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Gene Review

PHLDA2  -  pleckstrin homology-like domain, family A,...

Homo sapiens

Synonyms: BRW1C, BWR1C, Beckwith-Wiedemann syndrome chromosomal region 1 candidate gene C protein, HLDA2, IPL, ...
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Disease relevance of PHLDA2


Psychiatry related information on PHLDA2

  • TSSC3 is the first apoptosis-related gene found to be imprinted in placenta, liver and fetal tissues where it is expressed from the maternal allele in normal human development [3].
  • IPL and T/P lesions slowed reaction times (RTs) and increased error rates, but improved one aspect of performance--patients showed less distraction than controls when targets followed novel sounds [5].
  • Statistical analysis of the interpeak latencies of brainstem auditory evoked potentials (BAEP) shows that a delayed IPL I-V is a very sensitive indicator for an early diagnosis of Wernicke's encephalopathy [6].
  • Up to now, the ethology of IPL has not been completely understood [7].
  • Educating women to recognize grief responses after IPL and to manage these responses effectively may prevent adverse outcomes to their physical and mental health [8].

High impact information on PHLDA2

  • DNA hypermethylation was not detected with 5" upstream probes for IPL, IMPT1, KvLQT1 and ZNF195 in WTs or WT-associated kidneys [9].
  • Here we describe mouse and human versions of a novel imprinted gene, IMPT1 , which lies between IPL and p57 KIP2 and which encodes a predicted multi-membrane-spanning protein similar to bacterial and eukaryotic polyspecific metabolite transporter and multi-drug resistance pumps [10].
  • Like several other imprinted genes, mouse and human IPL genes are small and contain small introns [11].
  • Here, we demonstrate that the lack of BWR1C expression is common in WT [12].
  • Sequence analysis suggests that TSSC5 is a membrane protein with 10 transmembrane segments, and it is located between two imprinted genes, p57KIP2 and TSSC3 [13].

Chemical compound and disease context of PHLDA2

  • At the late period of the late regenerating retina with the IPL thickness comparable to that of the control retina, GABA-induced [Ca(2+)](i) rise became undetectable or sometimes a small decrease in [Ca(2+)](i) was observed in regenerated ganglion cells [14].

Biological context of PHLDA2


Anatomical context of PHLDA2

  • PHLDA2 expression in trophoblasts exposed to TGFbeta1, -beta2 or -beta3 was unchanged [1].
  • We initially confirmed that PHLDA2 was expressed in term placental villi, primarily in the trophoblast layer [1].
  • More transparent Spanish words yielded greater activity in superior temporal gyrus (STG; BA 22), a region implicated in phonological processing, and orthographically opaque English words yielded greater activity in visual processing and word recoding regions, such as the occipito-parietal border and inferior parietal lobe (IPL; BA 40) [16].
  • Furthermore, the analysis of psychophysiologic interaction suggests impaired neural interaction in patients with nmHE, especially between the IPL and the parietooccipital cortex (Poc), the intraparietal sulcus, the anterior cingulate cortex (ACC), the right prefrontal cortex (PFC), the medial temporal lobe, and the extrastriate cortex V5 [17].
  • Blue-ON-center signals appeared to be processed mainly in strata 1-2/3, and blue-OFF-center signals in strata 3-5 of the IPL, with contributions of amacrine cells and bipolar cells [18].

Associations of PHLDA2 with chemical compounds

  • The protective effect of c-Jun AS ODN on the NMDA-treated retina was also shown by the RGCL cell count and measurement of the IPL thickness, as well as by quantitative real-time PCR analysis of Thy-1 mRNA 7 days after the injection [19].
  • These labels are found in both the outer and inner plexiform layers (OPL and IPL), suggesting that interplexiform cells (IPCs) contain both Som and glycine in this retina [20].
  • The long-chain PUFA, mainly 20:4n-6 and 22:6n-3 of the n-6 and n-3 series, respectively, were found in high proportion in all phospholipid classes, especially in EPL (46.7 mol%) and in inositol glycerophospholipids (IPL) (39.9 mol%) [21].
  • VPD was partially hydrolyzed to valproic acid (VPA) by the IPL following iv administration to intact rats [22].
  • Nicotine, at comparable concentrations affected only the IPL [23].

Other interactions of PHLDA2

  • In addition, we have identified several novel genes in this region, three of which, termed TSSC1, TSSC2, and TSSC3, are reported here [24].
  • There was strong PHLDA2 staining of the cytoplasm in virtually all cells of the villous cytotrophoblast, while p57KIP2 was localized to the nucleus in a subset of those cells [25].
  • In contrast, other maternal imprinted genes in this region, including p57(KIP2), IMPT1, and IPL exhibited almost normal expression in these samples, although some samples expressed IGF2 biallelically [26].

