expression	1
N(4)-hydroxycytidine	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, decreases expression	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
MRK 003	increases expression	1
Temozolomide	increases expression	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 stromal cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B7X0	Abcam Raji DLL1 KO	Cancer cell line	Male
CVCL_B9XL	Abcam THP-1 DLL1 KO	Cancer cell line	Male
CVCL_C6ZG	Abcam PC-3 DLL1 KO	Cancer cell line	Male
CVCL_D8K5	Ubigene HCT 116 DLL1 KO	Cancer cell line	Male
CVCL_VR88	MS5-hDLL1	Stromal cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
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