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Gene Review

EPHA4  -  EPH receptor A4

Homo sapiens

Synonyms: EK8, EPH-like kinase 8, Ephrin type-A receptor 4, HEK8, Hek8, ...
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Disease relevance of EPHA4

  • The total cost of the first year after suspected myocardial infarction were on average 5680 SEK higher in the rt-PA group [1].
  • SEK/TYRO1 expression was observed in 75% and 17% of cell lines from primary and metastastic melanomas, respectively [2].
  • A comparison between treating the same woman for osteoporosis and mild hypertension shows a cost per life-year gained of 220,000 SEK and 128,000 SEK respectively [3].
  • CONCLUSIONS: The total community-based costs for the open and laparoscopic operations for chronic GERD amounted to 74,608 and 40,289 SEK, respectively [4].
  • RESULTS: The economic burden of diabetes mellitus is estimated at 5746 MSEK (1US$ = 7.50 SEK) in Sweden in 1994 [5].

Psychiatry related information on EPHA4

  • The cost per life-year gained was SEK 4000 in an estimation based on the observed risk reduction and ranged between SEK 62,000 and SEK 163,000 in three estimations based on the risk factor changes [6].
  • RESULTS: Total annual costs were on average 172,000 SEK, ranging from 60,700 SEK in mild dementia to 375,000 SEK in severe dementia [7].
  • As hypothesized, a small but significant relationship was found between scores on extraversion and on the SEK Test (colored spatial test) [8].
  • Furthermore, the cost of service and care for pensioners of good mental health is about SEK 50,000 higher than for the group of mentally disabled (everything else being the same) [9].
  • The average labour cost of group living for elderly people suffering from senile dementia amounted to just over SEK 230,000 per patient and year, or SEK 639 per patient and day (24h), in 1992 prices [10].

High impact information on EPHA4

  • Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism [11].
  • Using a chick embryogenesis model, we now demonstrate the existence of a vitamin K1-dependent protein-tyrosine phosphorylation cascade involving c-Eyk, a member of the Tyro 12 family, and key intracellular proteins, including focal adhesion kinase (pp125FAK), paxillin, and pp60src [12].
  • This population was found to harbor transcripts of the Hek8 and Hek11 members of this gene family [13].
  • Subsequent analysis of expression of these genes in B cells representing various differentiation and ontogenic stages showed that the Hek8 transcript is constitutively present in all fetal and adult B-lineage cells, with high levels of expression in peripheral blood B cells [13].
  • The down-regulation of EPHA4 by small interfering RNA in PC cells lead to attenuation of PC cell viability [14].

Biological context of EPHA4


Anatomical context of EPHA4

  • Recombinant SEK was shown to stimulate human CD4(+) and CD8(+) T cells in a Vbeta-specific manner; T-cells bearing Vbeta 5.1, 5.2, and 6.7 were significantly stimulated to proliferate [18].
  • Regulation of Epha4 expression in paraxial and lateral plate mesoderm by ectoderm-derived signals [19].
  • The most extensive type of indirect cost was loss of production or leisure, which averaged 1,286 SEK (SD=1,830) for injuries to permanent teeth and 699 SEK (SD=1,239) for injuries to primary teeth [20].
  • Dental care costs for treatment in the mandible was SEK 35 550, for the maxilla SEK 45 380 and for both jaws SEK 74 230 [21].
  • The present study shows an incremental cost-effectiveness of 2043 SEK (8.54 SEK = 1 US dollar, December 1999) per averted decayed enamel and dentine missing and filled surface (DeMFS), of which treatment costs represent 1337 SEK using the unit cost for a nurse [22].

Associations of EPHA4 with chemical compounds

  • However, five year direct medical costs per patient when given omeprazole were still significantly lower than for those having ARS in Denmark, Norway, and Sweden (differences were DKK 8703 (US$1475), NOK 32 992 (US$ 5155), and SEK 13 036 (US$ 1946), respectively) [23].
  • Hunter-Bolton reagent was used for iodination of CRF and the chloramine-T method for Tyro-CRF [24].
  • How-ever, phosphorylation of p38MAPK was prevented by the tyro-sine kinase Syk inhibitor piceatannol [25].
  • The net cost per QALY gained for losartan was 4188 euros (37,813 SEK), which is well within common Swedish benchmark upper values (200-500,000 SEK) for accepted cost-effective interventions [26].
  • The annual savings per patient ranged from SEK 5517 to 6387 during the first 4 years of propentofylline treatment [27].

