PLAG1

Highest pathogenic variant AF is 0.0000013683203

Gene type

protein_coding

Transcript type

protein_coding

Transcript

ENST00000316981

Coding exons

2

Length

50421

Individuals with no LoFs

125270

Homozygous LoFs

0

Heterozygous LoFs

1

Defined

125271

p

0.00000399

Function

FUNCTION: Transcription factor whose activation results in up- regulation of target genes, such as IGFII, leading to uncontrolled cell proliferation: when overexpressed in cultured cells, higher proliferation rate and transformation are observed. Other target genes such as CRLF1, CRABP2, CRIP2, PIGF are strongly induced in cells with PLAG1 induction. Proto-oncogene whose ectopic expression can trigger the development of pleomorphic adenomas of the salivary gland and lipoblastomas. Overexpression is associated with up-regulation of IGFII, is frequently observed in hepatoblastoma, common primary liver tumor in childhood. Cooperates with CBFB-MYH11, a fusion gene important for myeloid leukemia. {ECO:0000269|PubMed:11888928, ECO:0000269|PubMed:14695992, ECO:0000269|PubMed:14712223}.;

Disease

DISEASE: Note=A chromosomal aberration involving PLAG1 is found in salivary gland pleiomorphic adenomas, the most common benign epithelial tumors of the salivary gland. Translocation t(3;8)(p21;q12) with constitutively expressed beta-catenin/CTNNB1. Fusion occurs in the 5'-regulatory regions, leading to promoter swapping between the 2 genes and activation of PLAG1 expression in adenomas. The chimeric transcript is formed by fusion of CTNNB1 exon 1 to PLAG1 exon 3. Reciprocal fusion transcript consisting of PLAG1 exon 1 and CTNNB1 exon 2-16 is also revealed in some adenomas (PubMed:9020842, PubMed:10029085). Translocation t(3;8)(p21;q12) with transcription elongation factor SII/TCEA1. The fusion transcript is composed of 5'-non-coding sequences as well as 63 nucleotides of the coding region of TCEA1 fused to the acceptor splice site of PLAG1 exon 3. The fusion transcript encodes a truncated TCEA1-PLAG1 protein of 90 AA as well as an apparently normal PLAG1 protein. Reciprocal fusion transcript PLAG1-TCEA1 is also present in one adenoma (PubMed:10029085, PubMed:16736500). Translocation t(5;8)(p13;q12) with leukemia inhibitory factor receptor LIFR. This fusion occured in the 5'- non-coding sequences of both genes, exchanging regulatory control element while preserving the coding sequences (PubMed:9525740). Translocation t(6;8)(p21.3-22;q13) with Coiled-coil-helix-coiled- coil-helix domain-containing protein 7/CHCHD7. Fusion occurs in the 5' regulatory regions, leading to promoter swapping and up- regulation of PLAG1 expression (PubMed:16736500). Ectopic expression of PLAG1 under the control of promoters of distinct translocation partner genes is a general pathogenetic mechanism for pleiomorphic adenomas with 8q aberrations. These fusion genes are likely to be found in adenomas with normal karyotype as this subgroup of tumors also exhibit PLAG1 activation (PubMed:9020842, PubMed:10029085, PubMed:9525740, PubMed:16736500). {ECO:0000269|PubMed:10029085, ECO:0000269|PubMed:16736500, ECO:0000269|PubMed:9020842, ECO:0000269|PubMed:9525740}.; DISEASE: Note=A chromosomal aberration involving PLAG1 may be a cause of lipoblastomas, which are benign tumors resulting from transformation of adipocytes, usually diagnosed in children. 8q12.1 to 8q24.1 intrachromosomal rearrangement with hyaluronic acid synthase 2/HAS2 results in promoter swapping and activation of PLAG1 expression. The breakpoint of HAS2 gene is in PLAG1 intron 1, whereas its coding sequence starts at exon 2 or exon 3. Translocation t(7;8)(p22;q13) with collagen 1A2/COL1A2. Fusion transcript COL1A2-PLAG1 as well as HAS2-PLAG1 encode a full-length PLAG1 protein. {ECO:0000269|PubMed:10987300, ECO:0000269|PubMed:15642402}.;