PIAS3

protein inhibitor of activated STAT 3, the group of Zinc fingers MIZ-type|MicroRNA protein coding host genes

Basic information

Region (hg38): 1:145848522-145859836

Links

ENSG00000131788 ∙ NCBI:10401 ∙ OMIM:605987 ∙ HGNC:16861 ∙ Uniprot:Q9Y6X2 ∙ 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 PIAS3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIAS3 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				3	1	4
missense			41		1	42
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	42	3	2

Variants in PIAS3

This is a list of pathogenic ClinVar variants found in the PIAS3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-145849463-T-C		not specified	Uncertain significance (Jan 17, 2023)
1-145849471-C-T		not specified	Uncertain significance (Sep 26, 2022)
1-145849534-C-G		not specified	Uncertain significance (Jan 04, 2024)
1-145849537-G-C		not specified	Uncertain significance (Jun 24, 2022)
1-145849546-A-G		not specified	Uncertain significance (Sep 26, 2024)
1-145849550-T-G			Benign (Jun 06, 2017)
1-145849559-G-A		not specified	Uncertain significance (Dec 08, 2023)
1-145849576-G-A		not specified	Uncertain significance (Aug 16, 2021)
1-145849606-G-A		not specified	Uncertain significance (Apr 08, 2022)
1-145849606-G-T		not specified	Uncertain significance (Feb 21, 2024)
1-145849615-A-G		not specified	Uncertain significance (Nov 04, 2023)
1-145849667-G-C		not specified	Uncertain significance (Oct 18, 2021)
1-145849708-T-C		not specified	Uncertain significance (Aug 10, 2023)
1-145850277-G-A			Likely benign (Jul 27, 2018)
1-145850570-G-A		not specified	Uncertain significance (Nov 13, 2023)
1-145850777-C-T		not specified	Uncertain significance (Mar 21, 2024)
1-145850864-A-G		not specified	Uncertain significance (Nov 13, 2023)
1-145850883-C-T		not specified	Uncertain significance (Sep 27, 2024)
1-145850884-G-C			Likely benign (Jan 22, 2018)
1-145850886-C-T		not specified	Uncertain significance (Oct 06, 2023)
1-145850887-C-A		not specified	Uncertain significance (Jan 03, 2025)
1-145850900-T-A		not specified	Uncertain significance (Oct 25, 2022)
1-145851040-G-A		not specified	Uncertain significance (Apr 23, 2024)
1-145851056-A-G		not specified	Uncertain significance (Jun 16, 2023)
1-145851077-T-C		not specified	Uncertain significance (Feb 28, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIAS3	protein_coding	protein_coding	ENST00000393045	14	11314

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.985	0.0150	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.00	298	351	0.849	0.0000204	4017
Missense in Polyphen		103	137.48	0.74919		1593
Synonymous	-1.01	156	141	1.11	0.00000768	1339
Loss of Function	4.43	4	30.4	0.132	0.00000165	353

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000581	0.0000581
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000712	0.0000703
Middle Eastern	0.0000544	0.0000544
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 and the steroid hormone signaling pathway. Involved in regulating STAT3 signaling via inhibiting STAT3 DNA-binding and suppressing cell growth. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation (PubMed:21965678, PubMed:9388184). Sumoylates CCAR2 which promotes its interaction with SIRT1 (PubMed:25406032). Diminishes the sumoylation of ZFHX3 by preventing the colocalization of ZFHX3 with SUMO1 in the nucleus (PubMed:24651376). {ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:24651376, ECO:0000269|PubMed:25406032, ECO:0000269|PubMed:9388184}.
• Pathway: Jak-STAT signaling pathway - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);TGF-Ncore;JAK-STAT-Ncore;Androgen receptor signaling pathway;Prolactin Signaling Pathway;Interleukin-11 Signaling Pathway;Oncostatin M Signaling Pathway;JAK-STAT;EGF-EGFR Signaling Pathway;Interferon type I signaling pathways;DNA Repair;SUMOylation of transcription factors;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;Oncostatin_M;AndrogenReceptor;SUMOylation;EGFR1;Coregulation of Androgen receptor activity;IL11;C-MYB transcription factor network;IL6;Formation of Incision Complex in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Regulation of nuclear SMAD2/3 signaling;IL6-mediated signaling events;Nucleotide Excision Repair (Consensus)

Recessive Scores

• pRec: 0.225

Intolerance Scores

• loftool: 0.259
• rvis_EVS: -0.66
• rvis_percentile_EVS: 15.91

Haploinsufficiency Scores

• pHI: 0.748
• hipred: Y
• hipred_score: 0.840
• ghis: 0.542

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.998

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pias3
• Phenotype: vision/eye phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;response to hormone;positive regulation of gene expression;protein sumoylation;negative regulation of protein sumoylation;positive regulation of protein sumoylation;negative regulation of osteoclast differentiation;positive regulation of membrane potential;TNFSF11-mediated signaling pathway
• Cellular component: nucleoplasm;cytoplasm;nuclear speck;dendrite;synapse
• Molecular function: protein binding;protein C-terminus binding;zinc ion binding;potassium channel regulator activity;SUMO transferase activity;enzyme binding;protein N-terminus binding