ROR1

ROR1
Identifiers
Aliases	ROR1, NTRKR1, dJ537F10.1, receptor tyrosine kinase-like orphan receptor 1, receptor tyrosine kinase like orphan receptor 1
External IDs	OMIM: 602336; MGI: 1347520; HomoloGene: 3675; GeneCards: ROR1; OMA:ROR1 - orthologs
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p31.3 Start 63,774,017 bp[1] End 64,181,498 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4 C6|4 45.71 cM Start 99,952,988 bp[2] End 100,301,962 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in germinal epithelium popliteal artery tibial arteries islet of Langerhans right coronary artery lower lobe of lung saphenous vein Descending thoracic aorta sural nerve buccal mucosa cell Top expressed in epithelium of lens gastrula umbilical cord abdominal wall decidua medullary collecting duct atrioventricular valve efferent ductule vestibular sensory epithelium maxillary prominence More reference expression data BioGPS n/a
Gene ontology Molecular function transmembrane receptor protein tyrosine kinase activity nucleotide binding protein binding protein kinase activity Wnt-protein binding kinase activity ATP binding transferase activity coreceptor activity involved in Wnt signaling pathway, planar cell polarity pathway Wnt-activated receptor activity receptor tyrosine kinase transmembrane signaling receptor activity Cellular component receptor complex integral component of plasma membrane integral component of membrane membrane stress fiber cytoplasm cell surface plasma membrane axon terminus axon cell projection Biological process phosphorylation protein phosphorylation Wnt signaling pathway transmembrane receptor protein tyrosine kinase signaling pathway Wnt signaling pathway, planar cell polarity pathway peptidyl-tyrosine phosphorylation astrocyte development hearing positive regulation of I-kappaB kinase/NF-kappaB signaling inner ear development positive regulation of NF-kappaB transcription factor activity negative regulation of signal transduction cell differentiation negative regulation of apoptotic process positive regulation of ERK1 and ERK2 cascade anatomical structure development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4919 26563 Ensembl ENSG00000185483 ENSMUSG00000035305 UniProt Q01973 Q9Z139 RefSeq (mRNA) NM_001083592 NM_005012 NM_013845 NM_001312690 RefSeq (protein) NP_001077061 NP_005003 NP_001299619 NP_038873 Location (UCSC) Chr 1: 63.77 – 64.18 Mb Chr 4: 99.95 – 100.3 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Tyrosine-protein kinase transmembrane receptor ROR1, also known as neurotrophic tyrosine kinase, receptor-related 1 (NTRKR1), is an enzyme that in humans is encoded by the ROR1 gene.^[5][6][7] ROR1 is a member of the receptor tyrosine kinase-like orphan receptor (ROR) family.

Function

The protein encoded by this gene is a receptor tyrosine kinase that modulates neurite growth in the central nervous system. It is a type I membrane protein and belongs to the ROR subfamily of cell surface receptors.^[5] ROR1 is currently under investigation for its role in the metastasis of cancer cells.^[8]

ROR1 has recently been shown to be expressed on ovarian cancer stem cell, on which it seems to play a functional role in promoting migration/invasion or spheroid formation in vitro and tumor engraftment in immune-deficient mice. Treatment with a humanized mAb specific for ROR1 (UC-961) could inhibit the capacity of ovarian cancer cells to migrate, form spheroids, or engraft immune-deficient mice. Moreover, such treatment inhibited the growth of tumor xenografts, which in turn had a reduced capacity to engraft immune-deficient mice and were relatively depleted of cells with features of CSC, suggesting that treatment with UC-961 could impair CSC renewal. Collectively, these studies indicate that ovarian CSCs express ROR1, which may be targeted for anti-CSC therapy.^[9]

Zilovertamab vedotin (ZV), an antibody–drug conjugate comprising a monoclonal antibody recognizing extracellular ROR1, a cleavable linker and monomethyl auristatin E has entered clinical trials for the treatment of lymphoid malignancies.^[10]

References

1. GRCh38: Ensembl release 89: ENSG00000185483 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000035305 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: receptor tyrosine kinase-like orphan receptor 1".
6. Masiakowski P, Carroll RD (Dec 1992). "A novel family of cell surface receptors with tyrosine kinase-like domain". The Journal of Biological Chemistry. 267 (36): 26181–90. doi:10.1016/S0021-9258(18)35733-8. PMID 1334494.
7. Reddy UR, Phatak S, Pleasure D (Oct 1996). "Human neural tissues express a truncated Ror1 receptor tyrosine kinase, lacking both extracellular and transmembrane domains". Oncogene. 13 (7): 1555–9. PMID 8875995.
8. Cui B, Zhang S, Chen L, Yu J, Widhopf GF, Fecteau JF, Rassenti LZ, Kipps TJ (June 2013). "Targeting ROR1 inhibits epithelial-mesenchymal transition and metastasis". Cancer Research. 73 (12): 3649–60. doi:10.1158/0008-5472.CAN-12-3832. PMC 3832210. PMID 23771907.
   • Lay summary in: Grush L (October 23, 2015). "Stopping cancer's spread: New protein found to control deadly cancer metastasis". Fox News.
9. Zhang S, Cui B, Lai H, Liu G, Ghia EM, Widhopf GF, Zhang Z, Wu CC, Chen L, Wu R, Schwab R, Carson DA, Kipps TJ (Dec 2014). "Ovarian cancer stem cells express ROR1, which can be targeted for anti-cancer-stem-cell therapy". Proceedings of the National Academy of Sciences of the United States of America. 111 (48): 17266–71. Bibcode:2014PNAS..11117266Z. doi:10.1073/pnas.1419599111. PMC 4260559. PMID 25411317.
10. Wang M, et al. (2022). "Zilovertamab vedotin targeting of ROR1 as therapy for lymphoid cancers" (PDF). NEJM Evidence. 1 (1): EVIDoa2100001. doi:10.1056/EVIDoa2100001. PMID 38319241. S2CID 245430438.

