PIAS1
protein-codingprotein inhibitor of activated STAT 1, the group of Zinc fingers MIZ-type
Gene summary
This gene encodes a member of the protein inhibitor of activated STAT (PIAS) family. PIAS proteins function as SUMO E3 ligases and play important roles in many cellular processes by mediating the sumoylation of target proteins. This protein plays a central role as a transcriptional coregulator of numerous cellular pathways includign the STAT1 and nuclear factor kappaB pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
- DDXBP1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~144.3 kbGenCC 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 PIAS1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016166.3. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 19 | 6 | 25 | |||
| missense | 1 | 65 | 1 | 67 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 1 | 70 | 20 | 6 | 97 |
Highest pathogenic variant AF is 0.0000130129265
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057250.1 | 14 | MANE Select | |
| Ensembl | ENSP00000249636.6 | 14 | MANE Select | |
| RefSeq | NP_001307616.1 | 14 | Standard | |
| Ensembl | ENSP00000438574.1 | 14 | Standard |
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)
- Hepatitis C - Homo sapiens (human)
- TGF-Ncore
- JAK-STAT-Ncore
Biological Process
- G1/S transition of mitotic cell cycle
- negative regulation of transcription by RNA polymerase II
- JAK-STAT cascade
- spermatogenesis
- visual learning
Molecular Function
- DNA binding
- transcription coactivator activity
- transcription corepressor activity
- protein binding
- protein C-terminus binding
Cellular Component
- nucleus
- nucleoplasm
- PML body
- nuclear speck
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000249636
- Coding exons
- 14
- Length
- 136580
- Individuals with no LoFs
- 124639
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 124641
- p
- 0.00000802
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.72 | 205 | 348 | 0.589 | 0.0000182 | 4245 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.315
Intolerance Scores
- LoFtool
- 0.0548
- RVIS EVS
- -0.51
- RVIS percentile EVS
- 21.41
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.972
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |