DLL3

Protein-coding gene in the species Homo sapiens

DLL3

Identifiers

Aliases

DLL3, SCDO1, pu, pudgy, delta like canonical Notch ligand 3

External IDs

OMIM: 602768; MGI: 1096877; HomoloGene: 7291; GeneCards: DLL3; OMA:DLL3 - orthologs

Gene location (Human)

Chr.	Chromosome 19 (human)^[1]

Band	19q13.2	Start	39,498,895 bp^[1]
Band	19q13.2	End	39,508,481 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 7 (mouse)^[2]

Band	7 A3\|7 16.67 cM	Start	27,992,978 bp^[2]
Band	7 A3\|7 16.67 cM	End	28,001,663 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

ganglionic eminence

gonad

testicle

ventricular zone

nucleus accumbens

amygdala

anterior cingulate cortex

prefrontal cortex

hypothalamus

putamen

Top expressed in

medial ganglionic eminence

seminiferous tubule

tail of embryo

primitive streak

embryo

embryo

epiblast

spermatid

morula

pars intermedia

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	Notch binding calcium ion binding
Cellular component	integral component of membrane membrane plasma membrane
Biological process	Notch signaling pathway somitogenesis multicellular organism development negative regulation of neurogenesis cell differentiation compartment pattern specification paraxial mesoderm development tissue development skeletal system development
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


10683


13389

Ensembl


ENSG00000090932


ENSMUSG00000003436

UniProt


Q9NYJ7


O88516

RefSeq (mRNA)


NM_016941 NM_203486


NM_007866

RefSeq (protein)


NP_058637 NP_982353


NP_031892

Location (UCSC)

Chr 19: 39.5 – 39.51 Mb

Chr 7: 27.99 – 28 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Delta-like 3 (Drosophila), also known as DLL3, is a protein which in humans is encoded by the DLL3 gene.^[5] Two transcript variants encoding distinct isoforms have been identified for this gene.

Function

This gene encodes a member of the delta protein ligand family. This family functions as Notch ligands that are characterized by a DSL domain, EGF repeats, and a transmembrane domain.^[6] Expression of DLL3 is highest in fetal brain. It plays a key role in somitogenesis within the paraxial mesoderm.^[7]

Clinical significance

Mutations in this gene cause the autosomal recessive genetic disorder Jarcho-Levin syndrome.^[8] Expression of the gene occurs in Neuroendocrine tumors, which has been targeted as a potential pathway for treatment.^[9]

Experimental drugs targetting DLL3 have been investigated as a possible treatment for lung cancer including Tarlatamab and rovalpituzumab tesirine.^[10]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000090932 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000003436 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Turnpenny PD, Bulman MP, Frayling TM, Abu-Nasra TK, Garrett C, Hattersley AT, Ellard S (July 1999). "A gene for autosomal recessive spondylocostal dysostosis maps to 19q13.1-q13.3". Am. J. Hum. Genet. 65 (1): 175–82. doi:10.1086/302464. PMC 1378088. PMID 10364530.
^ "DLL3 delta like canonical Notch ligand 3 [ Homo sapiens (human) ]".
^ Chapman G, Sparrow DB, Kremmer E, Dunwoodie SL (March 2011). "Notch inhibition by the ligand Delta-Like 3 defines the mechanism of abnormal vertebral segmentation in spondylocostal dysostosis". Human Molecular Genetics. 20 (5): 438–41. doi:10.1093/hmg/ddq529. PMID 21147753.
^ Bulman MP, Kusumi K, Frayling TM, McKeown C, Garrett C, Lander ES, Krumlauf R, Hattersley AT, Ellard S, Turnpenny PD (April 2000). "Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis". Nat. Genet. 24 (4): 438–41. doi:10.1038/74307. PMID 10742114. S2CID 9284439.
^ Saunders LR, Bankovich AJ, Anderson WC, Aujay MA, Bheddah S, Black K, Desai R, Escarpe PA, Hampl J, Laysang A, Liu D, Lopez-Molina J, Milton M, Park A, Pysz MA, Shao H, Slingerland B, Torgov M, Williams SA, Foord O, Howard P, Jassem J, Badzio A, Czapiewski P, Harpole DH, Dowlati A, Massion PP, Travis WD, Pietanza MC, Poirier JT, Rudin CM, Stull RA, Dylla SJ (August 2015). "A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo". Sci. Transl. Med. 7 (302): 302. doi:10.1126/scitranslmed.aac9459. PMC 4934375. PMID 26311731.
^ "Rovalpituzumab tesirine - Stemcentrx - AdisInsight".

External links

GeneReviews/NIH/NCBI/UW entry on Spondylocostal Dysostosis, Autosomal Recessive

Turnpenny PD, Bulman MP, Frayling TM, et al. (1999). "A gene for autosomal recessive spondylocostal dysostosis maps to 19q13.1-q13.3". Am. J. Hum. Genet. 65 (1): 175–82. doi:10.1086/302464. PMC 1378088. PMID 10364530.
Bulman MP, Kusumi K, Frayling TM, et al. (2000). "Mutations in the human delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis". Nat. Genet. 24 (4): 438–41. doi:10.1038/74307. PMID 10742114. S2CID 9284439.
Dunwoodie SL, Clements M, Sparrow DB, et al. (2002). "Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy gene Dll3 are associated with disruption of the segmentation clock within the presomitic mesoderm". Development. 129 (7): 1795–806. doi:10.1242/dev.129.7.1795. PMID 11923214. S2CID 7550276.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Turnpenny PD, Whittock N, Duncan J, et al. (2003). "Novel mutations in DLL3, a somitogenesis gene encoding a ligand for the Notch signalling pathway, cause a consistent pattern of abnormal vertebral segmentation in spondylocostal dysostosis". J. Med. Genet. 40 (5): 333–9. doi:10.1136/jmg.40.5.333. PMC 1735475. PMID 12746394.
Bonafé L, Giunta C, Gassner M, et al. (2004). "A cluster of autosomal recessive spondylocostal dysostosis caused by three newly identified DLL3 mutations segregating in a small village". Clin. Genet. 64 (1): 28–35. doi:10.1034/j.1399-0004.2003.00085.x. PMID 12791036. S2CID 45791073.
Whittock NV, Ellard S, Duncan J, et al. (2005). "Pseudodominant inheritance of spondylocostal dysostosis type 1 caused by two familial delta-like 3 mutations". Clin. Genet. 66 (1): 67–72. doi:10.1111/j.0009-9163.2004.00272.x. PMID 15200511. S2CID 46448881.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Maisenbacher MK, Han JS, O'brien ML, et al. (2005). "Molecular analysis of congenital scoliosis: a candidate gene approach". Hum. Genet. 116 (5): 416–9. doi:10.1007/s00439-005-1253-8. PMID 15717203. S2CID 21481013.
Otsuki T, Ota T, Nishikawa T, et al. (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Res. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.