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Gene Review

LHX4  -  LIM homeobox 4

Homo sapiens

Synonyms: Gsh4, LIM homeobox protein 4, LIM/homeobox protein Lhx4
 
 
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Disease relevance of LHX4

 

Psychiatry related information on LHX4

  • Pathophysiology of syndromic combined pituitary hormone deficiency due to a LHX3 defect in light of LHX3 and LHX4 expression during early human development [5].
 

High impact information on LHX4

  • LHX4, which encodes a protein 99% identical to its murine counterpart, consists of six coding exons and spans >45 kb of the q25 region of chromosome 1 [6].
  • We report a family with an LHX4 germline splice-site mutation that results in a disease phenotype characterized by short stature and by pituitary and hindbrain (i.e., cerebellar) defects in combination with abnormalities of the sella turcica of the central skull base [6].
  • Deficiencies in the homeobox transcription factors LHX4 and PROP1 cause pituitary hormone deficiency in both humans and mice [7].
  • We demonstrate that SLB specifically binds to Lhx3 and Lhx4 with high affinity both in vitro and in vivo [8].
  • As shown in this cell system, the mutant LHX4 proteins predicted by the defect identified in patients fail to bind to and subsequently activate the POU1F1 regulatory sequence, but do not impair the ability of normal LHX4 to activate this target [9].
 

Biological context of LHX4

 

Anatomical context of LHX4

 

Associations of LHX4 with chemical compounds

  • To this end, we isolated Bacterial Artificial Chromosome clones for the canine LHX4 gene [3].
 

Other interactions of LHX4

  • However, whereas LHX3 is expressed at all stages studied, LHX4 expression is transient, and, at 6 weeks of development, is stronger at the caudal than at the cervical level [5].
  • More recently mutations in the HESX1, the LHX3 and LHX4 transcription factor genes have also been described as a cause in patients with CPHD [11].
  • cDNA cloning, chromosomal localization and expression pattern analysis of human LIM-homeobox gene LHX4 [10].
  • Human MTE Array was used to study the expression profile of LHX4 in 72 human tissues [10].

References

  1. Aberrant expression of the LHX4 LIM-homeobox gene caused by t(1;14)(q25;q32) in chronic myelogenous leukemia in biphenotypic blast crisis. Yamaguchi, M., Yamamoto, K., Miura, O. Genes Chromosomes Cancer (2003) [Pubmed]
  2. Hormonal, pituitary magnetic resonance, LHX4 and HESX1 evaluation in patients with hypopituitarism and ectopic posterior pituitary lobe. Melo, M.E., Marui, S., Carvalho, L.R., Arnhold, I.J., Leite, C.C., Mendon??a, B.B., Knoepfelmacher, M. Clin. Endocrinol. (Oxf) (2007) [Pubmed]
  3. Exclusion of the lim homeodomain gene LHX4 as a candidate gene for pituitary dwarfism in German shepherd dogs. van Oost, B.A., Versteeg, S.A., Imholz, S., Kooistra, H.S. Mol. Cell. Endocrinol. (2002) [Pubmed]
  4. A novel dysfunctional LHX4 mutation with high phenotypical variability in patients with hypopituitarism. Castinetti, F., Saveanu, A., Reynaud, R., Quentien, M.H., Buffin, A., Brauner, R., Kaffel, N., Albarel, F., Guedj, A.M., El Kholy, M., Amin, M., Enjalbert, A., Barlier, A., Brue, T. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  5. Pathophysiology of syndromic combined pituitary hormone deficiency due to a LHX3 defect in light of LHX3 and LHX4 expression during early human development. Sobrier, M.L., Attié-Bitach, T., Netchine, I., Encha-Razavi, F., Vekemans, M., Amselem, S. Gene Expr. Patterns (2004) [Pubmed]
  6. Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4. Machinis, K., Pantel, J., Netchine, I., Léger, J., Camand, O.J., Sobrier, M.L., Dastot-Le Moal, F., Duquesnoy, P., Abitbol, M., Czernichow, P., Amselem, S. Am. J. Hum. Genet. (2001) [Pubmed]
  7. Lhx4 and Prop1 are required for cell survival and expansion of the pituitary primordia. Raetzman, L.T., Ward, R., Camper, S.A. Development (2002) [Pubmed]
  8. Identification of a conserved protein that interacts with specific LIM homeodomain transcription factors. Howard, P.W., Maurer, R.A. J. Biol. Chem. (2000) [Pubmed]
  9. Functional relationship between LHX4 and POU1F1 in light of the LHX4 mutation identified in patients with pituitary defects. Machinis, K., Amselem, S. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  10. cDNA cloning, chromosomal localization and expression pattern analysis of human LIM-homeobox gene LHX4. Liu, Y., Fan, M., Yu, S., Zhou, Y., Wang, J., Yuan, J., Qiang, B. Brain Res. (2002) [Pubmed]
  11. Adrenocorticotrope deficiency with clinical evidence for late onset in combined pituitary hormone deficiency caused by a homozygous 301-302delAG mutation of the PROP1 gene. Lamesch, C., Neumann, S., Pfäffle, R., Kiess, W., Paschke, R. Pituitary (2002) [Pubmed]
 
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