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NSD1  -  nuclear receptor binding SET domain protein 1

Homo sapiens

 
 
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Disease relevance of NSD1

 

Psychiatry related information on NSD1

 

High impact information on NSD1

  • We isolated NSD1 from the 5q35 breakpoint in an individual with Sotos syndrome harboring a chromosomal translocation [7].
  • Homozygous mutant NSD1 embryos, which initiate mesoderm formation, display a high incidence of apoptosis and fail to complete gastrulation, indicating that NSD1 is a developmental regulatory protein that exerts function(s) essential for early post-implantation development [8].
  • We reviewed the clinical phenotypes of 239 NSD1-positive individuals [9].
  • The reasons for the low vertical transmission rate are unclear, although familial cases were more likely than nonfamilial cases (P = .005) to carry missense mutations, suggesting that the underlying NSD1 mutational mechanism in Sotos syndrome may influence reproductive fitness [9].
  • These results suggest that the two disorders may have more similarities than previously thought and that NSD1 could be involved in imprinting of the chromosome 11p15 region [10].
 

Biological context of NSD1

  • Thus, Nizp1 contains a novel type of zinc finger motif that functions as a docking site for NSD1 and is more than just a degenerate evolutionary remnant of a C2H2 motif [11].
  • It has been shown that the major cause of SoS is haploinsufficiency of the NSD1 gene at 5q35, because the majority of patients had either a common microdeletion including NSD1 or a truncated type of point mutation in NSD1 [12].
  • Truncating NSD1 mutations occurred throughout the gene, but pathogenic missense mutations occurred only in functional domains (P < 2 x 10(-16)) [9].
  • Breakpoint mapping by FISH and reverse transcriptase polymerase chain reaction (RT-PCR) analysis confirmed that this was the same t(5;11) as previously identified in 3 children with AML, associated with del(5q) and resulting in the NUP98-NSD1 gene fusion [13].
  • NSD1 consists of at least 23 exons [14].
 

Anatomical context of NSD1

 

Associations of NSD1 with chemical compounds

  • The NSD1 gene product is a SET-domain histone lysine methyltransferase that has previously been shown to interact with nuclear receptors [11].
  • Mutations of the cysteine or histidine residues in the C2HR motif abolish the interaction of Nizp1 with NSD1 and compromise the ability of Nizp1 to repress transcription [11].
  • Yeast two-hybrid and glutathione S-transferase pull-down assays show that both the N and C terminus of ARA267-alpha interact with the AR DNA- and ligand-binding domains [17].
  • Luciferase and chloramphenicol acetyltransferase assays show that ARA267-alpha can enhance AR transactivation in a dihydrotestosterone-dependent manner in PC-3 and H1299 cells [17].
  • Our finding implied that androgen signaling pathway might cross talk with apoptosis signaling pathway through the interaction between ARA267-alpha and DR6 [18].
 

Physical interactions of NSD1

 

Other interactions of NSD1

  • The reciprocal transcript, NSD1-NUP98, was also detected by reverse transcriptase--polymerase chain reaction [1].
  • By using 3'--rapid amplification of complementary DNA ends (3'-RACE) polymerase chain reaction, we identified a chimeric messenger RNA that results in the in-frame fusion of NUP98 to a novel gene, NSD1 [1].
  • The NSD1(+/+) patients did not differ from the reference, with the exception of the mean IGFBP-3 level (-1.3) [15].
  • OBJECTIVE: To investigate the effect of nuclear receptor Su-var, 3-9, enhancer of zeste, trithorax (SET) domain-containing protein 1 (NSD1) gene alteration in patients with Sotos syndrome on plasma IGFs and IGF-binding proteins (IGFBPs), as well as on the IGF/IGFBP system activity at the tissue level [15].
  • Identification and characterization of a novel androgen receptor coregulator ARA267-alpha in prostate cancer cells [17].
 

