Gene Symbol: D123
Description: cell division cycle 123
Alias: C10orf7, D123, cell division cycle protein 123 homolog, HT-1080, PZ32, cell division cycle 123 homolog
Species: human
Products:     D123

Top Publications

  1. Grarup N, Andersen G, Krarup N, Albrechtsen A, Schmitz O, Jørgensen T, et al. Association testing of novel type 2 diabetes risk alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 loci with insulin release, insulin sensitivity, and obesity in a population-based sample of 4,516 glucose-tolerant middle-aged D. Diabetes. 2008;57:2534-40 pubmed publisher
  2. Zeggini E, Scott L, Saxena R, Voight B, Marchini J, Hu T, et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008;40:638-45 pubmed publisher
    ..1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D. ..
  3. Staiger H, Machicao F, Kantartzis K, Schäfer S, Kirchhoff K, Guthoff M, et al. Novel meta-analysis-derived type 2 diabetes risk loci do not determine prediabetic phenotypes. PLoS ONE. 2008;3:e3019 pubmed publisher
    ..Possible weak effects of ADAMTS9 SNP rs4607103 and VEGFA SNP rs9472138 on insulin sensitivity and insulin secretion, respectively, await further confirmation by larger studies. ..
  4. Lyssenko V, Jonsson A, Almgren P, Pulizzi N, Isomaa B, Tuomi T, et al. Clinical risk factors, DNA variants, and the development of type 2 diabetes. N Engl J Med. 2008;359:2220-32 pubmed publisher
    ..The value of genetic factors increased with an increasing duration of follow-up. ..
  5. Lin X, Song K, Lim N, Yuan X, Johnson T, Abderrahmani A, et al. Risk prediction of prevalent diabetes in a Swiss population using a weighted genetic score--the CoLaus Study. Diabetologia. 2009;52:600-8 pubmed publisher
    ..In this population, a simple weighted 15 SNP-based genetic score provides additional information over clinical predictors of prevalent diabetes. At this stage, however, the clinical benefit of this genetic information is limited. ..
  6. Sanghera D, Been L, Ortega L, Wander G, Mehra N, Aston C, et al. Testing the association of novel meta-analysis-derived diabetes risk genes with type II diabetes and related metabolic traits in Asian Indian Sikhs. J Hum Genet. 2009;54:162-8 pubmed publisher
    ..To our knowledge, this is the first study reporting the role of recently emerging loci in this high-risk population from the South Asian subcontinent. ..
  7. Stancakova A, Kuulasmaa T, Paananen J, Jackson A, Bonnycastle L, Collins F, et al. Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 nondiabetic Finnish men. Diabetes. 2009;58:2129-36 pubmed publisher
    ..Effects of SLC30A8, HHEX, CDKAL1, and TCF7L2 on insulin release could be partially explained by impaired proinsulin conversion. HHEX might influence both insulin release and insulin sensitivity. ..
  8. Bieganowski P, Shilinski K, Tsichlis P, Brenner C. Cdc123 and checkpoint forkhead associated with RING proteins control the cell cycle by controlling eIF2gamma abundance. J Biol Chem. 2004;279:44656-66 pubmed
    ..cdc123, homolog of mammalian D123, is a new cell division cycle mutant with a G2 delay at permissive temperature and a terminal, mating-proficient G1 ..
  9. Lango H, Palmer C, Morris A, Zeggini E, Hattersley A, McCarthy M, et al. Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk. Diabetes. 2008;57:3129-35 pubmed publisher
    ..Further studies are needed to assess whether individuals with extreme numbers of risk alleles may benefit from genetic testing. ..

More Information


  1. Meigs J, Shrader P, Sullivan L, McAteer J, Fox C, Dupuis J, et al. Genotype score in addition to common risk factors for prediction of type 2 diabetes. N Engl J Med. 2008;359:2208-19 pubmed publisher
    ..A genotype score based on 18 risk alleles predicted new cases of diabetes in the community but provided only a slightly better prediction of risk than knowledge of common risk factors alone. ..
