From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
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
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 .