Analytical, diagnostic and therapeutic context of NSD1

References

  1. A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia. Jaju, R.J., Fidler, C., Haas, O.A., Strickson, A.J., Watkins, F., Clark, K., Cross, N.C., Cheng, J.F., Aplan, P.D., Kearney, L., Boultwood, J., Wainscoat, J.S. Blood (2001) [Pubmed]
  2. Cryptic insertion producing two NUP98/NSD1 chimeric transcripts in adult refractory anemia with an excess of blasts. La Starza, R., Gorello, P., Rosati, R., Riezzo, A., Veronese, A., Ferrazzi, E., Martelli, M.F., Negrini, M., Mecucci, C. Genes Chromosomes Cancer (2004) [Pubmed]
  3. Familial gigantism caused by an NSD1 mutation. van Haelst, M.M., Hoogeboom, J.J., Baujat, G., Brüggenwirth, H.T., Van de Laar, I., Coleman, K., Rahman, N., Niermeijer, M.F., Drop, S.L., Scambler, P.J. Am. J. Med. Genet. A (2005) [Pubmed]
  4. Clinical and molecular overlap in overgrowth syndromes. Baujat, G., Rio, M., Rossignol, S., Sanlaville, D., Lyonnet, S., Le Merrer, M., Munnich, A., Gicquel, C., Colleaux, L., Cormier-Daire, V. American journal of medical genetics. Part C, Seminars in medical genetics. (2005) [Pubmed]
  5. Spectrum of NSD1 mutations in Sotos and Weaver syndromes. Rio, M., Clech, L., Amiel, J., Faivre, L., Lyonnet, S., Le Merrer, M., Odent, S., Lacombe, D., Edery, P., Brauner, R., Raoul, O., Gosset, P., Prieur, M., Vekemans, M., Munnich, A., Colleaux, L., Cormier-Daire, V. J. Med. Genet. (2003) [Pubmed]
  6. Hearing recovery following large and small fenestra stapes surgery for otosclerosis. Naramura, H., Kubo, T., Asai, H., Shiraishi, T., Matsunaga, T. Acta oto-laryngologica. Supplementum. (1993) [Pubmed]
  7. Haploinsufficiency of NSD1 causes Sotos syndrome. Kurotaki, N., Imaizumi, K., Harada, N., Masuno, M., Kondoh, T., Nagai, T., Ohashi, H., Naritomi, K., Tsukahara, M., Makita, Y., Sugimoto, T., Sonoda, T., Hasegawa, T., Chinen, Y., Tomita Ha, H.A., Kinoshita, A., Mizuguchi, T., Yoshiura Ki, K., Ohta, T., Kishino, T., Fukushima, Y., Niikawa, N., Matsumoto, N. Nat. Genet. (2002) [Pubmed]
  8. NSD1 is essential for early post-implantation development and has a catalytically active SET domain. Rayasam, G.V., Wendling, O., Angrand, P.O., Mark, M., Niederreither, K., Song, L., Lerouge, T., Hager, G.L., Chambon, P., Losson, R. EMBO J. (2003) [Pubmed]
  9. Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations. Tatton-Brown, K., Douglas, J., Coleman, K., Baujat, G., Cole, T.R., Das, S., Horn, D., Hughes, H.E., Temple, I.K., Faravelli, F., Waggoner, D., Turkmen, S., Cormier-Daire, V., Irrthum, A., Rahman, N. Am. J. Hum. Genet. (2005) [Pubmed]
  10. Paradoxical NSD1 mutations in Beckwith-Wiedemann syndrome and 11p15 anomalies in Sotos syndrome. Baujat, G., Rio, M., Rossignol, S., Sanlaville, D., Lyonnet, S., Le Merrer, M., Munnich, A., Gicquel, C., Cormier-Daire, V., Colleaux, L. Am. J. Hum. Genet. (2004) [Pubmed]
  11. Nizp1, a novel multitype zinc finger protein that interacts with the NSD1 histone lysine methyltransferase through a unique C2HR motif. Nielsen, A.L., Jørgensen, P., Lerouge, T., Cerviño, M., Chambon, P., Losson, R. Mol. Cell. Biol. (2004) [Pubmed]