Further reading

• Reddy UR, Phatak S, Allen C, Nycum LM, Sulman EP, White PS, Biegel JA (Apr 1997). "Localization of the human Ror1 gene (NTRKR1) to chromosome 1p31-p32 by fluorescence in situ hybridization and somatic cell hybrid analysis". Genomics. 41 (2): 283–5. doi:10.1006/geno.1997.4653. PMID 9143508.
• Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR (2010). "Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score". Molecular Medicine. 16 (7–8): 247–53. doi:10.2119/molmed.2009.00159. PMC 2896464. PMID 20379614.
• Nomi M, Oishi I, Kani S, Suzuki H, Matsuda T, Yoda A, Kitamura M, Itoh K, Takeuchi S, Takeda K, Akira S, Ikeya M, Takada S, Minami Y (Dec 2001). "Loss of mRor1 enhances the heart and skeletal abnormalities in mRor2-deficient mice: redundant and pleiotropic functions of mRor1 and mRor2 receptor tyrosine kinases". Molecular and Cellular Biology. 21 (24): 8329–35. doi:10.1128/MCB.21.24.8329-8335.2001. PMC 99997. PMID 11713269.
• Baskar S, Kwong KY, Hofer T, Levy JM, Kennedy MG, Lee E, Staudt LM, Wilson WH, Wiestner A, Rader C (Jan 2008). "Unique cell surface expression of receptor tyrosine kinase ROR1 in human B-cell chronic lymphocytic leukemia". Clinical Cancer Research. 14 (2): 396–404. doi:10.1158/1078-0432.CCR-07-1823. PMID 18223214.
• Shabani M, Asgarian-Omran H, Omran HA, Jeddi-Tehrani M, Vossough P, Faranoush M, Sharifian RA, Toughe GR, Kordmahin M, Khoshnoodi J, Roohi A, Tavoosi N, Mellstedt H, Rabbani H, Shokri F (2007). "Overexpression of orphan receptor tyrosine kinase Ror1 as a putative tumor-associated antigen in Iranian patients with acute lymphoblastic leukemia". Tumour Biology. 28 (6): 318–26. doi:10.1159/000121405. PMID 18354269. S2CID 82261.
• Daneshmanesh AH, Mikaelsson E, Jeddi-Tehrani M, Bayat AA, Ghods R, Ostadkarampour M, Akhondi M, Lagercrantz S, Larsson C, Osterborg A, Shokri F, Mellstedt H, Rabbani H (Sep 2008). "Ror1, a cell surface receptor tyrosine kinase is expressed in chronic lymphocytic leukemia and may serve as a putative target for therapy". International Journal of Cancer. 123 (5): 1190–5. doi:10.1002/ijc.23587. PMID 18546292.
• Smith EN, Bloss CS, Badner JA, Barrett T, Belmonte PL, Berrettini W, Byerley W, Coryell W, Craig D, Edenberg HJ, Eskin E, Foroud T, Gershon E, Greenwood TA, Hipolito M, Koller DL, Lawson WB, Liu C, Lohoff F, McInnis MG, McMahon FJ, Mirel DB, Murray SS, Nievergelt C, Nurnberger J, Nwulia EA, Paschall J, Potash JB, Rice J, Schulze TG, Scheftner W, Panganiban C, Zaitlen N, Zandi PP, Zöllner S, Schork NJ, Kelsoe JR (Aug 2009). "Genome-wide association study of bipolar disorder in European American and African American individuals". Molecular Psychiatry. 14 (8): 755–63. doi:10.1038/mp.2009.43. PMC 3035981. PMID 19488044.
• Paganoni S, Ferreira A (Jan 2005). "Neurite extension in central neurons: a novel role for the receptor tyrosine kinases Ror1 and Ror2". Journal of Cell Science. 118 (Pt 2): 433–46. doi:10.1242/jcs.01622. PMC 1351101. PMID 15654020.
• Shabani M, Asgarian-Omran H, Vossough P, Sharifian RA, Faranoush M, Ghragozlou S, Khoshnoodi J, Roohi A, Jeddi-Tehrani M, Mellstedt H, Rabbani H, Shokri F (Jul 2008). "Expression profile of orphan receptor tyrosine kinase (ROR1) and Wilms' tumor gene 1 (WT1) in different subsets of B-cell acute lymphoblastic leukemia". Leukemia & Lymphoma. 49 (7): 1360–7. doi:10.1080/10428190802124000. PMID 18604725. S2CID 22958582.
• Fukuda T, Chen L, Endo T, Tang L, Lu D, Castro JE, Widhopf GF, Rassenti LZ, Cantwell MJ, Prussak CE, Carson DA, Kipps TJ (Feb 2008). "Antisera induced by infusions of autologous Ad-CD154-leukemia B cells identify ROR1 as an oncofetal antigen and receptor for Wnt5a". Proceedings of the National Academy of Sciences of the United States of America. 105 (8): 3047–52. Bibcode:2008PNAS..105.3047F. doi:10.1073/pnas.0712148105. PMC 2268582. PMID 18287027.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.