PIAS2

protein inhibitor of activated STAT 2, the group of Zinc fingers MIZ-type

Basic information

Region (hg38): 18:46803218-46920160

Links

ENSG00000078043 ∙ NCBI:9063 ∙ OMIM:603567 ∙ HGNC:17311 ∙ Uniprot:O75928 ∙ 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 PIAS2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIAS2 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					1	1
missense			31		1	32
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	31	0	2

Variants in PIAS2

This is a list of pathogenic ClinVar variants found in the PIAS2 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-46812438-C-T		not specified	Uncertain significance (Jun 28, 2022)
18-46812474-T-C		not specified	Uncertain significance (Dec 21, 2023)
18-46812480-T-C			Benign (Oct 23, 2018)
18-46812493-A-T		not specified	Uncertain significance (Jan 22, 2024)
18-46812532-A-T		not specified	Uncertain significance (Apr 09, 2024)
18-46812548-G-A		not specified	Uncertain significance (Nov 27, 2024)
18-46812564-T-C		not specified	Uncertain significance (Dec 10, 2024)
18-46812590-T-C		not specified	Uncertain significance (Dec 28, 2023)
18-46820951-T-C		not specified	Uncertain significance (Apr 07, 2023)
18-46820986-T-C		not specified	Uncertain significance (Jan 29, 2025)
18-46821008-T-C		not specified	Uncertain significance (Apr 26, 2023)
18-46821008-T-G		not specified	Uncertain significance (Jan 23, 2024)
18-46821017-G-T		not specified	Uncertain significance (Mar 02, 2023)
18-46821063-C-T		not specified	Uncertain significance (Jun 30, 2022)
18-46828046-A-G		not specified	Uncertain significance (Jul 27, 2022)
18-46828122-C-T		not specified	Uncertain significance (Sep 22, 2022)
18-46829757-C-G		not specified	Uncertain significance (Nov 10, 2024)
18-46836358-C-T		not specified	Uncertain significance (Dec 16, 2022)
18-46844764-T-C		not specified	Uncertain significance (Aug 12, 2021)
18-46846783-T-C		not specified	Uncertain significance (Mar 28, 2024)
18-46855381-T-C			Benign (Mar 29, 2018)
18-46864208-A-C		not specified	Uncertain significance (May 30, 2023)
18-46890619-A-G		not specified	Uncertain significance (Jul 25, 2023)
18-46890628-G-T		not specified	Uncertain significance (Sep 22, 2022)
18-46890630-T-C		not specified	Uncertain significance (Dec 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIAS2	protein_coding	protein_coding	ENST00000585916	14	111771

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00282	125740	0	6	125746	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.06	226	331	0.682	0.0000168	4045
Missense in Polyphen		16	38.264	0.41815		488
Synonymous	0.947	107	120	0.890	0.00000637	1212
Loss of Function	4.61	3	30.5	0.0984	0.00000164	392

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000152	0.000152
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000884	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000655	0.0000653
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 coregulator in various cellular pathways, including the STAT pathway, the p53 pathway and the steroid hormone signaling pathway. The effects of this transcriptional coregulation, transactivation or silencing may vary depending upon the biological context and the PIAS2 isoform studied. However, it seems to be mostly involved in gene silencing. Binds to sumoylated ELK1 and enhances its transcriptional activity by preventing recruitment of HDAC2 by ELK1, thus reversing SUMO-mediated repression of ELK1 transactivation activity. Isoform PIAS2-beta, but not isoform PIAS2-alpha, promotes MDM2 sumoylation. Isoform PIAS2-alpha promotes PARK7 sumoylation. Isoform PIAS2-beta promotes NCOA2 sumoylation more efficiently than isoform PIAS2- alpha. Isoform PIAS2-alpha sumoylates PML at'Lys-65' and 'Lys- 160'. {ECO:0000269|PubMed:15920481, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:22406621}.
• Pathway: Jak-STAT signaling pathway - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);JAK-STAT-Ncore;Androgen receptor signaling pathway;TGF-beta Signaling Pathway;sumoylation by ranbp2 regulates transcriptional repression;SUMOylation of DNA damage response and repair proteins;SUMOylation of transcription factors;IL12 signaling mediated by STAT4;SUMOylation of chromatin organization proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;SUMOylation;Sumoylation by RanBP2 regulates transcriptional repression (Consensus)

Recessive Scores

• pRec: 0.287

Intolerance Scores

• loftool: 0.184
• rvis_EVS: -0.43
• rvis_percentile_EVS: 25.37

Haploinsufficiency Scores

• pHI: 0.982
• hipred: Y
• hipred_score: 0.748
• ghis: 0.578

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.993

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pias2
• Phenotype: skeleton phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; vision/eye phenotype; reproductive system phenotype; pigmentation phenotype; cellular phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: protein sumoylation;androgen receptor signaling pathway;positive regulation of transcription, DNA-templated;negative regulation of androgen receptor signaling pathway
• Cellular component: nucleus;nucleoplasm;PML body;nuclear speck
• Molecular function: DNA binding;transcription coactivator activity;protein binding;transcription factor binding;zinc ion binding;SUMO transferase activity;ubiquitin protein ligase binding;androgen receptor binding;SUMO ligase activity