Gene Symbol: HHEX
Description: hematopoietically expressed homeobox
Alias: HEX, HMPH, HOX11L-PEN, PRH, PRHX, hematopoietically-expressed homeobox protein HHEX, homeobox protein HEX, homeobox protein PRH, homeobox, hematopoietically expressed, proline-rich homeodomain-containing transcription factor
Species: human
Products:     HHEX

Top Publications

  1. Topcu Z, Mack D, Hromas R, Borden K. The promyelocytic leukemia protein PML interacts with the proline-rich homeodomain protein PRH: a RING may link hematopoiesis and growth control. Oncogene. 1999;18:7091-100 pubmed
    ..2-hybrid techniques, we found that PML and a related RING protein, Z, bind the proline rich homeodomain protein (PRH) through their RING domains...
  2. Takeuchi F, Serizawa M, Yamamoto K, Fujisawa T, Nakashima E, Ohnaka K, et al. Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population. Diabetes. 2009;58:1690-9 pubmed publisher
    ..Moreover, significant associations were replicated in five other candidate loci: TCF7L2, IGF2BP2, SLC30A8, HHEX, and KCNJ11...
  3. Noy P, Williams H, Sawasdichai A, Gaston K, Jayaraman P. PRH/Hhex controls cell survival through coordinate transcriptional regulation of vascular endothelial growth factor signaling. Mol Cell Biol. 2010;30:2120-34 pubmed publisher
    The proline-rich homeodomain protein (PRH) plays multiple roles in the control of gene expression during embryonic development and in the adult...
  4. Kifagi C, Makni K, Boudawara M, Mnif F, Hamza N, Abid M, et al. Association of genetic variations in TCF7L2, SLC30A8, HHEX, LOC387761, and EXT2 with Type 2 diabetes mellitus in Tunisia. Genet Test Mol Biomarkers. 2011;15:399-405 pubmed publisher
    In recent genome-wide association studies, genetic variants in TCF7L2, SLC30A8, HHEX, LOC387761, and EXT2 were associated with risk for type 2 diabetes mellitus (T2DM)...
  5. George A, Morse H, Justice M. The homeobox gene Hex induces T-cell-derived lymphomas when overexpressed in hematopoietic precursor cells. Oncogene. 2003;22:6764-73 pubmed
    ..in B- and T-cell leukemias and lymphomas in AKXD mice and activate two nearby genes, the divergent homeobox gene Hex and the kinesin-related spindle protein gene Eg5...
  6. van Vliet Ostaptchouk J, Onland Moret N, van Haeften T, Franke L, Elbers C, Shiri Sverdlov R, et al. HHEX gene polymorphisms are associated with type 2 diabetes in the Dutch Breda cohort. Eur J Hum Genet. 2008;16:652-6 pubmed publisher
    Recently, the hematopoietically expressed homeobox (HHEX) gene, encoding a transcription factor, was identified in a large genome-wide scan in French individuals as a type 2 diabetes (T2D)-susceptibility locus...
  7. Bedford F, Ashworth A, Enver T, Wiedemann L. HEX: a novel homeobox gene expressed during haematopoiesis and conserved between mouse and human. Nucleic Acids Res. 1993;21:1245-9 pubmed
    ..The human cDNA was initially isolated from human haematopoietic tissue and denoted HEX (haematopoietically expressed homeobox)...
  8. Staiger H, Machicao F, Stefan N, Tschritter O, Thamer C, Kantartzis K, et al. Polymorphisms within novel risk loci for type 2 diabetes determine beta-cell function. PLoS ONE. 2007;2:e832 pubmed
    ..Very recently, genetic variations within four novel genetic loci (SLC30A8, HHEX, EXT2, and LOC387761) were reported to be more frequent in subjects with type 2 diabetes than in healthy controls...
  9. Cornelis M, Qi L, Zhang C, Kraft P, Manson J, Cai T, et al. Joint effects of common genetic variants on the risk for type 2 diabetes in U.S. men and women of European ancestry. Ann Intern Med. 2009;150:541-50 pubmed
    ..National Institutes of Health. ..

