PLAGL1 (Pleomorphic adenoma gene-like 1)

2007-08-01   Abbas Abdollahi 

Sbarro Institute for Cancer Research, Molecular Medicine, College of Science, Technology, BioLife Sciences Building, Suite 446, Temple University, 1900 North 12th Street, Philadelphia, PA 19122, USA

Identity

HGNC
PLAGL1
LOCATION
6q24.2
LOCUSID
5325
ALIAS
LOT1,ZAC,ZAC1
FUSION GENES
Show Gene Fusions

DNA/RNA

Atlas Image
Schematic view of the PLAGL1 gene. A. The six exons, shown in red, are 326; 72; 1443; 75; 475; 2380 bp, respectively. The introns are approximately 39; 2.6; 4.2; 12.5; 5.5 kbp in size, respectively. B. The figure shows three splice variants of PLAGL1; the exons are shown as a box.

Description

The genome is about 64 kbp with six exons and five introns. The major mRNA transcript is about 4.7 kb in size.

Transcription

At least three splicing variants (See Figure, above)

Proteins

Description

The PLAGL1 protein is a seven C2H2-type zinc finger protein. The seven zinc finger domain is located at the amino terminal region, from the amino acid residue 1 to 210. Additional features of note are proline and glutamine rich regions at the carboxyl terminal portion (residues 220 to 444). There are two nuclear localization signals at the amino terminal region.

Expression

Ovary, breast, brain, liver, spleen, thymus, prostate, uterus, testis, intestine, colon, leukocytes.

Localisation

Nuclear

Function

The PLAGL1 protein is a candidate tumor suppressor gene and has been shown to have transactivation and DNA-binding activity and to exhibit antiproliferative activities.

Homology

Homologous to the mouse and Rat plagl1 and to the human PLAG1 and PLAGL2 proteins.

Mutations

Note

Mutation has not been found in the PLAGL1 coding region.

Implicated in

Entity name
Carcinogenicity
Note
Alteration of the gene expression was found to be a potential genetic event silencing the PLAGL1 gene in cancers such as breast primary tumors, ovarian primary tumors and tumor-derived cell lines, basal cell carcinoma, head and neck squamous cell carcinoma (HNSCC), and extraskeletal myxoid chondrosarcoma (EMC). Several mechanisms have been shown to regulate the PLAGL1 gene expression, including growth factor receptor activation, epigenetic factors, maternal imprinting, and loss of heterozygosity (LOH). Allelic deletion of 6q24-q25, the PLAGL1 locus, in the tumor tissues has been shown in the cancers of ovarian, breast, HNSCC, and pheochromocytomas (PCCs).
Disease
Cancer
Entity name
Transient Neonatal Diabetes (TNDM)
Note
Initial reports suggested that transient neonatal diabetes mellitus (TNDM), a rare condition characterized in the patients by intrauterine growth retardation, dehydration, failure to thrive, and hyperglycemia due to a lack of normal insulin secretion, is associated with paternal uniparental disomy (UPD) of chromosome 6 (UPD 6). Later studies showed the involvement of an imprinted gene in this disease within the chromosomal region 6q24.1-q24.3 between markers D6S1699 and D6S1010. Analysis of the CpG islands in the TNDM critical region, using DNA from TNDM patients with paternal UPD 6 and normal controls, suggested PLAGL1/LOT1/ZAC1 as a candidate imprinted gene for this disease.
Disease
Diabetes mellitus

Bibliography

Pubmed IDLast YearTitleAuthors

Other Information

Locus ID:

NCBI: 5325
MIM: 603044
HGNC: 9046
Ensembl: ENSG00000118495

Variants:

dbSNP: 5325
ClinVar: 5325
TCGA: ENSG00000118495
COSMIC: PLAGL1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000118495ENST00000354765Q9UM63
ENSG00000118495ENST00000360537Q9UM63
ENSG00000118495ENST00000367571Q9UM63
ENSG00000118495ENST00000367572Q9UM63
ENSG00000118495ENST00000392307Q68DN7
ENSG00000118495ENST00000416623Q9UM63
ENSG00000118495ENST00000417959Q9UM63
ENSG00000118495ENST00000437412Q9UM63
ENSG00000118495ENST00000444202Q9UM63
ENSG00000118495ENST00000625622Q9UM63
ENSG00000118495ENST00000626294A0A0D9SGF7
ENSG00000118495ENST00000626373A1YLA2
ENSG00000118495ENST00000626462A0A0D9SFM8
ENSG00000118495ENST00000627449A0A0D9SEQ4
ENSG00000118495ENST00000628651A0A0D9SFI7
ENSG00000118495ENST00000629195A1YLA1
ENSG00000118495ENST00000647880Q9UM63
ENSG00000118495ENST00000647988A0A3B3IRN7
ENSG00000118495ENST00000649211Q9UM63
ENSG00000118495ENST00000649307Q9UM63
ENSG00000118495ENST00000650125Q9UM63

Expression (GTEx)

0
10
20
30
40
50
60
70
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
TP53 Regulates Transcription of Cell Cycle GenesREACTOMER-HSA-6791312
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertainREACTOMER-HSA-6804115

References

Pubmed IDYearTitleCitations
106555562000The cell cycle control gene ZAC/PLAGL1 is imprinted--a strong candidate gene for transient neonatal diabetes.55
152868002004Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM.42
158887262005ZAC, LIT1 (KCNQ1OT1) and p57KIP2 (CDKN1C) are in an imprinted gene network that may play a role in Beckwith-Wiedemann syndrome.35
125294032003Transcriptional activities of the zinc finger protein Zac are differentially controlled by DNA binding.27
173414872007Tissue-specific imprinting of the ZAC/PLAGL1 tumour suppressor gene results from variable utilization of monoallelic and biallelic promoters.26
204875062010A whole genome association study of mother-to-child transmission of HIV in Malawi.26
124736472003LOT1 (PLAGL1/ZAC1), the candidate tumor suppressor gene at chromosome 6q24-25, is epigenetically regulated in cancer.25
243167532014Degree of methylation of ZAC1 (PLAGL1) is associated with prenatal and post-natal growth in healthy infants of the EDEN mother child cohort.24
155926632004Neonatal diabetes, with hypoplastic pancreas, intestinal atresia and gall bladder hypoplasia: search for the aetiology of a new autosomal recessive syndrome.23
119353192002Relaxation of imprinted expression of ZAC and HYMAI in a patient with transient neonatal diabetes mellitus.22

Citation

Abbas Abdollahi

PLAGL1 (Pleomorphic adenoma gene-like 1)

Atlas Genet Cytogenet Oncol Haematol. 2007-08-01

Online version: http://atlasgeneticsoncology.org/gene/41737/cancer-prone-explorer/