PIK3R1 Gene

HGNC Family	SH2 domain containing
Name	phosphoinositide-3-kinase, regulatory subunit 1 (alpha)
Description	Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The enzyme comprises a 110 kD catalytic subunit and a regulatory subunit of either 85, 55, or 50 kD. This gene encodes the 85 kD regulatory subunit. Phosphatidylinositol 3-kinase plays an important role in the metabolic actions of insulin, and a mutation in this gene has been associated with insulin resistance. Alternative splicing of this gene results in four transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPIK3R1 encodes the regulatory p85α subunit of class IA phosphatidylinositol 3‐kinases (PI3K) and is a central coordinator of PI3K signaling. p85α stabilizes the catalytic p110 subunits by direct binding through its nSH2, iSH2, and cSH2 domains, and it normally restrains PI3K activity through inhibitory contacts. Structural analyses have shown that cancer‐associated mutations in PIK3R1 disrupt these inter‐domain interactions, resulting in loss of inhibitory control and consequent hyperactivation of the PI3K–Akt pathway. In addition, p85α directly interacts with the lipid phosphatase PTEN, enhancing its phosphatase activity and thereby influencing the balance between phosphatidylinositol 3,4,5–trisphosphate production and degradation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAlterations in PIK3R1 are implicated in a wide spectrum of human diseases. Somatic mutations in this gene have been identified in endometrial, colon, glioblastoma, and breast cancers, where the loss or mutation of key p85α domains abrogates its inhibitory function toward p110 isoforms, thereby promoting constitutive PI3K–Akt activation, increased cell proliferation, migration, and survival. In metabolic disorders and developmental syndromes such as type 2 diabetes and SHORT syndrome, germline or common variants in PIK3R1 have been associated with insulin resistance and growth defects. Moreover, microRNAs including miR‑21, miR‑503, and miR‑486–5p have been shown to target PIK3R1, further modulating its expression and impacting tumor progression, stromal interactions, and clinical outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its well‐defined roles in tumorigenesis and metabolic regulation, PIK3R1 is also critical for modulating immune responses and other receptor‐mediated signaling processes. In stem and immune cell compartments, splice–site mutations in PIK3R1 are responsible for immunodeficiency syndromes such as activated PI3K–delta syndrome (APDS), where dysregulated p85α fails to properly restrain p110 activity. p85α is further recruited to activated receptors via adaptor proteins – for instance, through interactions with CD133 in glioma stem cells, with IRS proteins in platelets upon IGF‑1 stimulation, and with components of the cytoskeletal machinery such as WAVE3 – thereby linking extracellular signals to PI3K–Akt activation. Moreover, signals from innate immune receptors (via TLR5/MyD88) and TGF‑β receptors modulate the ubiquitylation and membrane recruitment of p85α, and recent data indicate that phosphorylation events (e.g., on key metabolic enzymes) can trigger p85α binding in positive feedback loops controlling glycolysis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chuan-Hsiang Huang, Diana Mandelker, Oleg Schmidt-Kittler, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "TGF-β promotes PI3K-AKT signaling and prostate cancer cell migration through the TRAF6-mediated ubiquitylation of p85α."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.aal4186"}], "href": "https://doi.org/10.1126/scisignal.aal4186"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28676490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28676490"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Li Chen, Liu Yang, Ling Yao, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "EGFR-Phosphorylated Platelet Isoform of Phosphofructokinase 1 Promotes PI3K Activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2018.03.018"}], "href": "https://doi.org/10.1016/j.molcel.2018.03.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29677490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29677490"}]}]}]}
Synonyms	GRB1, AGM7, p85, IMD36, P85-ALPHA
Proteins	P85A_HUMAN
NCBI Gene ID	5295
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

PIK3R1 has 15,860 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 152 datasets.

Click the + buttons to view associations for PIK3R1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

PIK3R1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by PIK3R1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PIK3R1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of PIK3R1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of PIK3R1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of PIK3R1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of PIK3R1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of PIK3R1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving PIK3R1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of PIK3R1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PIK3R1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of PIK3R1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of PIK3R1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of PIK3R1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of PIK3R1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with PIK3R1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with PIK3R1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with PIK3R1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of PIK3R1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of PIK3R1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of PIK3R1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with PIK3R1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with PIK3R1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing PIK3R1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of PIK3R1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing PIK3R1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing PIK3R1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing PIK3R1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with PIK3R1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with PIK3R1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing PIK3R1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of PIK3R1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with PIK3R1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with PIK3R1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with PIK3R1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of PIK3R1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by PIK3R1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DEPOD Substrates of Phosphatases	phosphatases that dephosphorylate PIK3R1 protein from the curated DEPOD Substrates of Phosphatases dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving PIK3R1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with PIK3R1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with PIK3R1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.