NELL1 Gene and the Identified Functions of the NELL-1 Protein
- Nakamura Y.
- Hasebe A.
- Takahashi K.
- Iijima M.
- Yoshimoto N.
- Ting K.
- Niimi T.
- Li C.
- Zheng Z.
- Ha P.
- Chen X.
- Jiang W.
- Sun S.
- Chen F.
- Asatrian G.
- Berthiaume E.A.
- Kim J.K.
- Chen E.C.
- Pang S.
- Zhang X.
- Ting K.
- Soo C.
- Jin Z.
- Mori Y.
- Yang J.
- Sato F.
- Ito T.
- Cheng Y.
- Paun B.
- Hamilton J.P.
- Kan T.
- Olaru A.
- David S.
- Agarwal R.
- Abraham J.M.
- Beer D.
- Montgomery E.
- Meltzer S.J.
- Li C.
- Zheng Z.
- Ha P.
- Chen X.
- Jiang W.
- Sun S.
- Chen F.
- Asatrian G.
- Berthiaume E.A.
- Kim J.K.
- Chen E.C.
- Pang S.
- Zhang X.
- Ting K.
- Soo C.
Genome-Wide Association Study of NELL1
- Franke A.
- Hampe J.
- Rosenstiel P.
- Becker C.
- Wagner F.
- Häsler R.
- Little R.D.
- Huse K.
- Ruether A.
- Balschun T.
- Wittig M.
- ElSharawy A.
- Mayr G.
- Albrecht M.
- Prescott N.J.
- Onnie C.M.
- Fournier H.
- Keith T.
- Radelof U.
- Platzer M.
- Mathew C.G.
- Stoll M.
- Krawczak M.
- Nürnberg P.
- Schreiber S.
- Franke A.
- Hampe J.
- Rosenstiel P.
- Becker C.
- Wagner F.
- Häsler R.
- Little R.D.
- Huse K.
- Ruether A.
- Balschun T.
- Wittig M.
- ElSharawy A.
- Mayr G.
- Albrecht M.
- Prescott N.J.
- Onnie C.M.
- Fournier H.
- Keith T.
- Radelof U.
- Platzer M.
- Mathew C.G.
- Stoll M.
- Krawczak M.
- Nürnberg P.
- Schreiber S.
- Van Ingen G.
- Li J.
- Goedegebure A.
- Pandey R.
- Rose Li Y.
- March M.E.
- Jaddoe V.W.V.
- Bakay M.
- Mentch F.D.
- Thomas K.
- Wei Z.
- Chang X.
- Hain H.S.
- Uitterlinden A.G.
- Moll H.A.
- Van Duijn C.M.
- Rivadeneira F.
- Raat H.
- De Jong R.J.B.
- Sleiman P.M.
- Van Der Schroeff M.P.
- Hakonarson H.

Classification of disorders | Publication | Sample size | Ethnicity | Evidence of association | SNPs | Location on NELL1 |
---|---|---|---|---|---|---|
Metabolic disease | ||||||
Osteoporosis | Karasik et al (2010) 28 | – | – | Nominal | rs10766761 | Intron 12 |
ALL BMD loss | Inaba et al (2018) 29 | 393 | American | Suggestive | rs11025915 | Intron 12 |
TG metabolism | Del-Aguila et al (2014) 30 | 767 | American | Genome-wide | rs12279250; rs4319515 | Intron 16; intron16 |
TG metabolism | Rudkowska et al (2014) 22 | 141 | Canadian | Suggestive | rs752088 | Intron 2 |
TG metabolism | Aslibekyan et al (2013) 31
Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network. Nutr Metab Cardiovasc Dis. 2013; 23: 987-994 | 793 | American | Suggestive | 25 SNPs | – |
Neuropsychiatric and neurodegenerative disorder | ||||||
Autism | Connolly et al (2013) 32 | 2165 | American | Genome-wide | rs1429793 | Intron 5 |
Bipolar | Mathieu et al (2015) 33 | 291 | French | Suggestive | rs10766743 | Intron 5 |
MDD | Lin et al (2018) 34 | 455 | Taiwanese | Suggestive | rs2139423 | Intron 2 |
Multiple sclerosis | Tiwari et al (2015) 35
The CombiRx Investigator Group GWAS on relapse outcomes in CombiRx trial Poster presented at: 31st Congress of European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Barcelona, Spain, October 7-10. 2015 | 608 | Caucasian | Suggestive | rs7130553 | Intron 15 |
Inflammatory diseases | ||||||
IBD | Franke et al (2007) 23
Systematic association mapping identifies NELL1 as a novel IBD disease gene. PLoS One. 2007; 2: e691 | 792 | German | Suggestive | rs1793004; rs8176785; rs8176786 | Intron 1; exon 3; exon 10 |
Chronic periodontitis | Sanders et al (2017) 36
Chronic periodontitis genome-wide association study in the Hispanic community health study/study of Latinos. J Dent Res. 2017; 96: 64-72 | 10,935 | Hispanic | Suggestive | rs75715012 | Intergenic region |
Otitis media | van Ingen et al (2016) 27
Genome-wide association study for acute otitis media in children identifies FNDC1 as disease contributing gene. Nat Commun. 2016; 7: 1-7 | 8790 | American | Nominally | rs11026076 | Intron 15 |
Cancer | ||||||
NSCLC | Wu et al (2013) 37
Genome-wide association study of genetic predictors of overall survival for non-small cell lung cancer in never smokers. Cancer Res. 2013; 73: 4028-4038 | 620 | American | Suggestive | rs10766739 | Intron 4 |
Other disorders | ||||||
Cardiovascular mortality | Figarska (2014) 38 | 1546 | Caucasian | Suggestive | rs11026076 | Intron 15 |
QT prolongation | Seyerle et al (2018) 25 | 78,199 | European | Suggestive | rs12225793 | Intron 12 |
Ovarian aging | Voorhuis (2013) 39 | 791 | European | Suggestive | rs7939346; rs10833509 | Intron 14 |
Metabolic Diseases
- Li C.
- Zheng Z.
- Ha P.
- Chen X.
- Jiang W.
- Sun S.
- Chen F.
- Asatrian G.
- Berthiaume E.A.
- Kim J.K.
- Chen E.C.
- Pang S.
- Zhang X.
- Ting K.
- Soo C.
Osteoporosis
- Rivadeneira F.
- Styrkársdottir U.
- Estrada K.
- Halldórsson B.V.
- Hsu Y.-H.
- Richards J.B.
- Zillikens M.C.
- Kavvoura F.K.
- Amin N.
- Aulchenko Y.S.
- Cupples L.A.
- Deloukas P.
- Demissie S.
- Grundberg E.
- Hofman A.
- Kong A.
- Karasik D.
- van Meurs J.B.
- Oostra B.
- Pastinen T.
- Pols H.A.P.
- Sigurdsson G.
- Soranzo N.
- Thorleifsson G.
- Thorsteinsdottir U.
- Williams F.M.K.
- Wilson S.G.
- Zhou Y.
- Ralston S.H.
- van Duijn C.M.
- Spector T.
- Kiel D.P.
- Stefansson K.
- Ioannidis J.P.A.
- Uitterlinden A.G.
- Rivadeneira F.
- Styrkársdottir U.
- Estrada K.
- Halldórsson B.V.
- Hsu Y.-H.
- Richards J.B.
- Zillikens M.C.
- Kavvoura F.K.
- Amin N.
- Aulchenko Y.S.
- Cupples L.A.
- Deloukas P.
- Demissie S.
- Grundberg E.
- Hofman A.
- Kong A.
- Karasik D.
- van Meurs J.B.
- Oostra B.
- Pastinen T.
- Pols H.A.P.
- Sigurdsson G.
- Soranzo N.
- Thorleifsson G.
- Thorsteinsdottir U.
- Williams F.M.K.
- Wilson S.G.
- Zhou Y.
- Ralston S.H.
- van Duijn C.M.
- Spector T.
- Kiel D.P.
- Stefansson K.
- Ioannidis J.P.A.
- Uitterlinden A.G.
