The 2025 Connect & Collaborate Okur–Chung Neurodevelopmental Syndrome (OCNDS) Scientific and Family Conference convened researchers, clinicians, and families to accelerate discovery and translation of research for OCNDS. OCNDS is an ultra-rare disorder caused by pathogenic variants in the CSNK2A1 gene. Nearly 200 participants joined the 4-day event featuring 17 scientific talks, 15 family sessions, and multiple roundtables integrating patient and researcher perspectives. Scientific sessions covered CK2 biology, variant functional studies, model organism pipelines, and early therapeutic exploration. Family sessions emphasized speech and language outcomes, sleep and behavioral challenges, and barriers to clinical care. Crowdsourced researcher-family dialogues identified shared priorities for the next research phase, including developing measurable clinical endpoints, expanding biobanking and variant data infrastructure, and focusing on translational models to enable preclinical testing. These priorities will steer the next several years of OCNDS research and collaboration, driving coordinated advances toward clinical translation.
OkurVChoMTHendersonL, et al.De novo mutations in CSNK2A1 are associated with neurodevelopmental abnormalities and dysmorphic features. Hum Genet2016; 135(7): 699–705. https://doi.org/10.1007/s00439-016-1661-y
2.
LitchfieldDW. Protein kinase CK2: structure, regulation and role in cellular decisions of life and death. Biochem J2003; 369(Pt 1): 1–15. https://doi.org/10.1042/BJ20021469
MeggioFPinnaLA. One-thousand-and-one substrates of protein kinase CK2?J Off Publ Fed Am Soc Exp Biol2003; 17(3): 349–368. https://doi.org/10.1096/fj.02-0473rev
8.
GyenisLMenyhartDCruiseES, et al.Chemical genetic validation of CSNK2 substrates using an inhibitor-resistant mutant in combination with triple SILAC quantitative phosphoproteomics. Front Mol Biosci2022; 9: 909711. https://doi.org/10.3389/fmolb.2022.909711
9.
MenyhartDGyenisLJurcicK, et al.Comparison of CX-4945 and SGC-CK2-1 as inhibitors of CSNK2 using quantitative phosphoproteomics: triple SILAC in combination with inhibitor-resistant CSNK2. Curr Res Chem Biol2023; 3: 100041. https://doi.org/10.1016/j.crchbi.2023.100041
10.
GratzAGötzCJoseJ. A CE-based assay for human protein kinase CK2 activity measurement and inhibitor screening. Electrophoresis2010; 31(4): 634–640. https://doi.org/10.1002/elps.200900514
11.
DominguezICruz-GameroJMCorasollaV, et al.Okur-Chung neurodevelopmental syndrome-linked CK2α variants have reduced kinase activity. Hum Genet2021; 140(7): 1077–1096. https://doi.org/10.1007/s00439-021-02280-5
12.
Cruz-GameroJMBallardinDLecisB, et al.Missense mutation in the activation segment of the kinase CK2 models Okur-Chung neurodevelopmental disorder and alters the hippocampal glutamatergic synapse. Mol Psychiatr2024; 30(4): 1497–1509. https://doi.org/10.1038/s41380-024-02762-8
13.
GastASchreiberSJoseJ. Rapid method for evaluation of CK2 enzymatic activity and CK2α/CK2β-interaction in Escherichia coli cell lysates. Biol Chem2025; 406(3–4): 117–124. https://doi.org/10.1515/hsz-2024-0159
14.
IssingerOGBrockelCBoldyreffB, et al.Characterization of the alpha and beta subunits of casein kinase 2 by far-UV CD spectroscopy. Biochemistry1992; 31(26): 6098–6103. https://doi.org/10.1021/bi00141a020
15.
NiefindKRaafJIssingerOG. Protein kinase CK2 in health and disease: protein kinase CK2: from structures to insights. Cell Mol Life Sci CMLS2009; 66(11–12): 1800–1816. https://doi.org/10.1007/s00018-009-9149-8
16.
UnniPFriendJWeinbergJ, et al.Predictive functional, statistical and structural analysis of CSNK2A1 and CSNK2B variants linked to neurodevelopmental diseases. Front Mol Biosci2022; 9: 851547. https://doi.org/10.3389/fmolb.2022.851547
LouDYDominguezIToselliP, et al.The alpha catalytic subunit of protein kinase CK2 is required for mouse embryonic development. Mol Cell Biol2008; 28(1): 131–139. https://doi.org/10.1128/MCB.01119-07
20.