  12. Preferential paternal origin of microdeletions caused by prezygotic chromosome or chromatid rearrangements in Sotos syndrome. Miyake, N., Kurotaki, N., Sugawara, H., Shimokawa, O., Harada, N., Kondoh, T., Tsukahara, M., Ishikiriyama, S., Sonoda, T., Miyoshi, Y., Sakazume, S., Fukushima, Y., Ohashi, H., Nagai, T., Kawame, H., Kurosawa, K., Touyama, M., Shiihara, T., Okamoto, N., Nishimoto, J., Yoshiura, K., Ohta, T., Kishino, T., Niikawa, N., Matsumoto, N. Am. J. Hum. Genet. (2003) [Pubmed]
  13. A cryptic t(5;11)(q35;p15.5) in 2 children with acute myeloid leukemia with apparently normal karyotypes, identified by a multiplex fluorescence in situ hybridization telomere assay. Brown, J., Jawad, M., Twigg, S.R., Saracoglu, K., Sauerbrey, A., Thomas, A.E., Eils, R., Harbott, J., Kearney, L. Blood (2002) [Pubmed]
  14. Molecular characterization of NSD1, a human homologue of the mouse Nsd1 gene. Kurotaki, N., Harada, N., Yoshiura, K., Sugano, S., Niikawa, N., Matsumoto, N. Gene (2001) [Pubmed]
  15. Mutations in the NSD1 gene in patients with Sotos syndrome associate with endocrine and paracrine alterations in the IGF system. De Boer, L., Van Duyvenvoorde, H.A., Willemstein-Van Hove, E.C., Hoogerbrugge, C.M., Van Doorn, J., Maassen, J.A., Karperien, M., Wit, J.M. Eur. J. Endocrinol. (2004) [Pubmed]
  16. Nevo syndrome with an NSD1 deletion: a variant of Sotos syndrome? Kanemoto, N., Kanemoto, K., Nishimura, G., Kamoda, T., Visser, R., Shimokawa, O., Matsumoto, N. Am. J. Med. Genet. A (2006) [Pubmed]
  17. Identification and characterization of a novel androgen receptor coregulator ARA267-alpha in prostate cancer cells. Wang, X., Yeh, S., Wu, G., Hsu, C.L., Wang, L., Chiang, T., Yang, Y., Guo, Y., Chang, C. J. Biol. Chem. (2001) [Pubmed]
  18. Androgen receptor coregulator ARA267-alpha interacts with death receptor-6 revealed by the yeast two-hybrid. Mai, T., Wang, X., Zhang, Z., Xin, D., Na, Y., Guo, Y. Sci. China, C, Life Sci. (2004) [Pubmed]
  19. NUP98-NSD1 links H3K36 methylation to Hox-A gene activation and leukaemogenesis. Wang, G.G., Cai, L., Pasillas, M.P., Kamps, M.P. Nat. Cell Biol. (2007) [Pubmed]
  20. dHPLC screening of the NSD1 gene identifies nine novel mutations--summary of the first 100 Sotos syndrome mutations. Melchior, L., Schwartz, M., Duno, M. Ann. Hum. Genet. (2005) [Pubmed]
  21. Partial NSD1 deletions cause 5% of Sotos syndrome and are readily identifiable by multiplex ligation dependent probe amplification. Douglas, J., Tatton-Brown, K., Coleman, K., Guerrero, S., Berg, J., Cole, T.R., Fitzpatrick, D., Gillerot, Y., Hughes, H.E., Pilz, D., Raymond, F.L., Temple, I.K., Irrthum, A., Schouten, J.P., Rahman, N. J. Med. Genet. (2005) [Pubmed]
  22. Translocation between chromosome 5q35 and chromosome 11q13-- an unusual cytogenetic finding in a primary refractory acute myeloid leukemia. Wang, T.F., Horsley, S.W., Lee, K.F., Chu, S.C., Li, C.C., Kao, R.H. Clinical and laboratory haematology. (2006) [Pubmed]
  23. A human monoclonal autoantibody to platelet glycoprotein IIb derived from normal human lymphocytes. Denomme, G.A., Smith, J.W., Kelton, J.G., Bell, D.A. Blood (1992) [Pubmed]
 
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