Analytical, diagnostic and therapeutic context of EPHA4

  • On the other hand, the cost for hospital stay amounted to 35,488 SEK in the open group but was only 25,571 SEK for those undergoing laparoscopy [4].
  • The costs of the operations were 18,363 SEK for laparoscopy and 12,856 SEK for conventional fundoplication [4].
  • Including propentofylline in the treatment strategy yielded net savings of SEK 0.8 billion, since the savings in the cost of patient care outweighed the drug acquisition costs [27].
  • The total costs were SEK 51,000 (3000-808,000) for patients with primary healing and SEK 344,000 (27,000-992,000) for healing with amputation [28].
  • RESULTS: Laparoscopic cholecystectomy resulted in cost savings per patient amounting to about 2,400 SEK (as of 31 August 1994, Pound = 11.90 SEK; $1 = 7.76 SEK) compared with open surgery [29].


  1. Cost-effectiveness of thrombolysis--a randomized study of intravenous rt-PA in suspected myocardial infarction. Levin, L.A., Jönsson, B. Eur. Heart J. (1992) [Pubmed]
  2. Loss of expression of receptor tyrosine kinase family genes PTK7 and SEK in metastatic melanoma. Easty, D.J., Mitchell, P.J., Patel, K., Flørenes, V.A., Spritz, R.A., Bennett, D.C. Int. J. Cancer (1997) [Pubmed]
  3. Cost-effectiveness of fracture prevention in established osteoporosis. Jönsson, B., Christiansen, C., Johnell, O., Hedbrandt, J. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. (1995) [Pubmed]
  4. Laparoscopic or open fundoplication? A complete cost analysis. Blomqvist, A.M., Lönroth, H., Dalenbäck, J., Lundell, L. Surgical endoscopy. (1998) [Pubmed]
  5. Diabetes: the cost of illness in Sweden. Henriksson, F., Jönsson, B. J. Intern. Med. (1998) [Pubmed]
  6. The cost-effectiveness of a cardiovascular multiple-risk-factor intervention programme in treated hypertensive men. Johannesson, M., Agewall, S., Hartford, M., Hedner, T., Fagerberg, B. J. Intern. Med. (1995) [Pubmed]
  7. Determinants of costs of care for patients with Alzheimer's disease. Jönsson, L., Eriksdotter Jönhagen, M., Kilander, L., Soininen, H., Hallikainen, M., Waldemar, G., Nygaard, H., Andreasen, N., Winblad, B., Wimo, A. International journal of geriatric psychiatry. (2006) [Pubmed]
  8. Extraversion-introversion and spatial intelligence. Dunn, A., Eliot, J. Perceptual and motor skills. (1993) [Pubmed]
  9. Home service costs: the Swedish experience. Svensson, M., Edebalk, P.G., Persson, U. Health policy (Amsterdam, Netherlands) (1991) [Pubmed]
  10. Group living for elderly patients with dementia--a cost analysis. Svensson, M., Edebalk, P.G., Persson, U. Health policy (Amsterdam, Netherlands) (1996) [Pubmed]
  11. Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism. Fu, W.Y., Chen, Y., Sahin, M., Zhao, X.S., Shi, L., Bikoff, J.B., Lai, K.O., Yung, W.H., Fu, A.K., Greenberg, M.E., Ip, N.Y. Nat. Neurosci. (2007) [Pubmed]
  12. A novel role for vitamin K1 in a tyrosine phosphorylation cascade during chick embryogenesis. Saxena, S.P., Fan, T., Li, M., Israels, E.D., Israels, L.G. J. Clin. Invest. (1997) [Pubmed]
  13. Regulated expression of the Eph-related receptor tyrosine kinase Hek11 in early human B lymphopoiesis. Aasheim, H.C., Terstappen, L.W., Logtenberg, T. Blood (1997) [Pubmed]
  14. Molecular features of the transition from prostatic intraepithelial neoplasia (PIN) to prostate cancer: genome-wide gene-expression profiles of prostate cancers and PINs. Ashida, S., Nakagawa, H., Katagiri, T., Furihata, M., Iiizumi, M., Anazawa, Y., Tsunoda, T., Takata, R., Kasahara, K., Miki, T., Fujioka, T., Shuin, T., Nakamura, Y. Cancer Res. (2004) [Pubmed]
  15. Cost-effectiveness of intracytoplasmic sperm injection in comparison with donor insemination. Granberg, M., Wikland, M., Hamberger, L. Acta obstetricia et gynecologica Scandinavica. (1996) [Pubmed]
  16. A cost analysis of participation via personal attendance versus telemedicine at a head and neck oncology multidisciplinary team meeting. Stalfors, J., Björholt, I., Westin, T. Journal of telemedicine and telecare. (2005) [Pubmed]
  17. EphA4 receptor, overexpressed in pancreatic ductal adenocarcinoma, promotes cancer cell growth. Iiizumi, M., Hosokawa, M., Takehara, A., Chung, S., Nakamura, T., Katagiri, T., Eguchi, H., Ohigashi, H., Ishikawa, O., Nakamura, Y., Nakagawa, H. Cancer Sci. (2006) [Pubmed]
  18. Biochemical and biological properties of Staphylococcal enterotoxin K. Orwin, P.M., Leung, D.Y., Donahue, H.L., Novick, R.P., Schlievert, P.M. Infect. Immun. (2001) [Pubmed]
  19. Regulation of Epha4 expression in paraxial and lateral plate mesoderm by ectoderm-derived signals. Schmidt, C., Christ, B., Maden, M., Brand-Saberi, B., Patel, K. Dev. Dyn. (2001) [Pubmed]
  20. Direct and indirect costs of dental trauma in Sweden: a 2-year prospective study of children and adolescents. Glendor, U., Jonsson, D., Halling, A., Lindqvist, K. Community dentistry and oral epidemiology. (2001) [Pubmed]
  21. Costs of periodontal and prosthodontic treatment and evaluation of oral health in patients after treatment of advanced periodontal disease. Karlsson, G., Teiwik, A., Lundström, A., Ravald, N. Community dentistry and oral epidemiology. (1995) [Pubmed]
  22. Cost-effectiveness of different caries preventive measures in a high-risk population of Swedish adolescents. Oscarson, N., Källestål, C., Fjelddahl, A., Lindholm, L. Community dentistry and oral epidemiology. (2003) [Pubmed]
  23. The cost of long term therapy for gastro-oesophageal reflux disease: a randomised trial comparing omeprazole and open antireflux surgery. Myrvold, H.E., Lundell, L., Miettinen, P., Pedersen, S.A., Liedman, B., Hatlebakk, J., Julkunen, R., Levander, K., Lamm, M., Mattson, C., Carlsson, J., Ståhlhammar, N.O. Gut (2001) [Pubmed]
  24. Metabolic clearance rate and plasma half-life of radioiodinated corticotropin releasing factor in a primate. Schulte, H.M., Chrousos, G.P., Gold, P.W., Oldfields, E.H., Phillips, J.M., Munson, P.J., Cutler, G.B., Loriaux, D.L. J. Clin. Endocrinol. Metab. (1982) [Pubmed]
  25. A role for p38 MAP kinase in platelet activation by von Willebrand factor. Canobbio, I., Reineri, S., Sinigaglia, F., Balduini, C., Torti, M. Thromb. Haemost. (2004) [Pubmed]
  26. Cost effectiveness of losartan in patients with hypertension and LVH: an economic evaluation for Sweden of the LIFE trial. Jönsson, B., Carides, G.W., Burke, T.A., Dasbach, E.J., Lindholm, L.H., Dahlöf, B. J. Hypertens. (2005) [Pubmed]
  27. Economic impact of introducing propentofylline for the treatment of dementia in Sweden. Wimo, A., Witthaus, E., Rother, M., Winblad, B. Clinical therapeutics. (1998) [Pubmed]
  28. Diabetic foot ulcers in a multidisciplinary setting. An economic analysis of primary healing and healing with amputation. Apelqvist, J., Ragnarson-Tennvall, G., Persson, U., Larsson, J. J. Intern. Med. (1994) [Pubmed]
  29. A cost-minimization analysis of laparoscopic cholecystectomy versus open cholecystectomy. Berggren, U., Zethraeus, N., Arvidsson, D., Haglund, U., Jonsson, B. Am. J. Surg. (1996) [Pubmed]
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