PIAS4

protein inhibitor of activated STAT 4, the group of Zinc fingers MIZ-type

Basic information

Region (hg38): 19:4007736-4039386

Links

ENSG00000105229 ∙ NCBI:51588 ∙ OMIM:605989 ∙ HGNC:17002 ∙ Uniprot:Q8N2W9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PIAS4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIAS4 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				10	2	12
missense			26	1		27
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding				1	1	2
Total	0	0	26	12	3

Variants in PIAS4

This is a list of pathogenic ClinVar variants found in the PIAS4 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-4012974-G-C		not specified	Uncertain significance (May 14, 2024)
19-4013051-T-C		PIAS4-related disorder	Likely benign (Apr 25, 2023)
19-4013084-G-C		not specified	Uncertain significance (Feb 28, 2024)
19-4013107-C-T		not specified	Uncertain significance (Jul 20, 2021)
19-4013151-A-G		not specified	Uncertain significance (Nov 12, 2021)
19-4013153-G-A		not specified	Uncertain significance (Jun 25, 2024)
19-4013194-C-T		not specified	Uncertain significance (Apr 08, 2024)
19-4013224-T-C		not specified	Uncertain significance (Aug 01, 2024)
19-4013257-G-C		not specified	Uncertain significance (Apr 07, 2023)
19-4013264-C-T			Benign/Likely benign (Apr 01, 2022)
19-4013265-G-C		not specified	Uncertain significance (Jan 17, 2024)
19-4013278-A-T		PIAS4-related disorder	Likely benign (Oct 25, 2022)
19-4013289-C-T		not specified	Uncertain significance (Dec 15, 2023)
19-4013306-G-A			Likely benign (Apr 17, 2018)
19-4013314-A-C		not specified	Uncertain significance (Nov 30, 2022)
19-4013330-G-A		PIAS4-related disorder	Likely benign (Sep 21, 2022)
19-4028555-G-A			Likely benign (Apr 01, 2022)
19-4028587-A-G		not specified	Uncertain significance (Jul 15, 2021)
19-4028595-G-A		not specified	Uncertain significance (Aug 16, 2021)
19-4028607-A-T			Uncertain significance (Aug 01, 2021)
19-4028736-A-G		not specified	Uncertain significance (Mar 28, 2024)
19-4028785-C-C			Benign (Dec 28, 2018)
19-4028805-C-T		not specified	Uncertain significance (Mar 28, 2024)
19-4028807-G-A		not specified	Uncertain significance (Jul 13, 2021)
19-4028823-C-T		PIAS4-related disorder	Uncertain significance (Sep 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIAS4	protein_coding	protein_coding	ENST00000262971	11	31741

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000139	117428	0	1	117429	0.00000426

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.63	209	347	0.603	0.0000244	3277
Missense in Polyphen		48	142.16	0.33766		1325
Synonymous	-1.81	195	165	1.18	0.0000135	1018
Loss of Function	4.66	0	25.3	0.00	0.00000114	295

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000675	0.0000675
Ashkenazi Jewish	0.00	0.00
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: Functions as an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilizing the interaction between UBE2I and the substrate, and as a SUMO-tethering factor. Plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53/TP53 pathway, the Wnt pathway and the steroid hormone signaling pathway. Involved in gene silencing. Mediates sumoylation of CEBPA, PARK7, HERC2, MYB, TCF4 and RNF168. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation. {ECO:0000269|PubMed:12511558, ECO:0000269|PubMed:12631292, ECO:0000269|PubMed:12727872, ECO:0000269|PubMed:15831457, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:22508508}.
• Pathway: Jak-STAT signaling pathway - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);TGF-Ncore;JAK-STAT-Ncore;Androgen receptor signaling pathway;HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Nonhomologous End-Joining (NHEJ);DNA Double-Strand Break Repair;Metabolism of lipids;SUMOylation of DNA damage response and repair proteins;SUMOylation of transcription factors;Homology Directed Repair;Post-translational protein modification;SUMOylation of DNA replication proteins;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;G2/M DNA damage checkpoint;G2/M Checkpoints;Cell Cycle Checkpoints;Metabolism;Metabolism of steroids;AndrogenReceptor;SUMOylation;Vitamin D (calciferol) metabolism;Coregulation of Androgen receptor activity;IFN-gamma pathway;Cell Cycle;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;Regulation of cytoplasmic and nuclear SMAD2/3 signaling;Processing of DNA double-strand break ends;Regulation of nuclear SMAD2/3 signaling;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.167

Intolerance Scores

• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.27

Haploinsufficiency Scores

• pHI: 0.661
• hipred: Y
• hipred_score: 0.783
• ghis: 0.538

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.962

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pias4
• Phenotype: immune system phenotype; hematopoietic system 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); normal phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;double-strand break repair via nonhomologous end joining;negative regulation of tumor necrosis factor-mediated signaling pathway;Wnt signaling pathway;protein sumoylation;negative regulation of NF-kappaB transcription factor activity;positive regulation of protein sumoylation;vitamin D metabolic process;negative regulation of transcription, DNA-templated;positive regulation of keratinocyte apoptotic process;positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage
• Cellular component: nucleus;nucleoplasm;cytoplasm;nuclear matrix;PML body;transferase complex
• Molecular function: DNA binding;transcription corepressor activity;protein binding;protein C-terminus binding;zinc ion binding;SUMO transferase activity;ubiquitin protein ligase binding;SUMO ligase activity