- Styrkarsdottir U.
- Halldorsson B.V.
- Gretarsdottir S.
- Gudbjartsson D.F.
- Walters G.B.
- Ingvarsson T.
- Jonsdottir T.
- Saemundsdottir J.
- Center J.R.
- Nguyen T.V.
- Bagger Y.
- Gulcher J.R.
- Eisman J.A.
- Christiansen C.
- Sigurdsson G.
- Kong A.
- Thorsteinsdottir U.
- Stefansson K.
- Rivadeneira F.
- Styrkársdottir U.
- Estrada K.
- Halldórsson B.V.
- Hsu Y.-H.
- Richards J.B.
- Zillikens M.C.
- Kavvoura F.K.
- Amin N.
- Aulchenko Y.S.
- Cupples L.A.
- Deloukas P.
- Demissie S.
- Grundberg E.
- Hofman A.
- Kong A.
- Karasik D.
- van Meurs J.B.
- Oostra B.
- Pastinen T.
- Pols H.A.P.
- Sigurdsson G.
- Soranzo N.
- Thorleifsson G.
- Thorsteinsdottir U.
- Williams F.M.K.
- Wilson S.G.
- Zhou Y.
- Ralston S.H.
- van Duijn C.M.
- Spector T.
- Kiel D.P.
- Stefansson K.
- Ioannidis J.P.A.
- Uitterlinden A.G.
- Styrkarsdottir U.
- Halldorsson B.V.
- Gretarsdottir S.
- Gudbjartsson D.F.
- Walters G.B.
- Ingvarsson T.
- Jonsdottir T.
- Saemundsdottir J.
- Center J.R.
- Nguyen T.V.
- Bagger Y.
- Gulcher J.R.
- Eisman J.A.
- Christiansen C.
- Sigurdsson G.
- Kong A.
- Thorsteinsdottir U.
- Stefansson K.
- Shen J.
- James A.W.
- Zhang X.
- Pang S.
- Zara J.N.
- Asatrian G.
- Chiang M.
- Lee M.
- Khadarian K.
- Nguyen A.
- Lee K.S.
- Siu R.K.
- Tetradis S.
- Ting K.
- Soo C.
- Shen J.
- James A.W.
- Zhang X.
- Pang S.
- Zara J.N.
- Asatrian G.
- Chiang M.
- Lee M.
- Khadarian K.
- Nguyen A.
- Lee K.S.
- Siu R.K.
- Tetradis S.
- Ting K.
- Soo C.
Triglyceride-Related Metabolic Diseases
- Aslibekyan S.
- An P.
- Frazier-Wood A.C.
- Kabagambe E.K.
- Irvin M.R.
- Straka R.J.
- Tiwari H.K.
- Tsai M.Y.
- Hopkins P.N.
- Borecki I.B.
- Ordovas J.M.
- Arnett D.K.
- Shen J.
- James A.W.
- Zhang X.
- Pang S.
- Zara J.N.
- Asatrian G.
- Chiang M.
- Lee M.
- Khadarian K.
- Nguyen A.
- Lee K.S.
- Siu R.K.
- Tetradis S.
- Ting K.
- Soo C.
Neuropsychiatric and Neurodegenerative Disorders
- Li C.
- Zheng Z.
- Ha P.
- Chen X.
- Jiang W.
- Sun S.
- Chen F.
- Asatrian G.
- Berthiaume E.A.
- Kim J.K.
- Chen E.C.
- Pang S.
- Zhang X.
- Ting K.
- Soo C.
Autism Spectrum Disorder
- Karayannis T.
- Au E.
- Patel J.C.
- Kruglikov I.
- Markx S.
- Delorme R.
- Héron D.
- Salomon D.
- Glessner J.
- Restituito S.
- Gordon A.
- Rodriguez-Murillo L.
- Roy N.C.
- Gogos J.A.
- Rudy B.
- Rice M.E.
- Karayiorgou M.
- Hakonarson H.
- Keren B.
- Huguet G.
- Bourgeron T.
- Hoeffer C.
- Tsien R.W.
- Peles E.
- Fishell G.
- Karayannis T.
- Au E.
- Patel J.C.
- Kruglikov I.
- Markx S.
- Delorme R.
- Héron D.
- Salomon D.
- Glessner J.
- Restituito S.
- Gordon A.
- Rodriguez-Murillo L.
- Roy N.C.
- Gogos J.A.
- Rudy B.
- Rice M.E.
- Karayiorgou M.
- Hakonarson H.
- Keren B.
- Huguet G.
- Bourgeron T.
- Hoeffer C.
- Tsien R.W.
- Peles E.
- Fishell G.
- Karayannis T.
- Au E.
- Patel J.C.
- Kruglikov I.
- Markx S.
- Delorme R.
- Héron D.
- Salomon D.
- Glessner J.
- Restituito S.
- Gordon A.
- Rodriguez-Murillo L.
- Roy N.C.
- Gogos J.A.
- Rudy B.
- Rice M.E.
- Karayiorgou M.
- Hakonarson H.
- Keren B.
- Huguet G.
- Bourgeron T.
- Hoeffer C.
- Tsien R.W.
- Peles E.
- Fishell G.
Bipolar Disorder
Major Depressive Disorder
- Howard D.M.
- Adams M.J.
- Shirali M.
- Clarke T.K.
- Marioni R.E.
- Davies G.
- Coleman J.R.I.
- Alloza C.
- Shen X.
- Barbu M.C.
- Wigmore E.M.
- Gibson J.
- Hagenaars S.P.
- Lewis C.M.
- Ward J.
- Smith D.J.
- Sullivan P.F.
- Haley C.S.
- Breen G.
- Deary I.J.
- McIntosh A.M.
Multiple Sclerosis
- Tiwari H.
- Patki A.
- Cofield S.S.
- Gustafson T.
- Duggan D.
- Jacobson S.
- Wolinsky J.S.
- Lublin F.D.
- Cutter G.R.
GWAS on relapse outcomes in CombiRx trial Poster presented at: 31st Congress of European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Barcelona, Spain, October 7-10.
Inflammatory Diseases
- Franke A.
- Hampe J.
- Rosenstiel P.
- Becker C.
- Wagner F.
- Häsler R.
- Little R.D.
- Huse K.
- Ruether A.
- Balschun T.
- Wittig M.
- ElSharawy A.
- Mayr G.
- Albrecht M.
- Prescott N.J.
- Onnie C.M.
- Fournier H.
- Keith T.
- Radelof U.
- Platzer M.
- Mathew C.G.
- Stoll M.
- Krawczak M.
- Nürnberg P.
- Schreiber S.
Inflammatory Bowel Disease
- Franke A.
- Hampe J.
- Rosenstiel P.
- Becker C.
- Wagner F.
- Häsler R.
- Little R.D.
- Huse K.
- Ruether A.
- Balschun T.
- Wittig M.
- ElSharawy A.
- Mayr G.
- Albrecht M.
- Prescott N.J.
- Onnie C.M.
- Fournier H.
- Keith T.
- Radelof U.
- Platzer M.
- Mathew C.G.
- Stoll M.
- Krawczak M.
- Nürnberg P.
- Schreiber S.
- Franke A.
- Hampe J.
- Rosenstiel P.
- Becker C.
- Wagner F.
- Häsler R.
- Little R.D.
- Huse K.
- Ruether A.
- Balschun T.
- Wittig M.
- ElSharawy A.
- Mayr G.
- Albrecht M.
- Prescott N.J.
- Onnie C.M.
- Fournier H.
- Keith T.
- Radelof U.
- Platzer M.
- Mathew C.G.
- Stoll M.
- Krawczak M.
- Nürnberg P.
- Schreiber S.
- Franke A.
- Hampe J.
- Rosenstiel P.
- Becker C.
- Wagner F.
- Häsler R.
- Little R.D.
- Huse K.
- Ruether A.
- Balschun T.
- Wittig M.
- ElSharawy A.
- Mayr G.
- Albrecht M.
- Prescott N.J.
- Onnie C.M.
- Fournier H.
- Keith T.
- Radelof U.
