PIAS2

Chr 18

protein inhibitor of activated STAT 2

Also known as: ARIP3, DIP, MIZ1, PIASX, SIZ2, ZMIZ4

The protein functions as a SUMO E3 ligase that regulates gene expression by promoting sumoylation of target proteins including p53, c-Jun, and steroid hormone receptors. Mutations cause neurodevelopmental disorders with intellectual disability and developmental delay, following an autosomal dominant inheritance pattern. This gene is highly constrained against loss-of-function variants, indicating that even single functional copies are critical for normal development.

Summary from RefSeq, UniProt
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0
Active trials
5
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.25
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryPIAS2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.25LOEUF
pLI 0.997
Z-score 4.61
OE 0.10 (0.040.25)
Highly constrained

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

Missense Constraint
2.06Z-score
OE missense 0.68 (0.610.76)
226 obs / 331.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.040.25)
00.351.4
Missense OE0.68 (0.610.76)
00.61.4
Synonymous OE0.89
01.21.6
LoF obs/exp: 3 / 30.5Missense obs/exp: 226 / 331.4Syn Z: 0.95
DN
0.3991th %ile
GOF
0.2099th %ile
LOF
0.76top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.25

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PIAS2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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