More Information


  1. Rong R, Hanson R, Ortiz D, Wiedrich C, Kobes S, Knowler W, et al. Association analysis of variation in/near FTO, CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, LOC387761, and CDKN2B with type 2 diabetes and related quantitative traits in Pima Indians. Diabetes. 2009;58:478-88 pubmed publisher
    In recent genome-wide association studies, variants in CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, CDKN2B, LOC387761, and FTO were associated with risk for type 2 diabetes in Caucasians...
  2. Cauchi S, Proenca C, Choquet H, Gaget S, De Graeve F, Marre M, et al. Analysis of novel risk loci for type 2 diabetes in a general French population: the D.E.S.I.R. study. J Mol Med (Berl). 2008;86:341-8 pubmed publisher
    ..showing nominal to strong association with T2D in recently published GWA analyses (CDKAL1, IGFBP2, CDKN2A/2B, EXT2, HHEX, LOC646279, SLC30A8, MMP26, KCTD12, LDLR, CAMTA1, LOC38776, NGN3 and CXCR4)...
  3. Hromas R, Radich J, Collins S. PCR cloning of an orphan homeobox gene (PRH) preferentially expressed in myeloid and liver cells. Biochem Biophys Res Commun. 1993;195:976-83 pubmed
    ..polymerase chain reaction (PCR), we cloned from the HL60 promyelocytic cell line a homeobox gene we now designate PRH. We mapped this gene, which was not homologous to any of the previously described homeobox genes, to chromosome 10, ..
  4. Han X, Luo Y, Ren Q, Zhang X, Wang F, Sun X, et al. Implication of genetic variants near SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, FTO, TCF2, KCNQ1, and WFS1 in type 2 diabetes in a Chinese population. BMC Med Genet. 2010;11:81 pubmed publisher
    ..many novel genetic loci for type 2 diabetes (T2D); among these genes, CDKAL1, IGF2BP2, SLC30A8, CDKN2A/B, HHEX, FTO, TCF2, KCNQ1, and WFS1 are the most important...
  5. Zeggini E, Weedon M, Lindgren C, Frayling T, Elliott K, Lango H, et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007;316:1336-41 pubmed
    ..in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8...
  6. Minami T, Murakami T, Horiuchi K, Miura M, Noguchi T, Miyazaki J, et al. Interaction between hex and GATA transcription factors in vascular endothelial cells inhibits flk-1/KDR-mediated vascular endothelial growth factor signaling. J Biol Chem. 2004;279:20626-35 pubmed
    ..Using yeast two-hybrid screening, we identified hematopoietically expressed homeobox (Hex) as a GATA-binding partner in endothelial cells...
  7. Hertel J, Johansson S, Raeder H, Midthjell K, Lyssenko V, Groop L, et al. Genetic analysis of recently identified type 2 diabetes loci in 1,638 unselected patients with type 2 diabetes and 1,858 control participants from a Norwegian population-based cohort (the HUNT study). Diabetologia. 2008;51:971-7 pubmed publisher
    ..single nucleotide polymorphisms (SNPs) in PKN2, IGFBP2, FLJ39370 (also known as C4ORF32), CDKAL1, SLC30A8, CDKN2B, HHEX and FTO using a Norwegian population-based sample of 1,638 patients with type 2 diabetes and 1,858 non-diabetic ..
  8. Freathy R, Bennett A, Ring S, Shields B, Groves C, Timpson N, et al. Type 2 diabetes risk alleles are associated with reduced size at birth. Diabetes. 2009;58:1428-33 pubmed publisher
    ..single-nucleotide polymorphisms (SNPs) at five recently identified type 2 diabetes loci (CDKAL1, CDKN2A/B, HHEX-IDE, IGF2BP2, and SLC30A8) in 7,986 mothers and 19,200 offspring from four studies of white Europeans...
  9. Lee Y, Kang E, Kim S, Han S, Kim C, Kim H, et al. Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population. J Hum Genet. 2008;53:991-8 pubmed publisher
    ..The aim of the present study was to investigate the association among the polymorphisms of SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1 and KCNQ1 and the risk of T2DM in the Korean population...
  10. Williams H, Jayaraman P, Gaston K. DNA wrapping and distortion by an oligomeric homeodomain protein. J Mol Biol. 2008;383:10-23 pubmed publisher
    ..The proline-rich homeodomain (PRH/Hex) protein is a transcription factor that regulates cell differentiation and cell proliferation, and has multiple ..
  11. Jankovic D, Gorello P, Liu T, Ehret S, La Starza R, Desjobert C, et al. Leukemogenic mechanisms and targets of a NUP98/HHEX fusion in acute myeloid leukemia. Blood. 2008;111:5672-82 pubmed publisher
    ..involving nucleoporin 98 (NUP98) fused to the DNA-binding domain of the hematopoietically expressed homeobox gene (HHEX)...
  12. Horikoshi M, Hara K, Ito C, Shojima N, Nagai R, Ueki K, et al. Variations in the HHEX gene are associated with increased risk of type 2 diabetes in the Japanese population. Diabetologia. 2007;50:2461-6 pubmed
    ..FTO), solute carrier family 30 (zinc transporter), member 8 (SLC30A8), haematopoietically expressed homeobox (HHEX), exostoses (multiple) 2 (EXT2), CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1), cyclin-dependent ..
  13. D Elia A, Tell G, Russo D, Arturi F, Puglisi F, Manfioletti G, et al. Expression and localization of the homeodomain-containing protein HEX in human thyroid tumors. J Clin Endocrinol Metab. 2002;87:1376-83 pubmed
    ..The divergent homeobox gene HEX is expressed in the anterior visceral endoderm during early mouse development and in some adult tissues of ..
  14. Groenewoud M, Dekker J, Fritsche A, Reiling E, Nijpels G, Heine R, et al. Variants of CDKAL1 and IGF2BP2 affect first-phase insulin secretion during hyperglycaemic clamps. Diabetologia. 2008;51:1659-63 pubmed publisher
    ..Variants of the HHEX/IDE, CDKAL1, SLC30A8, IGF2BP2 and CDKN2A/CDKN2B genes were genotyped in a cohort of 146 participants with NGT and ..
  15. Zhao J, Li M, Bradfield J, Wang K, Zhang H, Sleiman P, et al. Examination of type 2 diabetes loci implicates CDKAL1 as a birth weight gene. Diabetes. 2009;58:2414-8 pubmed publisher
    ..has been demonstrated between low birth weight and single nucleotide polymorphisms (SNPs) at the CDKAL1 and HHEX-IDE loci, regions that were previously implicated in the pathogenesis of type 2 diabetes...
  16. 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. ..
  17. Manfioletti G, Gattei V, Buratti E, Rustighi A, De Iuliis A, Aldinucci D, et al. Differential expression of a novel proline-rich homeobox gene (Prh) in human hematolymphopoietic cells. Blood. 1995;85:1237-45 pubmed
    Proline-rich homeobox (Prh) is a novel human homeobox-containing gene recently isolated from the CD34+ cell line KG-1A, and whose expression appears mainly restricted to hematopoietic tissues...
  18. Furukawa Y, Shimada T, Furuta H, Matsuno S, Kusuyama A, Doi A, et al. Polymorphisms in the IDE-KIF11-HHEX gene locus are reproducibly associated with type 2 diabetes in a Japanese population. J Clin Endocrinol Metab. 2008;93:310-4 pubmed
    ..study in the French population has detected that novel single-nucleotide polymorphisms (SNPs) in the IDE-KIF11-HHEX gene locus and the SLC30A8 gene locus are associated with susceptibility to type 2 diabetes...
  19. Pascoe L, Tura A, Patel S, Ibrahim I, Ferrannini E, Zeggini E, et al. Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic beta-cell function. Diabetes. 2007;56:3101-4 pubmed
    ..have identified common, novel type 2 diabetes susceptibility loci within the FTO, CDKAL1, CDKN2A/CDKN2B, IGF2BP2, HHEX/IDE, and SLC30A8 gene regions...
  20. Pascoe L, Frayling T, Weedon M, Mari A, Tura A, Ferrannini E, et al. Beta cell glucose sensitivity is decreased by 39% in non-diabetic individuals carrying multiple diabetes-risk alleles compared with those with no risk alleles. Diabetologia. 2008;51:1989-92 pubmed publisher
    ..Initial analysis focused on CDKAL1, HHEX/IDE and TCF7L2 loci, which were individually associated with a decrease in beta cell function in our cohort...
  21. Wang Y, Qiao W, Zhao X, Tao M. Quantitative assessment of the influence of hematopoietically expressed homeobox variant (rs1111875) on type 2 diabetes risk. Mol Genet Metab. 2011;102:194-9 pubmed publisher
    Hematopoietically expressed homeobox (HHEX) gene encodes for a transcription factor involved in Wnt/?-catenin signaling pathway which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D) since it was first ..
  22. Saxena R, Voight B, Lyssenko V, Burtt N, de Bakker P, Chen H, et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science. 2007;316:1331-6 pubmed
    ..region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1-and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study...
  23. Moore A, Jablonski K, McAteer J, Saxena R, Pollin T, Franks P, et al. Extension of type 2 diabetes genome-wide association scan results in the diabetes prevention program. Diabetes. 2008;57:2503-10 pubmed publisher
  24. Puppin C, Puglisi F, Pellizzari L, Manfioletti G, Pestrin M, Pandolfi M, et al. HEX expression and localization in normal mammary gland and breast carcinoma. BMC Cancer. 2006;6:192 pubmed
    The homeobox gene HEX is expressed in several cell types during different phases of animal development. It encodes for a protein localized in both the nucleus and the cytoplasm...
  25. Cho Y, Kim T, Lim S, Choi S, Shin H, Lee H, et al. Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population. Diabetologia. 2009;52:253-61 pubmed publisher
    ..rs10757278 and rs10811661 in the CDKN2A-CDKN2B region; rs8050136 in FTO; rs1111875, rs5015480 and rs7923837 in HHEX; rs4402960 in IGF2BP2; and rs13266634 in SLC30A8...
  26. Morgutti M, Demori E, Pecile V, Amoroso A, Rustighi A, Manfioletti G. Genomic organization and chromosome mapping of the human homeobox gene HHEX. Cytogenet Cell Genet. 2001;94:30-2 pubmed
    In the present study, we report the genomic reconstruction of the human homeobox-containing gene HHEX by the use of the data available in public databases...
  27. Cai Y, Yi J, Ma Y, Fu D. Meta-analysis of the effect of HHEX gene polymorphism on the risk of type 2 diabetes. Mutagenesis. 2011;26:309-14 pubmed publisher
    ..the past decade, a number of case-control studies have been carried out to investigate the relationship between the HHEX polymorphism and type 2 diabetes (T2D). However, the results have been inconclusive...
  28. Ruchat S, Rankinen T, Weisnagel S, Rice T, Rao D, Bergman R, et al. Improvements in glucose homeostasis in response to regular exercise are influenced by the PPARG Pro12Ala variant: results from the HERITAGE Family Study. Diabetologia. 2010;53:679-89 pubmed publisher
    ..eight polymorphisms in seven type 2 diabetes genes (CDKAL1 rs7756992; CDKN2A and CDKN2B rs10811661 and rs564398; HHEX rs7923837; IGF2BP2 rs4402960; KCNJ11 rs5215; PPARG rs1801282; and TCF7L2 rs7903146) in a maximum of 481 sedentary, ..
  29. Tabara Y, Osawa H, Kawamoto R, Onuma H, Shimizu I, Miki T, et al. Replication study of candidate genes associated with type 2 diabetes based on genome-wide screening. Diabetes. 2009;58:493-8 pubmed publisher
    ..A total of 11 previously reported single-nucleotide polymorphisms (SNPs) from the TCF7L2, CDKAL1, HHEX, IGF2BP2, CDKN2A/B, SLC30A8, and KCNJ11 genes were analyzed...
  30. 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
    ..18 type 2 diabetes loci uncovered through GWAS, consisting of ADAMTS9, CDC123-CAMK1D, CDKAL1, CDKN2A/B, EXT2, FTO, HHEX-IDE, IGF2BP2, the intragenic region on 11p12, JAZF1, KCNQ1, LOC387761, MTNR1B, NOTCH2, SLC30A8, TCF7L2, THADA, and ..
  31. Chidambaram M, Radha V, Mohan V. Replication of recently described type 2 diabetes gene variants in a South Indian population. Metabolism. 2010;59:1760-6 pubmed publisher
    ..029)-of the CDKAL1, rs7020996 (P = .003) of the CDKN2A/B gene, rs7923837 (P = .038) of the HHEX gene, and rs12056034 (P = .033) of the BAZ1B gene were associated with T2D in our population...
  32. Winkler C, Illig T, Koczwara K, Bonifacio E, Ziegler A. HHEX-IDE polymorphism is associated with low birth weight in offspring with a family history of type 1 diabetes. J Clin Endocrinol Metab. 2009;94:4113-5 pubmed publisher
    ..also reduce birth weight, and an association of low birth weight and the type 2 diabetes risk alleles at the HHEX-IDE and CDKAL1 loci were recently reported...
  33. Pulizzi N, Lyssenko V, Jonsson A, Osmond C, Laakso M, Kajantie E, et al. Interaction between prenatal growth and high-risk genotypes in the development of type 2 diabetes. Diabetologia. 2009;52:825-9 pubmed publisher
    ..study was to investigate whether there is an interaction between birthweight and common variants in the TCF7L2, HHEX, PPARG, KCNJ11, SLC30A8, IGF2BP2, CDKAL1, CDKN2A/2B and JAZF1 genes in the risk of developing type 2 diabetes...
  34. Desjobert C, Noy P, Swingler T, Williams H, Gaston K, Jayaraman P. The PRH/Hex repressor protein causes nuclear retention of Groucho/TLE co-repressors. Biochem J. 2009;417:121-32 pubmed publisher
    The PRH (proline-rich homeodomain) [also known as Hex (haematopoietically expressed homeobox)] protein is a transcription factor that functions as an important regulator of vertebrate development and many other processes in the adult ..
  35. Haupt A, Staiger H, Schafer S, Kirchhoff K, Guthoff M, Machicao F, et al. The risk allele load accelerates the age-dependent decline in beta cell function. Diabetologia. 2009;52:457-62 pubmed publisher
    Among the novel type 2 diabetes risk loci identified by genome-wide association studies, TCF7L2, HHEX, SLC30A8 and CDKAL1 appear to affect beta cell function...
  36. Bess K, Swingler T, Rivett A, Gaston K, Jayaraman P. The transcriptional repressor protein PRH interacts with the proteasome. Biochem J. 2003;374:667-75 pubmed
    b>PRH (proline-rich homeodomain protein)/Hex is important in the control of cell proliferation and differentiation...
  37. Grarup N, Rose C, Andersson E, Andersen G, Nielsen A, Albrechtsen A, et al. Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects: validation and extension of genome-wide association studies. Diabetes. 2007;56:3105-11 pubmed publisher
    ..validate the type 2 diabetes susceptibility alleles identified in six recent genome-wide association studies in the HHEX/KIF11/IDE (rs1111875), CDKN2A/B (rs10811661), and IGF2BP2 (rs4402960) loci, as well as the intergenic rs9300039 ..
  38. Schulze M, Al Hasani H, Boeing H, Fisher E, Doring F, Joost H. Variation in the HHEX-IDE gene region predisposes to type 2 diabetes in the prospective, population-based EPIC-Potsdam cohort. Diabetologia. 2007;50:2405-7 pubmed
  39. Cauchi S, Meyre D, Durand E, Proenca C, Marre M, Hadjadj S, et al. Post genome-wide association studies of novel genes associated with type 2 diabetes show gene-gene interaction and high predictive value. PLoS ONE. 2008;3:e2031 pubmed publisher
    ..of French subjects (4,232 T2D and 4,595 NGT), IGFBP2 and CXCR4 synergistically interacted with (LOC38776, SLC30A8, HHEX) and (NGN3, CDKN2A/2B), respectively, encoding for proteins presumably regulating pancreatic endocrine cell ..
  40. 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
    Several genetic loci (JAZF1, CDC123/CAMK1D, TSPAN8/LGR5, ADAMTS9, VEGFA and HHEX-IDE) were identified to be significantly related to the risk of type 2 diabetes and quantitative metabolic traits in European populations...
  41. Ruchat S, Elks C, Loos R, Vohl M, Weisnagel S, Rankinen T, et al. Association between insulin secretion, insulin sensitivity and type 2 diabetes susceptibility variants identified in genome-wide association studies. Acta Diabetol. 2009;46:217-26 pubmed publisher
    ..We analysed 23 SNPs in 9 T2DM genes (CDKAL1, CDKN2B, HHEX/IDE, IGF2BP2, KCNJ11, SLC30A8, TCF2, TCF7L2 and WFS1) in a maximum of 712 men and women from the Quebec Family ..
