PLAGL1

PLAG1 like zinc finger 1, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 6:143940300-144064599

Links

ENSG00000118495 ∙ NCBI:5325 ∙ OMIM:603044 ∙ HGNC:9046 ∙ Uniprot:Q9UM63 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• transient neonatal diabetes mellitus (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diabetes mellitus, transient neonatal	AD	Endocrine	Individuals present early in life with failure to thrive, hyperglycemia, and dehydration, and prompt recognition and treatment can reduce morbidity	Endocrine	11448939; 20803656
The pathogenesis may involve loss of methylation

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PLAGL1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLAGL1 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				6	6	12
missense			20	3	4	27
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	20	9	10

Variants in PLAGL1

This is a list of pathogenic ClinVar variants found in the PLAGL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-143941451-C-T		PLAGL1-related disorder	Likely benign (Apr 04, 2019)
6-143941495-G-A		Myoepithelial tumor	Uncertain significance (Nov 01, 2022)
6-143941563-A-T		not specified	Uncertain significance (Oct 14, 2023)
6-143941617-T-C		not specified	Uncertain significance (Dec 02, 2022)
6-143941642-G-A		not specified	Uncertain significance (Mar 14, 2023)
6-143941646-G-T			Benign (Aug 20, 2018)
6-143941673-G-T			Likely benign (Feb 01, 2023)
6-143941679-G-A			Likely benign (Apr 12, 2018)
6-143941682-C-T		PLAGL1-related disorder	Benign (May 06, 2019)
6-143941684-G-C		not specified	Uncertain significance (Dec 14, 2023)
6-143941793-T-A			Likely benign (Jan 01, 2023)
6-143941834-T-C		not specified	Uncertain significance (Oct 26, 2022)
6-143941876-C-A		not specified	Uncertain significance (Jun 10, 2024)
6-143941905-T-G		PLAGL1-related disorder	Likely benign (Nov 14, 2017)
6-143941931-C-T			Benign (Aug 22, 2018)
6-143941987-G-A		not specified	Uncertain significance (Mar 20, 2024)
6-143941998-T-C		not specified	Uncertain significance (Jan 04, 2024)
6-143942001-G-A			Benign (Jun 06, 2018)
6-143942003-G-A			Benign (Jun 13, 2018)
6-143942014-G-A		not specified	Likely benign (Dec 15, 2023)
6-143942097-G-C			Likely benign (Aug 21, 2018)
6-143942137-T-C		PLAGL1-related disorder	Benign (Jun 29, 2018)
6-143942155-G-T		not specified	Uncertain significance (Dec 15, 2023)
6-143942159-T-C			Likely benign (May 21, 2018)
6-143942165-C-G		not specified	Uncertain significance (Dec 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLAGL1	protein_coding	protein_coding	ENST00000360537	2	124299

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.976	0.0236	125739	0	6	125745	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.30	198	257	0.772	0.0000133	3021
Missense in Polyphen		47	92.806	0.50643		1070
Synonymous	0.191	109	112	0.977	0.00000609	960
Loss of Function	3.14	0	11.5	0.00	5.29e-7	158

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000334	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a transcriptional activator (PubMed:9722527). Involved in the transcriptional regulation of type 1 receptor for pituitary adenylate cyclase-activating polypeptide. {ECO:0000269|PubMed:18299245, ECO:0000269|PubMed:9722527}.
• Disease: DISEASE: Transient neonatal diabetes mellitus 1 (TNDM1) [MIM:601410]: Neonatal diabetes is a form of diabetes mellitus defined by the onset of mild-to-severe hyperglycemia within the first months of life. In about half of the neonates, diabetes is transient and resolves at a median age of 3 months, whereas the rest have a permanent form of diabetes. {ECO:0000269|PubMed:11935319}. Note=The gene represented in this entry is involved in disease pathogenesis. Imprinted expression of PLAGL1 is relaxed in patients with transient neonatal diabetes (TND) (PubMed:11935319). Aberrant hypomethylation of the TND differentially methylated region within the PLAGL1 promoter as well as other imprinted loci at chromosome 6q24 is caused by ZFP57 mutations (PubMed:18622393). {ECO:0000269|PubMed:11935319, ECO:0000269|PubMed:18622393}.
• Pathway: Aryl Hydrocarbon Receptor;TP53 Regulates Transcription of Cell Cycle Genes;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain;TP53 Regulates Transcription of Cell Cycle Genes;Transcriptional Regulation by TP53 (Consensus)

Recessive Scores

• pRec: 0.195

Intolerance Scores

• loftool: 0.255
• rvis_EVS: -0.16
• rvis_percentile_EVS: 42.06

Haploinsufficiency Scores

• pHI: 0.152
• hipred: N
• hipred_score: 0.441
• ghis: 0.509

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.875

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plagl1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; skeleton phenotype; respiratory system phenotype; embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype

Gene ontology

• Biological process: apoptotic process;DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest;cell cycle arrest;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleoplasm;Golgi apparatus;nuclear body;intracellular membrane-bounded organelle
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;metal ion binding