HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PIK3R2
phosphoinositide-3-kinase regulatory subunit 2
Chromosome 19 Β· 19p13.11
NCBI Gene: 5296Ensembl: ENSG00000105647.21HGNC: HGNC:8980UniProt: O00459
245PubMed Papers
21Diseases
24Drugs
16Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneTransporter
RESEARCH IMPACT
Trending
CLINICAL
Clinical TrialsOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
phosphatidylinositol 3-kinase/protein kinase B signal transductionreceptor tyrosine kinase bindingregulation of autophagyphosphotyrosine residue bindingMegalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalusmegalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1cancerovergrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
✦AI Summary

PIK3R2 (phosphoinositide-3-kinase regulatory subunit 2) functions as a regulatory subunit of the phosphoinositide-3-kinase (PI3K) complex that phosphorylates phosphatidylinositol 4,5-bisphosphate to generate PIP3, a crucial second messenger in cellular signaling 1. Unlike its paralog PIK3R1 which acts as a tumor suppressor, PIK3R2 functions as an oncogene and is frequently overexpressed in various cancers 23. The protein promotes cell proliferation, survival, and growth through activation of the PI3K/AKT signaling pathway 45. PIK3R2 can interact with phosphorylated EphA2 to facilitate downstream GSK3Ξ²/Ξ²-catenin signaling and promote epithelial-mesenchymal transition in cancer cells 6. Activating mutations in PIK3R2, particularly the recurrent p.G373R mutation, cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome, characterized by brain overgrowth, seizures, and developmental abnormalities 178. The p.G373R mutation results in PI3K pathway hyperactivation, leading to increased cell size rather than cell number in affected brain tissue 7. PIK3R2 also serves as a target for miR-126-3p regulation and plays roles in angiogenesis and cell survival 5.

Sources cited
1
PIK3R2 functions in PI3K complex and recurrent G373R mutation causes MPPH syndrome
PMID: 22729224
2
PIK3R2 acts as oncogene, unlike PIK3R1 which is tumor suppressor
PMID: 30961830
3
PIK3R2 is highly expressed in most tumors and associated with poor prognosis
PMID: 35395865
4
PIK3R2 p.G373R mutation causes brain overgrowth through PI3K pathway hyperactivation
PMID: 32856318
5
PIK3R2 is frequently implicated in polymicrogyria cases
PMID: 37486637
6
PIK3R2 interacts with phosphorylated EphA2 and promotes EMT through GSK3Ξ²/Ξ²-catenin signaling
PMID: 39702326
7
PIK3R2 is targeted by miR-126-3p and involved in PI3K/AKT/mTOR pathway
PMID: 35883161
8
PIK3R2 promotes cell proliferation and activates PI3K/AKT signaling in colon cancer
PMID: 37090079
Disease Associationsβ“˜21
Megalencephaly - polymicrogyria - postaxial polydactyly - hydrocephalusOpen Targets
0.79Strong
megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1Open Targets
0.77Strong
cancerOpen Targets
0.58Moderate
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genesOpen Targets
0.46Moderate
SeizureOpen Targets
0.44Moderate
genetic disorderOpen Targets
0.42Moderate
breast cancerOpen Targets
0.41Moderate
non-small cell lung carcinomaOpen Targets
0.40Weak
neurodegenerative diseaseOpen Targets
0.37Weak
multiple myelomaOpen Targets
0.37Weak
megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndromeOpen Targets
0.37Weak
Alzheimer diseaseOpen Targets
0.35Weak
lysosomal storage diseaseOpen Targets
0.35Weak
multiple sclerosisOpen Targets
0.35Weak
Parkinson diseaseOpen Targets
0.35Weak
Intellectual disabilityOpen Targets
0.34Weak
megalencephaly-capillary malformation-polymicrogyria syndromeOpen Targets
0.33Weak
infectionOpen Targets
0.28Weak
head and neck malignant neoplasiaOpen Targets
0.28Weak
Respiratory tract infectionOpen Targets
0.26Weak
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1UniProt
Pathogenic Variants16
NM_005027.4(PIK3R2):c.1117G>A (p.Gly373Arg)Pathogenic
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1|Inborn genetic diseases|not provided|Megalencephaly-capillary malformation-polymicrogyria syndrome|Intellectual disability|Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes|Seizure|PIK3R2-related disorder|Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome
β˜…β˜…β˜…β˜†2022β†’ Residue 373
NM_005027.4(PIK3R2):c.1126A>G (p.Lys376Glu)Pathogenic
not provided|Seizure|Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1|PIK3R2-related disorder
β˜…β˜…β˜†β˜†2023β†’ Residue 376
NM_005027.4(PIK3R2):c.1669G>T (p.Asp557Tyr)Pathogenic
Seizure|not provided|PIK3R2-related disorder