  42. Cruz M, Valladares Salgado A, Garcia Mena J, Ross K, Edwards M, Angeles Martinez J, et al. Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City. Diabetes Metab Res Rev. 2010;26:261-70 pubmed publisher
    ..of 14 polymorphisms located within 10 genes (TCF7L2, ENPP1, ADRB3, KCNJ11, LEPR, PPARgamma, FTO, CDKAL1, SIRT1 and HHEX) with T2D and MS...
  43. Schaefer L, Wang S, Schaefer T. Functional interaction of Jun and homeodomain proteins. J Biol Chem. 2001;276:43074-82 pubmed
    ..One of the proteins identified is the homeodomain-containing protein Hex. The Hex homeodomain is sufficient for interaction; moreover, the homeodomains of several other transcription ..
  44. Gupta V, Khadgawat R, Ng H, Kumar S, Aggarwal A, Rao V, et al. A validation study of type 2 diabetes-related variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ genes in one endogamous ethnic group of north India. Ann Hum Genet. 2010;74:361-8 pubmed publisher
    The aim of this study was to validate the single nucleotide polymorphisms (SNPs) of four candidate genes (TCF7L2, HHEX, KCNJ11, and ADIPOQ) related to type 2 diabetes (T2D) in an endogamous population of north India; the Aggarwal ..
  45. Omori S, Tanaka Y, Takahashi A, Hirose H, Kashiwagi A, Kaku K, et al. Association of CDKAL1, IGF2BP2, CDKN2A/B, HHEX, SLC30A8, and KCNJ11 with susceptibility to type 2 diabetes in a Japanese population. Diabetes. 2008;57:791-5 pubmed
    ..We analyzed 14 SNPs (rs4402960 in IGF2BP2, rs10811661 in CDKN2A/B, rs1111875 and rs7923837 in HHEX, rs13266634 in SLC30A8, rs1113132 and rs11037909 in EXT2, rs9939609 and rs8050136 in FTO, rs7756992 in CDKAL1, ..
  46. Crompton M, Bartlett T, MacGregor A, Manfioletti G, Buratti E, Giancotti V, et al. Identification of a novel vertebrate homeobox gene expressed in haematopoietic cells. Nucleic Acids Res. 1992;20:5661-7 pubmed
    This paper describes the characterisation of a novel chicken homeobox gene, Prh, whose encoded homeodomain sequence differs significantly from those of other factors which have been described...
  47. Sanghera D, Ortega L, Han S, Singh J, Ralhan S, Wander G, et al. Impact of nine common type 2 diabetes risk polymorphisms in Asian Indian Sikhs: PPARG2 (Pro12Ala), IGF2BP2, TCF7L2 and FTO variants confer a significant risk. BMC Med Genet. 2008;9:59 pubmed publisher
    ..variant found near cyclin-dependent kinase inhibitor 2A (CDKN2A; rs10811661); hematopoietically expressed homeobox (HHEX; rs 1111875); transcription factor-7-like 2 (TCF7L2; rs 10885409); potassium inwardly rectifying channel subfamily ..
  48. Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007;445:881-5 pubmed
    ..disequilibrium blocks that contain genes potentially involved in beta-cell development or function (IDE-KIF11-HHEX and EXT2-ALX4)...
  49. Ng M, Park K, Oh B, Tam C, Cho Y, Shin H, et al. Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians. Diabetes. 2008;57:2226-33 pubmed publisher
    ..We confirmed the associations of TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/CDKN2B, IGF2BP2, and FTO with risk for type 2 diabetes, with odds ratios ranging from 1.13 to 1...
  50. Horikawa Y, Miyake K, Yasuda K, Enya M, Hirota Y, Yamagata K, et al. Replication of genome-wide association studies of type 2 diabetes susceptibility in Japan. J Clin Endocrinol Metab. 2008;93:3136-41 pubmed publisher
    ..origin, several groups have recently identified novel type 2 diabetes susceptibility genes, including FTO, SLC30A8, HHEX, CDKAL1, CDKN2B, and IGF2BP2, none of which were in the list of functional candidates...
  51. Swingler T, Bess K, Yao J, Stifani S, Jayaraman P. The proline-rich homeodomain protein recruits members of the Groucho/Transducin-like enhancer of split protein family to co-repress transcription in hematopoietic cells. J Biol Chem. 2004;279:34938-47 pubmed
    The proline-rich homeodomain protein (PRH/Hex) is important in the control of cell proliferation and differentiation and in the regulation of multiple processes in embryonic development...
