PHLDA2

General Information

Full gene name:pleckstrin homology-like domain, family A, member 2 Entrez Gene ID:7262 Location:11p15.4 Synonyms:BWR1C, HLDA2, BRW1C, IPL, TSSC3 Type:protein-coding

User SNPs

SNPs given by the user that are near or inside this gene:

SNP	Distance (bp)	Direction
rs2237892	109752	downstream

NCBI Summary

This gene is located in a cluster of imprinted genes on chromosome 11p15.5, which is considered to be an important tumor suppressor gene region. Alterations in this region may be associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene has been shown to be imprinted, with preferential expression from the maternal allele in placenta and liver. [provided by RefSeq, Oct 2010]

OMIM

OMIM ID:`OMIM ID 602131 `_

NCBI Phenotypes

• Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels.
• NHGRI GWA Catalog

Gene Ontology

• organ morphogenesis
• membrane
• phospholipid binding
• apoptotic process
• cytoplasm

KEGG Pathways

No pathways found linked to this gene.

GeneRIFs

• PHLDA2 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. [PMID 21555518]
• Exposure of trophoblasts to hypoxia in vitro markedly reduced the expression of PHLDA2. [PMID 16584773]
• The results suggest that placental PHLDA2 may provide a biomarker for suboptimal skeletal growth in pregnancies uncomplicated by overt fetal growth restriction. [PMID 22100507]
• Up-regulation of TSSC3 occurred in Dicer knockdown cells. [PMID 17303335]
• Observational study and genome-wide association study of gene-disease association. (HuGE Navigator) [PMID 20201924]
• A luciferase reporter assay was used to identify in the PHLDA2 promoter a 15 bp repeat sequence variant that significantly reduces PHLDA2-promoter efficiency. Maternal inheritance of the variant resulted in a significant increase in birth weight. [PMID 22444668]
• PHLDA2 gene is imprinted, with preferential expression from the maternal allele in placenta and liver. [PMID 9328465]
• TSSC3 has a potent tumor suppressor role in osteosarcoma, probably by inhibition of growth and induction of apoptosis via the mitochondrial apoptosis pathway. [PMID 22021909]
• association with low birth weight [PMID 17180344]
• Transcripts of TSSC3 could not be detected in human oocytes and preimplantation embryos. [PMID 15952111]
• Expression levels of PHLDA2 gene were upregulated in the first trimester pregnancy [PMID 20484977]
• Affinity Capture-MS [PMID 21906983]

PubMed Articles

Recent articles:

• Ishida M et al. “Maternal inheritance of a promoter variant in the imprinted PHLDA2 gene significantly increases birth weight.” Am J Hum Genet. 2012 Apr 6;90(4):715-9. PMID 22444668
• Lewis RM et al. “Relationship between placental expression of the imprinted PHLDA2 gene, intrauterine skeletal growth and childhood bone mass.” Bone. 2012 Jan;50(1):337-42. PMID 22100507
• Dai H et al. “TSSC3 overexpression associates with growth inhibition, apoptosis induction and enhances chemotherapeutic effects in human osteosarcoma.” Carcinogenesis. 2012 Jan;33(1):30-40. PMID 22021909
• Kim W et al. “Systematic and quantitative assessment of the ubiquitin-modified proteome.” Mol Cell. 2011 Oct 21;44(2):325-40. PMID 21906983
• Warnatz HJ et al. “The BTB and CNC homology 1 (BACH1) target genes are involved in the oxidative stress response and in control of the cell cycle.” J Biol Chem. 2011 Jul 1;286(26):23521-32. PMID 21555518
• O’Seaghdha CM et al. “Common variants in the calcium-sensing receptor gene are associated with total serum calcium levels.” Hum Mol Genet. 2010 Nov 1;19(21):4296-303. PMID 20705733
• Dória S et al. “Gene expression pattern of IGF2, PHLDA2, PEG10 and CDKN1C imprinted genes in spontaneous miscarriages or fetal deaths.” Epigenetics. 2010 Jul 1;5(5):444-50. PMID 20484977
• Edenberg HJ et al. “Genome-wide association study of alcohol dependence implicates a region on chromosome 11.” Alcohol Clin Exp Res. 2010 May;34(5):840-52. PMID 20201924
• Tang KF et al. “Upregulation of PHLDA2 in Dicer knockdown HEK293 cells.” Biochim Biophys Acta. 2007 May;1770(5):820-5. PMID 17303335
• Bertheau P et al. “Exquisite sensitivity of TP53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen.” PLoS Med. 2007 Mar;4(3):e90. PMID 17388661

Top Pubmed articles linked to gene PHLDA2 matching any search term:

• Turan N et al. “DNA methylation differences at growth related genes correlate with birth weight: a molecular signature linked to developmental origins of adult disease?.” BMC Med Genomics. 2012 Apr 12;5:10. PMID 22498030
• Kumar N et al. “Ontogeny of growth-regulating genes in the placenta.” Placenta. 2012 Feb;33(2):94-9. PMID 22154689
• Shukla PK et al. “Candidate placental biomarkers for intrauterine alcohol exposure.” Alcohol Clin Exp Res. 2011 Mar;35(3):559-65. PMID 21143252
• Dória S et al. “Gene expression pattern of IGF2, PHLDA2, PEG10 and CDKN1C imprinted genes in spontaneous miscarriages or fetal deaths.” Epigenetics. 2010 Jul 1;5(5):444-50. PMID 20484977
• Apostolidou S et al. “Elevated placental expression of the imprinted PHLDA2 gene is associated with low birth weight.” J Mol Med (Berl). 2007 Apr;85(4):379-87. PMID 17180344
• Duselis AR et al. “Assessment and disease comparisons of hybrid developmental defects.” Hum Mol Genet. 2007 Apr 1;16(7):808-19. PMID 17339267
• Kim HS et al. “Hypoxia regulates the expression of PHLDA2 in primary term human trophoblasts.” Placenta. 2007 Feb-Mar;28(2-3):77-84. PMID 16584773
• Frank D et al. “Placental overgrowth in mice lacking the imprinted gene Ipl.” Proc Natl Acad Sci U S A. 2002 May 28;99(11):7490-5. PMID 12032310
• Feinberg AP et al. “Imprinting of a genomic domain of 11p15 and loss of imprinting in cancer: an introduction.” Cancer Res. 1999 Apr 1;59(7 Suppl):1743s-1746s. PMID 10197590