  2. Perzlmaier A, Richter F, Seufert W. Translation initiation requires cell division cycle 123 (Cdc123) to facilitate biogenesis of the eukaryotic initiation factor 2 (eIF2). J Biol Chem. 2013;288:21537-46 pubmed publisher
    ..This work identifies a novel step in the eukaryotic translation initiation pathway and assigns a biochemical function to a protein that is essential for growth and viability of eukaryotic cells. ..
  3. Shu X, Long J, Cai Q, Qi L, Xiang Y, Cho Y, et al. Identification of new genetic risk variants for type 2 diabetes. PLoS Genet. 2010;6:e1001127 pubmed publisher
    ..Our study provides strong evidence for a novel T2D susceptibility locus at 13q31.1 and the presence of new independent risk variants near regions (10p13 and 15q22.2) reported by previous GWAS. ..
  4. An M, Kim D, Kim C, Kim M, Rhee S, Seo S, et al. Histone demethylase KDM3B regulates the transcriptional network of cell-cycle genes in hepatocarcinoma HepG2 cells. Biochem Biophys Res Commun. 2019;508:576-582 pubmed publisher
    ..The results implicate KDM3B as a crucial epigenetic factor in cell cycle regulation that manipulates chromatin dynamics and transcription in HCC, and identifies a potential gene therapy target for effective treatment of HCC. ..
  5. Fogarty M, Cannon M, Vadlamudi S, Gaulton K, Mohlke K. Identification of a regulatory variant that binds FOXA1 and FOXA2 at the CDC123/CAMK1D type 2 diabetes GWAS locus. PLoS Genet. 2014;10:e1004633 pubmed publisher
    ..These results suggest that rs11257655 affects transcriptional activity through altered binding of a protein complex that includes FOXA1 and FOXA2, providing a potential molecular mechanism at this GWAS locus. ..
  6. Lara Riegos J, Ortiz López M, Peña Espinoza B, Montúfar Robles I, Peña Rico M, Sánchez Pozos K, et al. Diabetes susceptibility in Mayas: Evidence for the involvement of polymorphisms in HHEX, HNF4α, KCNJ11, PPARγ, CDKN2A/2B, SLC30A8, CDC123/CAMK1D, TCF7L2, ABCA1 and SLC16A11 genes. Gene. 2015;565:68-75 pubmed publisher
    ..In conclusion, these findings support an association of genetic polymorphisms to develop T2D in Maya population. ..
  7. Carossino M, Barrandeguy M, Li Y, Parreño V, Janes J, Loynachan A, et al. Detection, molecular characterization and phylogenetic analysis of G3P[12] and G14P[12] equine rotavirus strains co-circulating in central Kentucky. Virus Res. 2018;255:39-54 pubmed publisher
    ..These may constitute ideal reference strains to comparatively study the molecular biology of G3 and G14 strains and perform vaccine efficacy studies following heterologous challenge in the future. ..
  8. Chung S, Kim M, Kim J, Ryu H, Kim Y, Kim S, et al. Association of type 2 diabetes GWAS loci and the risk of Parkinson's and Alzheimer's diseases. Parkinsonism Relat Disord. 2015;21:1435-40 pubmed publisher
    ..Our results suggest that genome-wide significant loci of T2DM play no major role in the risk and cognitive impairment of PD and AD. ..
  9. Miller S, Melén E, Merid S, Hall I, Sayers I. Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development. Respir Res. 2016;17:95 pubmed publisher
    ..Our data provides a systematic evaluation of lung function associated genes in this context and offers some insight into the potential role of several of these genes in contributing to human lung development. ..
  10. Panvert M, Dubiez E, Arnold L, Perez J, Mechulam Y, Seufert W, et al. Cdc123, a Cell Cycle Regulator Needed for eIF2 Assembly, Is an ATP-Grasp Protein with Unique Features. Structure. 2015;23:1596-1608 pubmed publisher
    ..A docking of eIF2αγ onto Cdc123, combined with genetic and biochemical experiments, allows us to propose a model explaining how Cdc123 participates in the biogenesis of eIF2 through facilitating assembly of eIF2γ to eIF2α. ..
