PIK3R3
protein-codingphosphoinositide-3-kinase regulatory subunit 3, the group of SH2 domain containing
Gene summary
Phosphatidylinositol 3-kinase (PI3K) phosphorylates phosphatidylinositol and similar compounds, which then serve as second messengers in growth signaling pathways. PI3K is composed of a catalytic and a regulatory subunit. The protein encoded by this gene represents a regulatory subunit of PI3K. The encoded protein contains two SH2 domains through which it binds activated protein tyrosine kinases to regulate their activity. [provided by RefSeq, Jun 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~92.9 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 PIK3R3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003629.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 53 | 53 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 54 | 0 | 0 | 54 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003620.3 | 10 | MANE Select | |
| Ensembl | ENSP00000262741.5 | 10 | MANE Select | |
| RefSeq | NP_001107644.1 | 10 | Standard | |
| RefSeq | NP_001290357.1 | 11 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- PI3K-Akt signaling pathway - Homo sapiens (human)
- Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
- Non-small cell lung cancer - Homo sapiens (human)
- Platelet activation - Homo sapiens (human)
- Chronic myeloid leukemia - Homo sapiens (human)
Biological Process
- positive regulation of protein phosphorylation
- cell migration involved in sprouting angiogenesis
- insulin receptor signaling pathway
- positive regulation of gene expression
- positive regulation of cell migration
Molecular Function
- phosphotyrosine residue binding
- protein binding
- 1-phosphatidylinositol-3-kinase activity
- 1-phosphatidylinositol-3-kinase regulator activity
Cellular Component
- cytosol
- phosphatidylinositol 3-kinase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000262741
- Coding exons
- 10
- Length
- 136349
- Individuals with no LoFs
- 125675
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 73
- Defined
- 125748
- p
- 0.000290
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0444 | 248 | 250 | 0.992 | 0.0000126 | 3073 |
| Missense (PolyPhen) | 88 | 87.886 | 1.0013 | 1058 | ||
| Synonymous | 1.59 | 67 | 85.8 | 0.781 | 0.00000409 | 784 |
| Loss of Function | 1.54 | 19 | 27.8 | 0.684 | 0.00000159 | 315 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.00021 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.000049 | 0.000046 | rare |
| European (Non-Finnish) | 0.00036 | 0.00036 | rare |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0.00051 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds to activated (phosphorylated) protein-tyrosine kinases through its SH2 domain and regulates their kinase activity. During insulin stimulation, it also binds to IRS-1.;
Recessive Scores
- pRec
- 0.342
Intolerance Scores
- LoFtool
- 0.485
- RVIS EVS
- -0.09
- RVIS percentile EVS
- 46.74
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.961
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |