PIAS1

protein inhibitor of activated STAT 1, the group of Zinc fingers MIZ-type

Basic information

Region (hg38): 15:68054309-68198603

Previous symbols: [ "DDXBP1" ]

Links

ENSG00000033800 ∙ NCBI:8554 ∙ OMIM:603566 ∙ HGNC:2752 ∙ Uniprot:O75925 ∙ 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 PIAS1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIAS1 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				13	6	19
missense			29	1		30
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1	1	2
non coding				3	16	19
Total	0	0	30	17	22

Variants in PIAS1

This is a list of pathogenic ClinVar variants found in the PIAS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-68054335-C-T			Likely benign (Apr 04, 2023)
15-68086356-C-T			Likely benign (Sep 05, 2024)
15-68086359-C-T			Benign (Dec 09, 2017)
15-68086458-A-C		not specified	Uncertain significance (Nov 13, 2023)
15-68086518-C-T			Benign (Jan 13, 2024)
15-68086561-A-G		not specified	Uncertain significance (Dec 04, 2021)
15-68086571-T-A		not specified	Uncertain significance (Dec 23, 2022)
15-68086581-T-G		not specified	Uncertain significance (Jan 23, 2024)
15-68086588-C-A			Uncertain significance (Sep 25, 2022)
15-68086593-A-C			Likely benign (Sep 27, 2023)
15-68086598-C-T		Nephronophthisis	Likely pathogenic (Dec 23, 2015)
15-68086599-G-A			Benign (Jul 09, 2021)
15-68086677-C-G			Benign (Mar 31, 2023)
15-68086683-G-A			Likely benign (Jul 29, 2021)
15-68141758-TTTG-T			Benign (May 26, 2021)
15-68141874-T-TG			Benign (May 14, 2021)
15-68141938-T-G			Benign (Aug 24, 2023)
15-68142029-A-G		not specified	Uncertain significance (Nov 12, 2024)
15-68142041-G-C			Benign (Jan 23, 2025)
15-68145923-G-GT			Benign (Aug 02, 2021)
15-68146072-C-A			Benign (May 26, 2021)
15-68146552-C-T			Likely benign (Feb 26, 2024)
15-68146567-G-T			Uncertain significance (Nov 06, 2022)
15-68146593-G-A		not specified	Uncertain significance (Dec 05, 2022)
15-68146632-T-A		not specified	Uncertain significance (Jan 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIAS1	protein_coding	protein_coding	ENST00000249636	14	136580

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000124	124639	0	2	124641	0.00000802

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.72	205	348	0.589	0.0000182	4245
Missense in Polyphen		61	153.06	0.39853		1825
Synonymous	-1.58	157	134	1.17	0.00000763	1281
Loss of Function	5.22	0	31.8	0.00	0.00000176	388

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.0000993	0.0000993
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 pathway and the steroid hormone signaling pathway. In vitro, binds A/T-rich DNA. The effects of this transcriptional coregulation, transactivation or silencing, may vary depending upon the biological context. Together with PRMT1, may repress STAT1 transcriptional activity, in the late phase of interferon gamma (IFN-gamma) signaling. Sumoylates PML (at'Lys-65' and 'Lys-160') and PML-RAR and promotes their ubiquitin-mediated degradation. PIAS1-mediated sumoylation of PML promotes its interaction with CSNK2A1/CK2 which in turn promotes PML phosphorylation and degradation (By similarity). Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation. Plays a dynamic role in adipogenesis by promoting the SUMOylation and degradation of CEBPB (By similarity). {ECO:0000250|UniProtKB:O88907, ECO:0000269|PubMed:14500712, ECO:0000269|PubMed:19136629, ECO:0000269|PubMed:21965678}.
• Pathway: Jak-STAT signaling pathway - Homo sapiens (human);Ubiquitin mediated proteolysis - Homo sapiens (human);Hepatitis C - Homo sapiens (human);TGF-Ncore;JAK-STAT-Ncore;Androgen receptor signaling pathway;Interleukin-11 Signaling Pathway;Mesodermal Commitment Pathway;TGF-beta Signaling Pathway;The human immune response to tuberculosis;Interferon type I signaling pathways;DNA Repair;sumoylation by ranbp2 regulates transcriptional repression;Cytokine Signaling in Immune system;SUMOylation of DNA damage response and repair proteins;SUMOylation of transcription factors;SUMOylation of chromatin organization proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;Regulation of IFNG signaling;Immune System;SUMOylation;Coregulation of Androgen receptor activity;Signaling events mediated by TCPTP;IL11;Interferon gamma signaling;IFN-gamma pathway;Formation of Incision Complex in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Interferon Signaling;Sumoylation by RanBP2 regulates transcriptional repression;Hedgehog signaling events mediated by Gli proteins;IL6-mediated signaling events;Nucleotide Excision Repair (Consensus)

Recessive Scores

• pRec: 0.315

Intolerance Scores

• loftool: 0.0548
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.41

Haploinsufficiency Scores

• pHI: 0.971
• hipred: Y
• hipred_score: 0.739
• ghis: 0.617

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.972

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pias1
• Phenotype: growth/size/body region phenotype; immune 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)

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;negative regulation of transcription by RNA polymerase II;JAK-STAT cascade;spermatogenesis;visual learning;protein sumoylation;androgen receptor signaling pathway;positive regulation of proteasomal ubiquitin-dependent protein catabolic process;positive regulation of protein sumoylation;regulation of cell population proliferation;negative regulation of apoptotic process;fat cell differentiation;positive regulation of transcription, DNA-templated;positive regulation of smooth muscle cell differentiation;regulation of interferon-gamma-mediated signaling pathway;protein-DNA complex assembly
• Cellular component: nucleus;nucleoplasm;PML body;nuclear speck
• Molecular function: DNA binding;transcription coactivator activity;transcription corepressor activity;protein binding;protein C-terminus binding;zinc ion binding;SUMO transferase activity;enzyme binding;protein domain specific binding;ubiquitin protein ligase binding;androgen receptor binding;SUMO ligase activity