DLL1

Chr 6AD

delta like canonical Notch ligand 1

Also known as: DELTA1, DL1, Delta, NEDBAS

NCBI Gene: 28514ENSG00000198719UniProt: O00548OMIM: 606582

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. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismADLOEUF 0.101 OMIM phenotype
Clinical Summary— DLL1
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Gene-Disease Validity (ClinGen)
neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
65 unique Pathogenic / Likely Pathogenic· 317 VUS of 706 total submissions
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Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — DLL1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.10LOEUF
pLI 1.000
Z-score 5.20
OE 0.00 (0.00–0.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
1.82Z-score
OE missense 0.76 (0.69–0.83)
335 obs / 442.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.10)
0≤0.351.4
Missense OE?0.76 (0.69–0.83)
0≤0.61.4
Synonymous OE?1.23
0≤1.21.6
LoF obs/exp: 0 / 31.5Missense obs/exp: 335 / 442.5Syn Z: -2.49
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateDLL1-related neurodevelopmental disorder with nonspecific brain abnormalities, with or without seizuresLOFAD

This gene — mechanism propensity

DN
0.3693th %ile
GOF
0.5268th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 91% of P/LP variants are LoF · LOEUF 0.10 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFHaploinsufficiency of the Notch Ligand DLL1 Causes Variable Neurodevelopmental Disorders.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

  1. 1.PMID 31353024 ↗

ClinVar Variant Classifications

706 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic25
VUS317
Likely Benign242
Benign36
Conflicting33
40
Pathogenic
25
Likely Pathogenic
317
VUS
242
Likely Benign
36
Benign
33
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
38
0
2
0
40
Likely Pathogenic
21
4
0
0
25
VUS
6
291
16
4
317
Likely Benign
0
20
68
154
242
Benign
0
6
22
8
36
Conflicting
—33
Total65321108166693

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

87 pathogenic / likely-pathogenic (of 96) ClinVar copy-number / structural variants overlap DLL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

DLL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
CAR-T Cell Therapy

Dual Target CAR-T Cell Treatment for Refractory Systemic Lupus Erythematosus (SLE) Patients

RECRUITING
NCT05858684Phase EARLY_PHASE1RenJi HospitalStarted 2023-05-11
GC012F injection
Liver Cancer

Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Patients With Pediatric Solid Tumors (GAP)

ACTIVE NOT RECRUITING
NCT02932956Phase PHASE1Baylor College of MedicineStarted 2018-12-17
GAP T cellsCytoxanFludara
Liver Cell CarcinomaSolid TumorWilms Tumor

Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in Autologous T Cells for Solid Tumors

ACTIVE NOT RECRUITING
NCT05103631Phase PHASE1Baylor College of MedicineStarted 2021-06-17
CATCH T cells
T-Cell Acute Lymphoblastic Leukemia/Lymphoma

Anti-CD7 CAR-T Cells in Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia or Lymphoma

RECRUITING
NCT06934382Phase PHASE1Stephan Grupp MD PhDStarted 2025-04-29
Allogeneic anti-CD7 CAR-T cells (BEAM-201)
Hodgkin LymphomaNon-Hodgkin LymphomaHodgkin Disease

Administration of TAA-Specific CTLs; Hodgkin or Non-Hodgkin Lymphoma; TACTAL

ACTIVE NOT RECRUITING
NCT01333046Phase PHASE1Baylor College of MedicineStarted 2012-01
Antigen-Escalation StageDose-Escalation Stageazacytidine and multiTAA T cells Stage
Liver CancerRhabdomyosarcomaMalignant Rhabdoid Tumor

Interleukin-15 Armored Glypican 3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors

ACTIVE NOT RECRUITING
NCT04377932Phase PHASE1Baylor College of MedicineStarted 2021-08-08
AGAR T cells
LeukemiaMyelodysplastic SyndromesLymphoma

Study of Gene Modified Donor T Cell Infusion in Patients With Recurrent Disease After Allogeneic Transplant

ACTIVE NOT RECRUITING
NCT02477878Phase PHASE1Bellicum PharmaceuticalsStarted 2016-07
BPX-501Rimiducid
T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma

CD7-CAR-T Cells in Pediatric Relapsed/Refractory CD7+ T-ALL/LL

RECRUITING
NCT06064903Phase PHASE1, PHASE2Bambino Gesù Hospital and Research InstituteStarted 2024-04-21
CD7-CART01
HepatoblastomaHepatocellular CarcinomaWilms Tumor

Immunotherapy For Adults With GPC3-Positive Solid Tumors Using IL-15 and IL-21 Armored GPC3-CAR T Cells

RECRUITING
NCT06198296Phase PHASE1Baylor College of MedicineStarted 2025-06-10
21.15.GPC3-CAR T cells
B-cell Acute Lymphoblastic Leukemia

Allogeneic Second-generation CD19-CAR T Cells for Pediatric Relapsed/Refractory B-ALL

RECRUITING
NCT06080191Phase PHASE1Bambino Gesù Hospital and Research InstituteStarted 2024-04-28
CD19-CAR_Lenti_ALLO
Brain TumorCancer

A Phase I/II Study of Zotiraciclib for Recurrent Malignant Gliomas With Isocitrate Dehydrogenase 1 or 2 (IDH1 or IDH2) Mutations

RECRUITING
NCT05588141Phase PHASE1, PHASE2National Cancer Institute (NCI)Started 2023-05-16
Zotiraciclib
LymphomaLymphoma, B-CellImmune System Diseases

Anti-CD19 CAR-T Cells With Inducible Caspase 9 Safety Switch for B-cell Lymphoma

ACTIVE NOT RECRUITING
NCT03696784Phase PHASE1UNC Lineberger Comprehensive Cancer CenterStarted 2019-03-12
iC9-CAR19 T cellsBendamustineFludarabine

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients