PIAS3

Chr 1

protein inhibitor of activated STAT 3

Also known as: ZMIZ5

NCBI Gene: 10401ENSG00000131788UniProt: Q9Y6X2

This gene encodes a member of the PIAS [protein inhibitor of activated STAT (signal transducer and activator of transcription)] family of transcriptional modulators. The protein functions as a SUMO (small ubiquitin-like modifier)-E3 ligase which catalyzes the covalent attachment of a SUMO protein to specific target substrates. It directly binds to several transcription factors and either blocks or enhances their activity. Alternatively spliced transcript variants of this gene have been identified, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

0
ClinVar variants
0
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PIAS3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.30LOEUF
pLI 0.985
Z-score 4.43
OE 0.13 (0.06–0.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.00Z-score
OE missense 0.85 (0.77–0.94)
298 obs / 350.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.13 (0.06–0.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.77–0.94)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.11
0≤1.21.6
LoF obs/exp: 4 / 30.4Missense obs/exp: 298 / 350.9Syn Z: -1.01

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

PIAS3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
METTL10-Mediated PIAS3 Methylation Links Purine Metabolism to Gastric Cancer Progression.
Tan J et al.·Adv Sci (Weinh)
2025
PIAS3-mediated feedback loops promote chronic colitis-associated malignant transformation.
Ma J et al.·Theranostics
2018
Obesity-induced extracellular vesicles proteins drive the endometrial cancer pathogenesis: therapeutic potential of HO-3867 and Metformin.
Sakaue T et al.·Oncogene
2024
Ubiquitin-proteasome Pathway-linked Gene Signatures as Prognostic Indicators in Prostate Cancer.
Takashima Y et al.·Anticancer Res
2025
TRIM8 regulates stemness in glioblastoma through PIAS3-STAT3.
Zhang C et al.·Mol Oncol
2017
Upregulation of tumor suppressor PIAS3 by Honokiol promotes tumor cell apoptosis via selective inhibition of STAT3 tyrosine 705 phosphorylation.
Fei Y et al.·J Nat Med
2024
Association of Selected STAT Inhibitors with Prolactin-Induced Protein (PIP) in Breast Cancer.
Jabłońska K et al.·Int J Mol Sci
2025
MicroRNA-199a-5p promotes tumour growth by dual-targeting PIAS3 and p27 in human osteosarcoma.
Wang C et al.·Sci Rep
2017
Protein Inhibitor of Activated STAT3 (PIAS3) Is Down-Regulated in Eutopic Endometrium of Women with Endometriosis.
Yoo JY et al.·Biol Reprod
2016
Targeting JAK/STAT signaling pathway by curcumin: implications for spinal cord injury neuroprotection.
Abroumand Gholami A et al.·Inflammopharmacology
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools