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Gene Review

UBL4A  -  ubiquitin-like 4A

Homo sapiens

Synonyms: DX254E, DXS254E, G6PD, GDX, GET5, ...
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Disease relevance of UBL4A

  • Y-negative XX males belong to the same clinical spectrum as XX true hermaphrodites, and gonadal dysgenesis in some XY females may be due to sporadic or familial mutations of GDX [1].

High impact information on UBL4A


Biological context of UBL4A

  • The findings in most cases are consistent with the hypothesis of homologous gonad-determining genes, GDX and GDY, carried by the X and Y chromosomes respectively [1].
  • The depletion of endogenous androgens by GDX significantly augmented lesion severity, consistent with the hypothesis that androgens are involved in maintaining cell viability [3].
  • It is postulated that in sporadic or familial XX true hermaphrodites one of the GDX loci escapes X-inactivation because of mutation or chromosomal rearrangement, resulting in mosaicism for testis and ovary-determining cell lines in somatic cells [1].
  • We find that the five human X-linked genes (G6PD, GDX, F9, AR and MCF2) map to the echidna X1 chromosome in locations equivalent to those on the platypus X [4].
  • The data indicate that GDX enhances gene expression of both TH and NET [5].

Anatomical context of UBL4A

  • INTERVENTION: The RNFL thickness was assessed with a scanning laser polarimeter (Nerve Fiber Analyzer GDX, Laser Diagnostic Technologies Inc., San Diego, CA) [6].
  • To investigate how gonadal steroids influence noradrenergic neuronal activities in the locus coeruleus (LC), mRNA levels of tyrosine hydroxylase (TH) and NE transporter (NET), two key factors regulating NE synthesis and uptake, were compared 3 weeks after gonadectomy (GDX) [5].
  • Second, we hypothesized that, if androgens' effects are due in part to actions of 3alpha-diol in the hippocampus, then systemic or intrahippocampal administration of 3alpha-diol should significantly enhance cognitive performance of GDX male rats [7].

Associations of UBL4A with chemical compounds

  • Since gonadectomy (GDX) attenuates LTF in male rats, we tested the hypotheses that: (1) testosterone replenishment restores LTF in gonadectomized male rats, and (2) that the conversion of testosterone to oestradiol (under the influence of aromatase) is required for these effects [8].
  • Importantly, DHT hormone replacement in GDX rats significantly attenuated kainate-induced neuron loss in CA2/3, suggesting direct androgen neuroprotection [3].
  • Adult male rats were maintained in the following conditions: i) gonadectomized (GDX) to deplete endogenous androgens, ii) GDX+replacement with dihydrotestosterone (DHT) the active and non-aromatizable testosterone metabolite, iii) sham-GDX [3].
  • Three weeks after gonadectomy (GDX) or sham-surgery (INT), animals were randomly divided into groups to be left in the home cage as controls (HC) or to be exposed to Sham (S) or Formalin (F) stimuli (s.c. formalin injection, 50 microl, 5%, in the dorsal hind paw) in the subsequent 2 weeks (Trial 1; Trial 2) [9].
  • In those studies, AR mRNA levels were up-regulated after 1 day of treatment with exogenous TP in FMN of gonadectomized (GDX) males and after 7 days in FMN of intact females, with no effects in GDX females [10].

Analytical, diagnostic and therapeutic context of UBL4A

  • In men, orchiectomy (GDX) produces an atherogenic lipid profile, whereas combined androgen blockade (CAB) induces a favorable lipid pattern [2].
  • Semi-quantitative RT-PCR revealed a significant elevation of FSHbeta, but not LHbeta, in mature male R. pipiens 21 days after gonadectomy (GDX) [11].


  1. Accidental X-Y recombination and the aetiology of XX males and true hermaphrodites. Ferguson-Smith, M.A., Affara, N.A. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (1988) [Pubmed]
  2. Plasma lipoprotein profile in the male cynomolgus monkey under normal, hypogonadal, and combined androgen blockade conditions. Leblanc, M., Bélanger, M.C., Julien, P., Tchernof, A., Labrie, C., Bélanger, A., Labrie, F. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  3. Androgens modulate neuronal vulnerability to kainate lesion. Ramsden, M., Shin, T.M., Pike, C.J. Neuroscience (2003) [Pubmed]
  4. Gene mapping studies confirm the homology between the platypus X and echidna X1 chromosomes and identify a conserved ancestral monotreme X chromosome. Watson, J.M., Riggs, A., Graves, J.A. Chromosoma (1992) [Pubmed]
  5. Gonadectomy alters tyrosine hydroxylase and norepinephrine transporter mRNA levels in the locus coeruleus in rabbits. Yang, S.P., Pau, K.Y., Spies, H.G. J. Neuroendocrinol. (1997) [Pubmed]
  6. Retinal nerve fiber layer measurement by nerve fiber analyzer in normal subjects and patients with glaucoma. Lee, V.W., Mok, K.H. Ophthalmology (1999) [Pubmed]
  7. Androgens' effects to enhance learning may be mediated in part through actions at estrogen receptor-beta in the hippocampus. Edinger, K.L., Frye, C.A. Neurobiology of learning and memory (2007) [Pubmed]
  8. Conversion from testosterone to oestradiol is required to modulate respiratory long-term facilitation in male rats. Zabka, A.G., Mitchell, G.S., Behan, M. J. Physiol. (Lond.) (2006) [Pubmed]
  9. Repeated nociceptive stimulation induces different behavioral and neuronal responses in intact and gonadectomized female rats. Ceccarelli, I., Fiorenzani, P., Massafra, C., Aloisi, A.M. Brain Res. (2006) [Pubmed]
  10. Regulation of androgen receptor mRNA expression in hamster facial motoneurons: differential effects of non-aromatizable and aromatizable androgens. Drengler, S.M., Handa, R.J., Jones, K.J. Brain Res. Mol. Brain Res. (1996) [Pubmed]
  11. Characterization and steroidal regulation of gonadotropin beta subunits in the male leopard frog, Rana pipiens. Zhang, L., Kessler, A.E., Tsai, P.S. Gen. Comp. Endocrinol. (2007) [Pubmed]
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