- Platzer M.
- Mathew C.G.
- Stoll M.
- Krawczak M.
- Nürnberg P.
- Schreiber S.
- Franke A.
- Hampe J.
- Rosenstiel P.
- Becker C.
- Wagner F.
- Häsler R.
- Little R.D.
- Huse K.
- Ruether A.
- Balschun T.
- Wittig M.
- ElSharawy A.
- Mayr G.
- Albrecht M.
- Prescott N.J.
- Onnie C.M.
- Fournier H.
- Keith T.
- Radelof U.
- Platzer M.
- Mathew C.G.
- Stoll M.
- Krawczak M.
- Nürnberg P.
- Schreiber S.
- Pepe J.
- Zawadynski S.
- Herrmann F.R.
- Juillerat P.
- Michetti P.
- Ferrari-Lacraz S.
- Belli D.
- Ratib O.
- Rizzoli R.
- Chevalley T.
- Ferrari S.L.
- Pepe J.
- Zawadynski S.
- Herrmann F.R.
- Juillerat P.
- Michetti P.
- Ferrari-Lacraz S.
- Belli D.
- Ratib O.
- Rizzoli R.
- Chevalley T.
- Ferrari S.L.
- Franke A.
- Hampe J.
- Rosenstiel P.
- Becker C.
- Wagner F.
- Häsler R.
- Little R.D.
- Huse K.
- Ruether A.
- Balschun T.
- Wittig M.
- ElSharawy A.
- Mayr G.
- Albrecht M.
- Prescott N.J.
- Onnie C.M.
- Fournier H.
- Keith T.
- Radelof U.
- Platzer M.
- Mathew C.G.
- Stoll M.
- Krawczak M.
- Nürnberg P.
- Schreiber S.

Chronic Periodontitis
- Sanders A.E.
- Sofer T.
- Wong Q.
- Kerr K.F.
- Agler C.
- Shaffer J.R.
- Beck J.D.
- Offenbacher S.
- Salazar C.R.
- North K.E.
- Marazita M.L.
- Laurie C.C.
- Singer R.H.
- Cai J.
- Finlayson T.L.
- Divaris K.
- Sanders A.E.
- Sofer T.
- Wong Q.
- Kerr K.F.
- Agler C.
- Shaffer J.R.
- Beck J.D.
- Offenbacher S.
- Salazar C.R.
- North K.E.
- Marazita M.L.
- Laurie C.C.
- Singer R.H.
- Cai J.
- Finlayson T.L.
- Divaris K.
Acute Otitis Media
- Van Ingen G.
- Li J.
- Goedegebure A.
- Pandey R.
- Rose Li Y.
- March M.E.
- Jaddoe V.W.V.
- Bakay M.
- Mentch F.D.
- Thomas K.
- Wei Z.
- Chang X.
- Hain H.S.
- Uitterlinden A.G.
- Moll H.A.
- Van Duijn C.M.
- Rivadeneira F.
- Raat H.
- De Jong R.J.B.
- Sleiman P.M.
- Van Der Schroeff M.P.
- Hakonarson H.
- Van Ingen G.
- Li J.
- Goedegebure A.
- Pandey R.
- Rose Li Y.
- March M.E.
- Jaddoe V.W.V.
- Bakay M.
- Mentch F.D.
- Thomas K.
- Wei Z.
- Chang X.
- Hain H.S.
- Uitterlinden A.G.
- Moll H.A.
- Van Duijn C.M.
- Rivadeneira F.
- Raat H.
- De Jong R.J.B.
- Sleiman P.M.
- Van Der Schroeff M.P.
- Hakonarson H.
- Van Ingen G.
- Li J.
- Goedegebure A.
- Pandey R.
- Rose Li Y.
- March M.E.
- Jaddoe V.W.V.
- Bakay M.
- Mentch F.D.
- Thomas K.
- Wei Z.
- Chang X.
- Hain H.S.
- Uitterlinden A.G.
- Moll H.A.
- Van Duijn C.M.
- Rivadeneira F.
- Raat H.
- De Jong R.J.B.
- Sleiman P.M.