GoetzSCLiemKFAndersonKV. The spinocerebellar ataxia-associated gene Tau Tubulin kinase 2 controls the initiation of ciliogenesis. Cell2012; 151(4): 847–858. https://doi.org/10.1016/j.cell.2012.10.010
21.
LoukilABarringtonCGoetzSC. A complex of distal appendage–associated kinases linked to human disease regulates ciliary trafficking and stability. Proc Natl Acad Sci2021; 118(16): e2018740118. https://doi.org/10.1073/pnas.2018740118
22.
FuccilloMJoynerALFishellG. Morphogen to mitogen: the multiple roles of hedgehog signaling in vertebrate neural development. Nat Rev Neurosci2006; 7(10): 772–783. https://doi.org/10.1038/nrn1990
LinJMKilmanVLKeeganK, et al.A role for casein kinase 2alpha in the Drosophila circadian clock. Nature2002; 420(6917): 816–820. https://doi.org/10.1038/nature01235
28.
SmithEMLinJMMeissnerRA, et al.Dominant-negative CK2αlpha induces potent effects on circadian rhythmicity. PLoS Genet2008; 4(1): e12. https://doi.org/10.1371/journal.pgen.0040012
29.
LiYKellerDMScottJD, et al.CK2 phosphorylates SSRP1 and inhibits its DNA-Binding activity. J Biol Chem2005; 280(12): 11869–11875. https://doi.org/10.1074/jbc.M413944200
30.
MeissnerRAKilmanVLLinJM, et al.TIMELESS is an important mediator of CK2 effects on circadian clock function in vivo. J Neurosci Off J Soc Neurosci2008; 28(39): 9732–9740. https://doi.org/10.1523/JNEUROSCI.0840-08.2008
31.
MaierBWendtSVanselowJT, et al.A large-scale functional RNAi screen reveals a role for CK2 in the Mammalian circadian clock. Genes Dev2009; 23(6): 708–718. https://doi.org/10.1101/gad.512209
32.
UmemuraYYoshidaJWadaM, et al.An in vitro ES cell-based clock recapitulation assay model identifies CK2α as an endogenous clock regulator. PLoS One2013; 8(6): e67241. https://doi.org/10.1371/journal.pone.0067241
33.
TsuchiyaYAkashiMMatsudaM, et al.Involvement of the protein kinase CK2 in the regulation of Mammalian circadian rhythms. Sci Signal2009; 2(73): ra26. https://doi.org/10.1126/scisignal.2000305
34.
CaeferDMPhanNQLiddleJC, et al.The Okur-Chung Neurodevelopmental syndrome mutation CK2K198R leads to a rewiring of kinase specificity. Front Mol Biosci2022; 9: 850661. https://doi.org/10.3389/fmolb.2022.850661
ErnstMEBaughEHThomasA, et al.CSNK2B: a broad spectrum of neurodevelopmental disability and epilepsy severity. Epilepsia2021; 62(7): e103–e109. https://doi.org/10.1111/epi.16931
39.
LippaNMulhernMErnst FloridoM, et al.CSNK2B-Related neurodevelopmental disorder. In: AdamMPFeldmanJMirzaaGM, et al. (eds). GeneReviews® [Internet]. University of Washington, Seattle, 2024. https://www.ncbi.nlm.nih.gov/books/NBK606532/
40.
SahooPKLeeSJJaiswalPB, et al.Axonal G3BP1 stress granule protein limits axonal mRNA translation and nerve regeneration. Nat Commun2018; 9(1): 3358. https://doi.org/10.1038/s41467-018-05647-x
41.
SahooPKKarANSamraN, et al.A Ca2+-Dependent switch activates axonal casein kinase 2α translation and drives G3BP1 granule disassembly for axon regeneration. Curr Biol2020; 30(24): 4882–4895.e6. https://doi.org/10.1016/j.cub.2020.09.043
42.
NanHChuMZhangJ, et al.Okur‐Chung neurodevelopmental syndrome: implications for phenotype and genotype expansion. Mol Genet Genom Med2024; 12(3): e2398. https://doi.org/10.1002/mgg3.2398
