GeneBe

PIAS4

protein-coding

protein inhibitor of activated STAT 4, the group of Zinc fingers MIZ-type

Gene summary

Enables SUMO ligase activity and ubiquitin protein ligase binding activity. Involved in several processes, including negative regulation of protein localization to chromatin; positive regulation of double-strand break repair via homologous recombination; and regulation of RNA metabolic process. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_015897.4

Inheritance

—

ClinVar variants

U:73B:18

Top phenotype

PIAS4-related disorder

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr19:4,007,736-4,039,386

External References & Databases

Ensembl (ENSG00000105229)NCBI Gene (51588)OMIM (605989)HGNC:17002GenCCUniProt (Q8N2W9)AlphaFoldClinVar (PIAS4)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~31.7 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PIAS4 variants in ClinVar

3 Conditions Cataloged
not specifiedTotal: 70
not providedTotal: 10
PIAS4-related disorderTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015897.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
12
clinvar
2
clinvar
 15
missense
70
clinvar
4
clinvar
 74
nonsense
0
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
2
clinvar
 2
Total007316291
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_015897.4RefSeqNP_056981.211MANE Select
ENST00000262971.3EnsemblENSP00000262971.111MANE Select
ENST00000862888.1EnsemblENSP00000532947.111Standard
ENST00000862888.2EnsemblENSP00000532947.111Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Jak-STAT signaling pathway - Homo sapiens (human)
  • Ubiquitin mediated proteolysis - Homo sapiens (human)
  • Fluid shear stress and atherosclerosis - Homo sapiens (human)
  • NF-kappa B signaling pathway - Homo sapiens (human)
  • TGF-Ncore

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • double-strand break repair via nonhomologous end joining
  • negative regulation of tumor necrosis factor-mediated signaling pathway
  • Wnt signaling pathway
  • protein sumoylation

Molecular Function

  • DNA binding
  • transcription corepressor activity
  • protein binding
  • protein C-terminus binding
  • zinc ion binding

Cellular Component

  • nucleus
  • nucleoplasm
  • cytoplasm
  • nuclear matrix
  • PML body

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000262971
Coding exons
11
Length
31741
Individuals with no LoFs
117428
Homozygous LoFs
0
Heterozygous LoFs
1
Defined
117429
p
0.00000426
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.632093470.6030.00002443277
Missense (PolyPhen)48142.160.337661325
Synonymous-1.811951651.180.00001351018
Loss of Function4.66025.30.000.00000114295

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000670.000067rare
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)00.0absent
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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/TP53 pathway, the Wnt pathway and the steroid hormone signaling pathway. Involved in gene silencing. Mediates sumoylation of CEBPA, PARK7, HERC2, MYB, TCF4 and RNF168. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations. Enhances the sumoylation of MTA1 and may participate in its paralog-selective sumoylation. {ECO:0000269|PubMed:12511558, ECO:0000269|PubMed:12631292, ECO:0000269|PubMed:12727872, ECO:0000269|PubMed:15831457, ECO:0000269|PubMed:15976810, ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:22508508}.;

Recessive Scores

pRec
0.167

Intolerance Scores

RVIS EVS
-0.69
RVIS percentile EVS
15.27

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.962

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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