DLL3

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

DLL3
Identifiers
Aliases	DLL3, SCDO1, pu, pudgy, delta like canonical Notch ligand 3
External IDs	OMIM: 602768 MGI: 1096877 HomoloGene: 7291 GeneCards: DLL3
Gene location (Human) Chr. Chromosome 19 (human) Band 19q13.2 Start 39,498,895 bp End 39,508,481 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7 A3|7 16.67 cM Start 27,992,978 bp End 28,001,663 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence nucleus accumbens amygdala prefrontal cortex hypothalamus putamen caudate nucleus Brodmann area 9 pancreatic ductal cell oocyte Top expressed in medial ganglionic eminence seminiferous tubule primitive streak spermatid morula pars intermedia spermatocyte organ of Corti mesoderm lens 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
Wikidata
View/Edit Human View/Edit Mouse

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. Expression of DLL3 is highest in fetal brain. It plays a key role in somitogenesis within the paraxial mesoderm.

Clinical significance

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

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

External links

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

Further reading

• 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.