  11. Su H, Sheng X, Liu Y. Insights into the catalytic mechanism of N-acetylglucosaminidase glycoside hydrolase from Bacillus subtilis: a QM/MM study. Org Biomol Chem. 2016;14:3432-42 pubmed publisher
    ..and the substrate distortion in the active site can significantly facilitate the reaction, in which residue D123 plays a key role in this distortion...
  12. Tarnowski M, Malinowski D, Safranow K, Dziedziejko V, Pawlik A. CDC123/CAMK1D gene rs12779790 polymorphism and rs10811661 polymorphism upstream of the CDKN2A/2B gene in women with gestational diabetes. J Perinatol. 2017;37:345-348 pubmed publisher
    ..The results of this study suggest an association between CDKN2A/2B gene rs10811661 polymorphism and GDM. ..
  13. Burroughs A, Zhang D, Aravind L. The eukaryotic translation initiation regulator CDC123 defines a divergent clade of ATP-grasp enzymes with a predicted role in novel protein modifications. Biol Direct. 2015;10:21 pubmed publisher
  14. Kang E, Kim M, Kim C, Nam C, Han S, Hur K, et al. Association of common type 2 diabetes risk gene variants and posttransplantation diabetes mellitus in renal allograft recipients in Korea. Transplantation. 2009;88:693-8 pubmed publisher
    ..43, P =0.008), CDKN2A/B rs10811661 (OR=1.33, P =0.039), and KCNQ1 rs2237892 (OR=1.46, P =0.009). These data suggest that genetic variations in TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, and KCNQ1 are associated with PTDM in Korea. ..
  15. Simonis Bik A, Nijpels G, van Haeften T, Houwing Duistermaat J, Boomsma D, Reiling E, et al. Gene variants in the novel type 2 diabetes loci CDC123/CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B affect different aspects of pancreatic beta-cell function. Diabetes. 2010;59:293-301 pubmed publisher
    ..These findings point to a clear diversity in the impact that these various gene variants may have on (dys)function of pancreatic beta-cells. ..
  16. Hayashi Y, Tsujita R, Tsubota M, Saeki H, Sekiguchi F, Honda G, et al. Human soluble thrombomodulin-induced blockade of peripheral HMGB1-dependent allodynia in mice requires both the lectin-like and EGF-like domains. Biochem Biophys Res Commun. 2018;495:634-638 pubmed publisher
    ..We prepared TM's D123, D1 and D2 by the protein expression system of yeast, and evaluated their effects on HMGB1 degradation in vitro ..
  17. Zhou D, Liu Y, Zhang D, Liu S, Yu L, Yang Y, et al. Variations in/nearby genes coding for JAZF1, TSPAN8/LGR5 and HHEX-IDE and risk of type 2 diabetes in Han Chinese. J Hum Genet. 2010;55:810-5 pubmed publisher
    ..15(1.10-1.21); P=1.93 × 10(-8)). This large population-based study and meta-analysis further confirmed the modest effects of the JAZF1, TSPAN8/LGR5 and HHEX-IDE loci on type 2 diabetes in Chinese and other East Asians. ..
  18. Schleinitz D, Tonjes A, Bottcher Y, Dietrich K, Enigk B, Koriath M, et al. Lack of significant effects of the type 2 diabetes susceptibility loci JAZF1, CDC123/CAMK1D, NOTCH2, ADAMTS9, THADA, and TSPAN8/LGR5 on diabetes and quantitative metabolic traits. Horm Metab Res. 2010;42:14-22 pubmed publisher
    ..This is compatible with the modest effect size of these "second sweep" variants, which will require large-scale association studies on quantitative traits to clarify their role in the pathophysiology of T2D. ..
  19. Talmud P, Hingorani A, Cooper J, Marmot M, Brunner E, Kumari M, et al. Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study. BMJ. 2010;340:b4838 pubmed publisher
  20. Wen J, Rönn T, Olsson A, Yang Z, Lu B, Du Y, et al. Investigation of type 2 diabetes risk alleles support CDKN2A/B, CDKAL1, and TCF7L2 as susceptibility genes in a Han Chinese cohort. PLoS ONE. 2010;5:e9153 pubmed publisher
  21. Okuda A, Kimura G. An amino acid change in novel protein D123 is responsible for temperature-sensitive G1-phase arrest in a mutant of rat fibroblast line 3Y1. Exp Cell Res. 1996;223:242-9 pubmed
    ..Using a human cDNA expression library, we succeeded in the molecular cloning of a cDNA (designated as D123 cDNA) that functionally complemented the temperature-sensitive mutation...
  22. Zhao J, Bradfield J, Zhang H, Annaiah K, Wang K, Kim C, et al. Examination of all type 2 diabetes GWAS loci reveals HHEX-IDE as a locus influencing pediatric BMI. Diabetes. 2010;59:751-5 pubmed publisher
    ..Our data show that the same genetic HHEX-IDE variant, which is associated with type 2 diabetes from previous studies, also influences pediatric BMI. ..
  23. Lango Allen H, Johansson S, Ellard S, Shields B, Hertel J, Raeder H, et al. Polygenic risk variants for type 2 diabetes susceptibility modify age at diagnosis in monogenic HNF1A diabetes. Diabetes. 2010;59:266-71 pubmed publisher
    ..This is one of the first studies to demonstrate that clinical characteristics of a monogenic disease can be modified by common polygenic variants. ..
  24. Salanti G, Southam L, Altshuler D, Ardlie K, Barroso I, Boehnke M, et al. Underlying genetic models of inheritance in established type 2 diabetes associations. Am J Epidemiol. 2009;170:537-45 pubmed publisher
    ..Information on the genetic model of robustly replicated association signals derived from genome-wide association studies may be useful for predictive modeling and for designing biologic and functional experiments. ..
  25. Onisto M, Zeilante P, Scannapieco P, Pellati D, Pozza M, Caenazzo C, et al. Expression study on D123 gene product: evidence for high positivity in testis. Exp Cell Res. 1998;242:451-9 pubmed
    A novel 44-kDa gene product (D123) has been proposed as necessary for S-phase entry of the cell cycle: a point mutation resulted in a temperature-sensitive arrest in G1-phase...
  26. Li H, Gan W, Lu L, Dong X, Han X, Hu C, et al. A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans. Diabetes. 2013;62:291-8 pubmed publisher
    ..0169) but not with fasting glucose. Our findings not only provide new insights into the pathophysiology of T2D, but may also shed light on the ethnic differences in T2D susceptibility. ..
  27. Gamboa Meléndez M, Huerta Chagoya A, Moreno Macias H, Vázquez Cárdenas P, Ordonez Sanchez M, Rodriguez Guillen R, et al. Contribution of common genetic variation to the risk of type 2 diabetes in the Mexican Mestizo population. Diabetes. 2012;61:3314-21 pubmed publisher
    ..Lack of association for the rest of the variants may have resulted from insufficient power to detect smaller allele effects. ..
  28. Imamura M, Iwata M, Maegawa H, Watada H, Hirose H, Tanaka Y, et al. Genetic variants at CDC123/CAMK1D and SPRY2 are associated with susceptibility to type 2 diabetes in the Japanese population. Diabetologia. 2011;54:3071-7 pubmed publisher
  29. Schulze M, Weikert C, Pischon T, Bergmann M, Al Hasani H, Schleicher E, et al. Use of multiple metabolic and genetic markers to improve the prediction of type 2 diabetes: the EPIC-Potsdam Study. Diabetes Care. 2009;32:2116-9 pubmed publisher
    ..002). Twenty SNPs did not improve discrimination beyond these characteristics (P = 0.69). Metabolic markers, but not genotyping for 20 diabetogenic SNPs, improve discrimination of incident type 2 diabetes beyond lifestyle risk factors. ..