Analytical, diagnostic and therapeutic context of PHLDA2

  • Using quantitative PCR we found that the expression of PHLDA2 gradually declined during differentiation of primary term human trophoblasts [1].
  • Differential diagnosis between complete and partial mole using a TSSC3 antibody: correlation with DNA polymorphic marker analysis [27].
  • In all 20 CHM cases for which the diagnosis had been confirmed by DNA polymorphic markers, the expression of TSSC3 was completely lost on Western blots [27].
  • IPL protein was absent in both of two cases of androgenetic complete hydatidiform mole examined by immunostaining, and IPL mRNA was absent in an additional three cases of this neoplasm examined by northern blotting [28].
  • In this report, we present a novel method for the facile production of a peptide affinity column by employing intein-mediated protein ligation (IPL) in conjunction with chitin affinity chromatography [29].


  1. Hypoxia Regulates the Expression of PHLDA2 in Primary Term Human Trophoblasts. Kim, H.S., Roh, C.R., Chen, B., Tycko, B., Nelson, D.M., Sadovsky, Y. Placenta (2007) [Pubmed]
  2. Unbalanced placental expression of imprinted genes in human intrauterine growth restriction. McMinn, J., Wei, M., Schupf, N., Cusmai, J., Johnson, E.B., Smith, A.C., Weksberg, R., Thaker, H.M., Tycko, B. Placenta (2006) [Pubmed]
  3. Retention of imprinting of the human apoptosis-related gene TSSC3 in human brain tumors. Müller, S., van den Boom, D., Zirkel, D., Köster, H., Berthold, F., Schwab, M., Westphal, M., Zumkeller, W. Hum. Mol. Genet. (2000) [Pubmed]
  4. Elevated placental expression of the imprinted PHLDA2 gene is associated with low birth weight. Apostolidou, S., Abu-Amero, S., O'donoghue, K., Frost, J., Olafsdottir, O., Chavele, K.M., Whittaker, J.C., Loughna, P., Stanier, P., Moore, G.E. J. Mol. Med. (2007) [Pubmed]
  5. Anatomical substrates of auditory selective attention: behavioral and electrophysiological effects of posterior association cortex lesions. Woods, D.L., Knight, R.T., Scabini, D. Brain research. Cognitive brain research. (1993) [Pubmed]
  6. The value of brainstem auditory evoked potentials in early diagnosis of Wernicke's encephalopathy. Haas, W., Nickel, B. Alcohol Alcohol. (1991) [Pubmed]
  7. Inflammatory pseudotumor of the liver: case report and review of the literature. Mangiante, G.L., Colombari, R., Portuese, A., Bortolasi, L., Marinello, P., Colucci, G., Montresor, E., Serio, G.E. Il Giornale di chirurgia. (1997) [Pubmed]
  8. Coping with grief after involuntary pregnancy loss: perspectives of African American women. Van, P., Meleis, A.I. Journal of obstetric, gynecologic, and neonatal nursing : JOGNN / NAACOG. (2003) [Pubmed]
  9. Multipoint analysis of human chromosome 11p15/mouse distal chromosome 7: inclusion of H19/IGF2 in the minimal WT2 region, gene specificity of H19 silencing in Wilms' tumorigenesis and methylation hyper-dependence of H19 imprinting. Dao, D., Walsh, C.P., Yuan, L., Gorelov, D., Feng, L., Hensle, T., Nisen, P., Yamashiro, D.J., Bestor, T.H., Tycko, B. Hum. Mol. Genet. (1999) [Pubmed]
  10. IMPT1, an imprinted gene similar to polyspecific transporter and multi-drug resistance genes. Dao, D., Frank, D., Qian, N., O'Keefe, D., Vosatka, R.J., Walsh, C.P., Tycko, B. Hum. Mol. Genet. (1998) [Pubmed]
  11. The IPL gene on chromosome 11p15.5 is imprinted in humans and mice and is similar to TDAG51, implicated in Fas expression and apoptosis. Qian, N., Frank, D., O'Keefe, D., Dao, D., Zhao, L., Yuan, L., Wang, Q., Keating, M., Walsh, C., Tycko, B. Hum. Mol. Genet. (1997) [Pubmed]
  12. Abnormal RNA expression of 11p15 imprinted genes and kidney developmental genes in Wilms' tumor. Schwienbacher, C., Angioni, A., Scelfo, R., Veronese, A., Calin, G.A., Massazza, G., Hatada, I., Barbanti-Brodano, G., Negrini, M. Cancer Res. (2000) [Pubmed]
  13. Somatic mutation of TSSC5, a novel imprinted gene from human chromosome 11p15.5. Lee, M.P., Reeves, C., Schmitt, A., Su, K., Connors, T.D., Hu, R.J., Brandenburg, S., Lee, M.J., Miller, G., Feinberg, A.P. Cancer Res. (1998) [Pubmed]
  14. GABAA-receptor-mediated increase in intracellular Ca2+ concentration in the regenerating retina of adult newt. Ohmasa, M., Saito, T. Neurosci. Res. (2004) [Pubmed]
  15. Upregulation of PHLDA2 in Dicer knockdown HEK293 cells. Tang, K.F., Wang, Y., Wang, P., Chen, M., Chen, Y., Hu, H.D., Hu, P., Wang, B., Yang, W., Ren, H. Biochim. Biophys. Acta (2007) [Pubmed]
  16. Impact of language proficiency and orthographic transparency on bilingual word reading: an fMRI investigation. Meschyan, G., Hernandez, A.E. Neuroimage (2006) [Pubmed]
  17. Neural mechanism underlying impaired visual judgement in the dysmetabolic brain: an fMRI study. Zafiris, O., Kircheis, G., Rood, H.A., Boers, F., Häussinger, D., Zilles, K. Neuroimage (2004) [Pubmed]
  18. The organization of the turtle inner retina. II. Analysis of color-coded and directionally selective cells. Ammermüller, J., Muller, J.F., Kolb, H. J. Comp. Neurol. (1995) [Pubmed]
  19. Pro-apoptotic role of c-Jun in NMDA-induced neurotoxicity in the rat retina. Munemasa, Y., Ohtani-Kaneko, R., Kitaoka, Y., Kumai, T., Kitaoka, Y., Hayashi, Y., Watanabe, M., Takeda, H., Hirata, K., Ueno, S. J. Neurosci. Res. (2006) [Pubmed]
  20. Glycine high-affinity uptake labels a subpopulation of somatostatin-like immunoreactive cells in the Rana pipiens retina. Smiley, J.F., Basinger, S.F. Brain Res. (1989) [Pubmed]
  21. Phospholipid molecular species from human placenta lipids. Bayon, Y., Croset, M., Chirouze, V., Tayot, J.L., Lagarde, M. Lipids (1993) [Pubmed]
  22. The disposition of valpromide in rats and the isolated perfused rat liver. Billig, H., Ziv, E., Bar-On, H., Bialer, M. Drug Metab. Dispos. (1990) [Pubmed]
  23. Two types of receptors for alpha-bungarotoxin in the synaptic layers of the pigeon retina. Yazulla, S., Schmidt, J. Brain Res. (1977) [Pubmed]
  24. A 2.5-Mb transcript map of a tumor-suppressing subchromosomal transferable fragment from 11p15.5, and isolation and sequence analysis of three novel genes. Hu, R.J., Lee, M.P., Connors, T.D., Johnson, L.A., Burn, T.C., Su, K., Landes, G.M., Feinberg, A.P. Genomics (1997) [Pubmed]
  25. Immunohistochemistry for the imprinted gene product IPL/PHLDA2 for facilitating the differential diagnosis of complete hydatidiform mole. Thaker, H.M., Berlin, A., Tycko, B., Goldstein, D.P., Berkowitz, R.S., Castrillon, D.H., Genest, D.R. The Journal of reproductive medicine. (2004) [Pubmed]
  26. A novel imprinted gene, KCNQ1DN, within the WT2 critical region of human chromosome 11p15.5 and its reduced expression in Wilms' tumors. Xin, Z., Soejima, H., Higashimoto, K., Yatsuki, H., Zhu, X., Satoh, Y., Masaki, Z., Kaneko, Y., Jinno, Y., Fukuzawa, R., Hata, J., Mukai, T. J. Biochem. (2000) [Pubmed]
  27. Differential diagnosis between complete and partial mole using a TSSC3 antibody: correlation with DNA polymorphic marker analysis. Kato, H., Wake, N. The Journal of reproductive medicine (2006) [Pubmed]
  28. The product of the imprinted gene IPL marks human villous cytotrophoblast and is lost in complete hydatidiform mole. Saxena, A., Frank, D., Panichkul, P., Van den Veyver, I.B., Tycko, B., Thaker, H. Placenta (2003) [Pubmed]
  29. Generation of an affinity column for antibody purification by intein-mediated protein ligation. Sun, L., Ghosh, I., Xu, M.Q. J. Immunol. Methods (2003) [Pubmed]
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