β˜…β˜…β˜†β˜†2023β†’ Residue 557
NM_005027.4(PIK3R2):c.1669G>C (p.Asp557His)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 557
NM_005027.4(PIK3R2):c.598+2T>GLikely pathogenic
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
β˜…β˜†β˜†β˜†2024
NM_005027.4(PIK3R2):c.1681A>G (p.Asn561Asp)Likely pathogenic
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
β˜…β˜†β˜†β˜†2022β†’ Residue 561
NM_005027.4(PIK3R2):c.988T>G (p.Trp330Gly)Likely pathogenic
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
β˜…β˜†β˜†β˜†2020β†’ Residue 330
NM_005027.4(PIK3R2):c.1056C>G (p.Phe352Leu)Likely pathogenic
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
β˜…β˜†β˜†β˜†2018β†’ Residue 352
NM_005027.4(PIK3R2):c.1359C>A (p.Tyr453Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2018β†’ Residue 453
NM_005027.4(PIK3R2):c.598+1G>APathogenic
not provided
β˜…β˜†β˜†β˜†2016
NM_005027.4(PIK3R2):c.1690A>G (p.Lys564Glu)Pathogenic
not provided
β˜…β˜†β˜†β˜†2016β†’ Residue 564
NM_005027.4(PIK3R2):c.1948A>G (p.Ser650Gly)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2015β†’ Residue 650
NM_005027.4(PIK3R2):c.1153G>A (p.Gly385Arg)Pathogenic
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
β˜†β˜†β˜†β˜†2020β†’ Residue 385
NM_005027.4(PIK3R2):c.572C>A (p.Ser191Ter)Likely pathogenic
Multiple myeloma
β˜†β˜†β˜†β˜†2019β†’ Residue 191
NM_005027.4(PIK3R2):c.850G>A (p.Val284Met)Likely pathogenic
Multiple myeloma
β˜†β˜†β˜†β˜†2019β†’ Residue 284
NM_005027.4(PIK3R2):c.1202T>C (p.Leu401Pro)Pathogenic
Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1
β˜†β˜†β˜†β˜†2014β†’ Residue 401
View on ClinVar β†—
Drug Targets24
APITOLISIBPhase II
PI3-kinase class I inhibitor
non-Hodgkins lymphoma
AZD-6482Phase I
PI3-kinase class I inhibitor
BGT-226Phase I/II
PI3-kinase class I inhibitor
BUPARLISIBPhase III
PI3-kinase class I inhibitor
breast cancer
DACTOLISIBPhase III
PI3-kinase class I inhibitor
Respiratory tract infection
DS-7423Phase I
Serine/threonine-protein kinase mTOR inhibitor
GEDATOLISIBPhase III
PI3-kinase class I inhibitor
breast cancer
GSK-1059615Phase I
PI3-kinase class I inhibitor
breast cancer
IZORLISIBPhase I/II
PI3-kinase class I inhibitor
colorectal cancer
OMIPALISIBPhase I
PI3-kinase class I inhibitor
lymphoma
PANULISIBPhase I
PI3-kinase class I inhibitor
PAXALISIBPhase II
PI3-kinase class I inhibitor
brain glioblastoma
PF-04691502Phase II
PI3-kinase class I inhibitor
endometrial cancer
PICTILISIBPhase II
PI3-kinase class I inhibitor
breast cancer
PILARALISIBPhase II
PI3-kinase class I inhibitor
RECILISIBPhase I
PI3-kinase class I inhibitor
SAMOTOLISIBPhase II
PI3-kinase class I inhibitor
prostate cancer
SF-1126Phase II
PI3-kinase class I inhibitor
head and neck malignant neoplasia
SONOLISIBPhase II
PI3-kinase class I inhibitor
TASELISIBPhase III
PI3-kinase class I inhibitor
breast cancer
VOXTALISIBPhase II
Serine/threonine-protein kinase mTOR inhibitor
VS-5584Phase I
Serine/threonine-protein kinase mTOR inhibitor
Malignant Mesothelioma
WX-037Phase I
PI3-kinase class I inhibitor
neoplasm
ZSTK-474Phase I
PI3-kinase class I inhibitor
Related Genes
PIK3CBProtein interaction100%PIK3CDProtein interaction100%PIK3CAProtein interaction100%PIK3CGProtein interaction100%EGFRProtein interaction99%IRS1Protein interaction99%
Tissue Expression6 tissues
Liver
100%
Ovary
94%
Brain
84%
Lung
44%
Bone Marrow
28%
Heart
0%
Gene Interaction Network
Click a node to explore
PIK3R2PIK3CBPIK3CDPIK3CAPIK3CGEGFRIRS1
PROTEIN STRUCTURE
Preparing viewer…
PDB7RNU Β· 1.45 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.76LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.58 [0.45–0.76]
RankingsWhere PIK3R2 stands among ~20K protein-coding genes
  • #1,586of 20,598
    Most Researched245 Β· top 10%
  • #2,382of 5,498
    Most Pathogenic Variants16
  • #6,078of 17,882
    Most Constrained (LOEUF)0.76
Genes detectedPIK3R2
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.
PMID: 22729224
Nat Genet Β· 2012
1.00
2
SNAI1 promotes epithelial-mesenchymal transition and maintains cancer stem cell-like properties in thymic epithelial tumors through the PIK3R2/p-EphA2 Axis.
PMID: 39702326
J Exp Clin Cancer Res Β· 2024
0.90
3
Exome Sequencing and the Identification of New Genes and Shared Mechanisms in Polymicrogyria.
PMID: 37486637
JAMA Neurol Β· 2023
0.80
4
Intraplatelet miRNA-126 regulates thrombosis and its reduction contributes to platelet inhibition.
PMID: 38900927
Cardiovasc Res Β· 2024
0.76
5
The Opposing Roles of PIK3R1/p85Ξ± and PIK3R2/p85Ξ² in Cancer.
PMID: 30961830
Trends Cancer Β· 2019
0.70