PLAG1

PLAG1 zinc finger, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 8:56160909-56211324

Links

ENSG00000181690 ∙ NCBI:5324 ∙ OMIM:603026 ∙ HGNC:9045 ∙ Uniprot:Q6DJT9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• silver-russell syndrome 4 (Moderate), mode of inheritance: AD
• silver-russell syndrome 4 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Silver-Russell syndrome 4	AD	Endocrine	Among other findings, response to growth hormone therapy has been described, and awareness may allow early diagnosis and management of this issue	Craniofacial; Endocrine; Musculoskeletal	28796236

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLAG1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLAG1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			19	3	1	23
nonsense		1	1			2
start loss						0
frameshift		3	3			6
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	4	23	3	1

Variants in PLAG1

This is a list of pathogenic ClinVar variants found in the PLAG1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-56166285-G-C			Uncertain significance (Dec 01, 2022)
8-56166289-A-C			Uncertain significance (Mar 18, 2022)
8-56166338-T-C		Inborn genetic diseases	Uncertain significance (Jan 09, 2024)
8-56166347-C-A		Inborn genetic diseases	Uncertain significance (Jun 10, 2024)
8-56166373-G-C		not specified	Uncertain significance (Jan 18, 2023)
8-56166374-G-T			Benign (Mar 17, 2022)
8-56166378-G-GA			Uncertain significance (Oct 02, 2019)
8-56166382-TG-T		Silver-Russell syndrome 1 • Silver-russell syndrome 4	Pathogenic (Jun 15, 2020)
8-56166389-C-G		PLAG1-related disorder	Likely benign (Dec 21, 2022)
8-56166400-G-A		Inborn genetic diseases • PLAG1-related disorder	Uncertain significance (Dec 28, 2022)
8-56166485-A-C		Inborn genetic diseases	Uncertain significance (Nov 21, 2022)
8-56166518-G-A		Inborn genetic diseases	Uncertain significance (Mar 04, 2024)
8-56166533-T-C		Inborn genetic diseases	Uncertain significance (Dec 03, 2021)
8-56166548-GGGAGAGGT-G		Intellectual disability	Likely pathogenic (-)
8-56166591-A-C		Inborn genetic diseases	Likely benign (Dec 06, 2022)
8-56166616-G-A		Inborn genetic diseases	Uncertain significance (Oct 26, 2024)
8-56166653-C-G		Inborn genetic diseases	Uncertain significance (Apr 22, 2024)
8-56166670-T-TA		PLAG1-related disorder	Likely pathogenic (Sep 26, 2022)
8-56166685-C-T		Inborn genetic diseases	Uncertain significance (Dec 28, 2022)
8-56166721-G-A			Uncertain significance (Oct 17, 2023)
8-56166784-A-G		Inborn genetic diseases	Uncertain significance (Sep 08, 2024)
8-56166791-T-A		Inborn genetic diseases	Uncertain significance (Oct 30, 2024)
8-56166844-G-A		Inborn genetic diseases	Uncertain significance (Jul 26, 2022)
8-56166847-C-T			Uncertain significance (Jun 16, 2024)
8-56166852-C-A		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLAG1	protein_coding	protein_coding	ENST00000316981	2	50421

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.995	0.00468	125270	0	1	125271	0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.25	164	267	0.613	0.0000144	3289
Missense in Polyphen		71	139.66	0.50837		1651
Synonymous	-0.776	114	104	1.10	0.00000581	980
Loss of Function	3.69	0	15.9	0.00	9.13e-7	211

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000996	0.0000996
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: miR-targeted genes in lymphocytes - TarBase (Consensus)

Recessive Scores

• pRec: 0.198

Intolerance Scores

• loftool: 0.102
• rvis_EVS: -0.23
• rvis_percentile_EVS: 37.11

Haploinsufficiency Scores

• pHI: 0.850
• hipred: Y
• hipred_score: 0.673
• ghis: 0.589

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Plag1
• Phenotype: reproductive system phenotype; embryo phenotype; vision/eye phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: transcription, DNA-templated;regulation of transcription, DNA-templated;negative regulation of gene expression;gland morphogenesis;multicellular organism growth;positive regulation of transcription by RNA polymerase II;positive regulation of glial cell proliferation;prostate gland growth
• Cellular component: nucleus;nuclear speck
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;metal ion binding