- Van Der Schroeff M.P.
- Hakonarson H.
- Van Ingen G.
- Li J.
- Goedegebure A.
- Pandey R.
- Rose Li Y.
- March M.E.
- Jaddoe V.W.V.
- Bakay M.
- Mentch F.D.
- Thomas K.
- Wei Z.
- Chang X.
- Hain H.S.
- Uitterlinden A.G.
- Moll H.A.
- Van Duijn C.M.
- Rivadeneira F.
- Raat H.
- De Jong R.J.B.
- Sleiman P.M.
- Van Der Schroeff M.P.
- Hakonarson H.
Non–Small Cell Lung Cancer
- Wu X.
- Wang L.
- Ye Y.
- Aakre J.A.
- Pu X.
- Chang G.C.
- Yang P.C.
- Roth J.A.
- Marks R.S.
- Lippman S.M.
- Chang J.Y.
- Lu C.
- Deschamps C.
- Su W.C.
- Wang W.C.
- Huang M.S.
- Chang D.W.
- Li Y.
- Pankratz V.S.
- Minna J.D.
- Hong W.K.
- Hildebrandt M.A.T.
- Hsiung C.A.
- Yang P.
- Wu X.
- Wang L.
- Ye Y.
- Aakre J.A.
- Pu X.
- Chang G.C.
- Yang P.C.
- Roth J.A.
- Marks R.S.
- Lippman S.M.
- Chang J.Y.
- Lu C.
- Deschamps C.
- Su W.C.
- Wang W.C.
- Huang M.S.
- Chang D.W.
- Li Y.
- Pankratz V.S.
- Minna J.D.
- Hong W.K.
- Hildebrandt M.A.T.
- Hsiung C.A.
- Yang P.
- Jin Z.
- Mori Y.
- Yang J.
- Sato F.
- Ito T.
- Cheng Y.
- Paun B.
- Hamilton J.P.
- Kan T.
- Olaru A.
- David S.
- Agarwal R.
- Abraham J.M.
- Beer D.
- Montgomery E.
- Meltzer S.J.
- Jin Z.
- Mori Y.
- Yang J.
- Sato F.
- Ito T.
- Cheng Y.
- Paun B.
- Hamilton J.P.
- Kan T.
- Olaru A.
- David S.
- Agarwal R.
- Abraham J.M.
- Beer D.
- Montgomery E.
- Meltzer S.J.
- Jin Z.
- Mori Y.
- Yang J.
- Sato F.
- Ito T.
- Cheng Y.
- Paun B.
- Hamilton J.P.
- Kan T.
- Olaru A.
- David S.
- Agarwal R.
- Abraham J.M.
- Beer D.
- Montgomery E.
- Meltzer S.J.
Other Human Disorders
Conclusions and Future Perspectives

- Galesloot T.E.
- Verweij N.
- Traglia M.
- Barbieri C.
- Van F.
- Geurts-Moespot A.J.
- Girelli D.
- Kiemeney L.A.L.M.
- Sweep F.C.G.J.
- Swertz M.A.
- Van Der Meer P.
- Camaschella C.
- Toniolo D.
- Vermeulen S.H.
- Van Der Harst P.
- Swinkels D.W.
Acknowledgments
Author Contributions
References
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Article Info
Publication History
Footnotes
Supported by NIH grants R01AR066782 (K.T.), R01AR068835 and R01AR061399 (C.S.), and R01DE029353 (C.S., X.Z.); UCLA / NIH CTSI grant UL1TR000124 (X.Z.); National Natural Science Foundation of China grant 81974147 (B.S.); National Natural Science Foundation of China grant 82001031 (X.C.); and West China School of Stomatology of Sichuan University grant RD-03-2020007 (B.S.).
Disclosures: X.Z., K.T., and C.S. are inventors of NELL1–related patents. X.Z., K.T., and C.S. are founders or former board members of Bone Biologics Inc./Bone Biologics Corp., which sublicenses Nell-1 patents from UC Regents, which also holds equity in the company. The authors declare no other potential conflicts of interest with respect to the authorship and publication of this article.