  52. Ryoo H, Woo J, Kim Y, Lee C. Heterogeneity of genetic associations of CDKAL1 and HHEX with susceptibility of type 2 diabetes mellitus by gender. Eur J Hum Genet. 2011;19:672-5 pubmed publisher
    ..0015). One was located near the gene of hematopoietically expressed homeobox (HHEX), and the others were all in the gene of cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (..
  53. van Hoek M, Langendonk J, de Rooij S, Sijbrands E, Roseboom T. Genetic variant in the IGF2BP2 gene may interact with fetal malnutrition to affect glucose metabolism. Diabetes. 2009;58:1440-4 pubmed publisher
    ..The rs7754840 (CDKAL1), rs10811661 (CDKN2AB), rs1111875 (HHEX), rs4402960 (IGF2BP2), rs5219 (KCNJ11), rs13266634 (SLC30A8), and rs7903146 (TCF7L2) polymorphisms were genotyped ..
  54. 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. ..
  55. Topisirovic I, Culjkovic B, Cohen N, Perez J, Skrabanek L, Borden K. The proline-rich homeodomain protein, PRH, is a tissue-specific inhibitor of eIF4E-dependent cyclin D1 mRNA transport and growth. EMBO J. 2003;22:689-703 pubmed
    ..Surprisingly, we found that a trans cription factor, the proline-rich homeodomain protein PRH, is a negative regulator of eIF4E in myeloid cells, interacting with eIF4E through a conserved binding site ..
  56. 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
    ..Oral glucose tolerance tests and genotyping of SNPs in or near PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, LOC387761, CDKN2B, IGF2BP2, CDKAL1, HNF1B, WFS1, JAZF1, CDC123, TSPAN8, THADA, ADAMTS9, NOTCH2, KCNQ1, and MTNR1B ..
  57. Wu Y, Li H, Loos R, Yu Z, Ye X, Chen L, et al. Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population. Diabetes. 2008;57:2834-42 pubmed publisher
    Genome-wide association studies have identified common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, HHEX/IDE, EXT2, and LOC387761 loci that significantly increase the risk of type 2 diabetes...
  58. Hu C, Zhang R, Wang C, Wang J, Ma X, Lu J, et al. PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population. PLoS ONE. 2009;4:e7643 pubmed publisher
    ..We confirmed the effects of SNPs from PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 on risk for type 2 diabetes, with odds ratios ranging from 1.114 to 1...
  59. Chauhan G, Spurgeon C, Tabassum R, Bhaskar S, Kulkarni S, Mahajan A, et al. Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians. Diabetes. 2010;59:2068-74 pubmed publisher
    Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 genes have been shown to be associated with type 2 diabetes in European populations by genome-wide association studies...
  60. Staiger H, Stancakova A, Zilinskaite J, Vänttinen M, Hansen T, Marini M, et al. A candidate type 2 diabetes polymorphism near the HHEX locus affects acute glucose-stimulated insulin release in European populations: results from the EUGENE2 study. Diabetes. 2008;57:514-7 pubmed
    In recent genome-wide association studies, two single nucleotide polymorphisms (SNPs) near the HHEX locus were shown to be more frequent in type 2 diabetic patients than in control subjects...
  61. Scott L, Mohlke K, Bonnycastle L, Willer C, Li Y, Duren W, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science. 2007;316:1341-5 pubmed
    ..the genes IGF2BP2 and CDKAL1 and the region of CDKN2A and CDKN2B, and confirm that variants near TCF7L2, SLC30A8, HHEX, FTO, PPARG, and KCNJ11 are associated with T2D risk...
  62. Lin Y, Li P, Cai L, Zhang B, Tang X, Zhang X, et al. Association study of genetic variants in eight genes/loci with type 2 diabetes in a Han Chinese population. BMC Med Genet. 2010;11:97 pubmed publisher
    ..Nineteen single nucleotide polymorphisms (SNPs) from the eight genes/loci including TCF7L2, HHEX, CDKAL1, SLC30A8, PPARG, IGF2BP2, KCNJ11, and CDKN2A/CDKN2B were genotyped in 1,529 cases and 1,439 controls in a ..
  63. Herder C, Rathmann W, Strassburger K, Finner H, Grallert H, Huth C, et al. Variants of the PPARG, IGF2BP2, CDKAL1, HHEX, and TCF7L2 genes confer risk of type 2 diabetes independently of BMI in the German KORA studies. Horm Metab Res. 2008;40:722-6 pubmed publisher
    ..39, p-values 0.0008-0.0004]. In addition, we found evidence for association of SNPs in the genes PPARG, IGF2BP2, HHEX, TCF7L2, and FTO with type 2 diabetes in the same directions as previously described (p<0...
  64. 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. ..
  65. 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
    ..Variants in 11 genes (TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX) were significantly associated with the risk of type 2 diabetes independently of clinical risk factors; variants in ..
  66. 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. ..
  67. Pivovarova O, Nikiforova V, Pfeiffer A, Rudovich N. The influence of genetic variations in HHEX gene on insulin metabolism in the German MESYBEPO cohort. Diabetes Metab Res Rev. 2009;25:156-62 pubmed publisher
    ..alleles identified in the first genome-wide association study in the hematopoietically expressed homeobox protein (HHEX) gene region (rs1111875 and rs7923837)...
  68. Lauenborg J, Grarup N, Damm P, Borch Johnsen K, Jørgensen T, Pedersen O, et al. Common type 2 diabetes risk gene variants associate with gestational diabetes. J Clin Endocrinol Metab. 2009;94:145-50 pubmed publisher
    ..Type 2 diabetes risk variants in TCF7L2, CDKAL1, SLC30A8, HHEX/IDE, CDKN2A/2B, IGF2BP2, FTO, TCF2, PPARG, KCNJ11, and WFS1 loci were genotyped in a cohort of women with a history ..
  69. Soufi A, Noy P, Buckle M, Sawasdichai A, Gaston K, Jayaraman P. CK2 phosphorylation of the PRH/Hex homeodomain functions as a reversible switch for DNA binding. Nucleic Acids Res. 2009;37:3288-300 pubmed publisher
    The proline-rich homeodomain protein (PRH/Hex) regulates transcription by binding to specific DNA sequences and regulates mRNA transport by binding to translation initiation factor eIF4E...
  70. Tan J, Ng D, Nurbaya S, Ye S, Lim X, Leong H, et al. Polymorphisms identified through genome-wide association studies and their associations with type 2 diabetes in Chinese, Malays, and Asian-Indians in Singapore. J Clin Endocrinol Metab. 2010;95:390-7 pubmed publisher
    ..To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore...
  71. Haupt A, Guthoff M, Schäfer S, Kirchhoff K, Machicao F, Gallwitz B, et al. The inhibitory effect of recent type 2 diabetes risk loci on insulin secretion is modulated by insulin sensitivity. J Clin Endocrinol Metab. 2009;94:1775-80 pubmed publisher
    ..We assessed whether the risk alleles in TCF7L2, CDKAL1, HHEX, SLC30A8, IGF2BP2, CDKN2A/2B, JAZF1, and WFS1 reduce insulin secretion in an additive manner and whether their ..
  72. Soufi A, Smith C, Clarke A, Gaston K, Jayaraman P. Oligomerisation of the developmental regulator proline rich homeodomain (PRH/Hex) is mediated by a novel proline-rich dimerisation domain. J Mol Biol. 2006;358:943-62 pubmed
    ..The Proline Rich Homeodomain protein (PRH/Hex) is a transcription factor and an essential regulator of embryonic development and haematopoiesis...
  73. Pellizzari L, D Elia A, Rustighi A, Manfioletti G, Tell G, Damante G. Expression and function of the homeodomain-containing protein Hex in thyroid cells. Nucleic Acids Res. 2000;28:2503-11 pubmed publisher
    The homeodomain-containing protein Hex (also named Prh) is expressed in primitive endoderm (during the early phases of development), in some endoderm-derived tissues and in endothelial and hematopoietic precursors...
  74. Nakagawa T, Abe M, Yamazaki T, Miyashita H, Niwa H, Kokubun S, et al. HEX acts as a negative regulator of angiogenesis by modulating the expression of angiogenesis-related gene in endothelial cells in vitro. Arterioscler Thromb Vasc Biol. 2003;23:231-7 pubmed
    The hematopoietically expressed homeobox (HEX) is transiently expressed in endothelial cells (ECs) during vascular formation in embryo. Here, we investigated whether HEX played any role in angiogenesis-related properties of ECs in vitro...