DLL1

Chr 6AD

delta like canonical Notch ligand 1

Also known as: DELTA1, DL1, Delta, NEDBAS

NCBI Gene: 28514 ENSG00000198719 UniProt: O00548 OMIM: 606582

This gene encodes a transmembrane ligand protein that binds to NOTCH receptors and regulates cell fate decisions during embryonic development, particularly in brain development where it controls neuronal differentiation and maintains neural stem cell quiescence. Mutations cause neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.095), reflecting its critical role in development.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizuresMIM #618709

Clinical highlights

Gene-disease validity (ClinGen)

neurodevelopmental disorder with nonspecific brain abnormalities and with or without seizures · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.10

LOEUF· LoF intol.

LOF

Mechanism· G2P

📖

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

DLL1 · protein map & ClinVar variants

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

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

📖

GeneReview available — DLL1

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

HR-positive, HER2-negative Breast CancerTNBC - Triple-Negative Breast CancerProstate Cancer

Gene-edited T Regulatory Cells (CRG-150) for the Treatment of Relapsed/Refractory Malignancies

NOT YET RECRUITING

NCT07730125Phase PHASE1, PHASE2CoRegen, Inc.Started 2026-11

CRG-150

Anatomic Stage III Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8Metastatic Triple-Negative Breast Carcinoma

Testing the Addition of Copanlisib to Eribulin in Metastatic Triple Negative Breast Cancer

ACTIVE NOT RECRUITING

NCT04345913Phase PHASE1, PHASE2National Cancer Institute (NCI)Started 2021-03-01

Biopsy ProcedureBiospecimen CollectionComputed Tomography

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

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

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

EGFR Gene MutationGlioblastomaMGMT-Unmethylated Glioblastoma

Anti-EGFRvIII synNotch Receptor Induced Anti-EphA2/IL-13Ralpha2 CAR (E-SYNC) T Cells

RECRUITING

NCT06186401Phase PHASE1Hideho Okada, MD, PhDStarted 2024-04-30

E-SYNC T CellsCyclophosphamide (non-investigational)Fludarabine (non-investigational)

Relapsed/Refractory Small Cell Lung Cancer

This Study is an Open-lable, Early Study to Evaluate the Safety, Feasibility, Cytokinetics, and Preliminary Efficacy of GC511B in DLL3+ Relapsed/Refractory Small Cell Lung Cancer.

RECRUITING

NCT07249879Phase PHASE1Cancer Institute and Hospital, Chinese Academy of Medical SciencesStarted 2026-03-03

GC511B CAR-T Cell Injection

Acute Myeloid Leukemia

Chimeric Antigen Receptor T-cells for The Treatment of AML Expressing CLL-1 Antigen

ACTIVE NOT RECRUITING

NCT04219163Phase PHASE1Baylor College of MedicineStarted 2020-07-09

CLL-1.CAR T cells

Liver CancerRhabdomyosarcomaMalignant Rhabdoid Tumor

Interleukin-15 and -21 Armored Glypican-3-specific Chimeric Antigen Receptor Expressed in T Cells for Pediatric Solid Tumors

RECRUITING

NCT04715191Phase PHASE1Baylor College of MedicineStarted 2024-05-24