PIK3R1 Gene (Phosphoinositide-3-Kinase Regulatory Subunit 1)
Key regulator of PI3K signaling in growth, metabolism, and cancer
Gene Information Card
| Symbol | PIK3R1 |
|---|---|
| Full Name | Phosphoinositide-3-kinase regulatory subunit 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q13.1 |
| NCBI Gene ID | 5295 ncbi.nlm.nih.gov/gene/5295 |
| Ensembl ID | ENSG00000145675 |
| UniProt ID | P27986 |
| OMIM ID | 171833 |
| HGNC ID | 8980 |
| Aliases | GRB1, p85-alpha, p85, PI3K regulatory subunit alpha |
Description
PIK3R1 encodes the p85α regulatory subunit of class IA phosphoinositide 3-kinase (PI3K). This subunit binds to and stabilizes the p110 catalytic subunit, mediating activation by receptor tyrosine kinases through its SH2 domains. PIK3R1 is critical for PI3K/AKT signaling, regulating cell growth, proliferation, survival, and metabolism. Mutations in PIK3R1 are associated with immunodeficiency, insulin resistance, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| SHORT syndrome | Loss-of-function mutations in PIK3R1 disrupt PI3K signaling, leading to short stature, hyperextensibility, ocular depression, Rieger anomaly, and teething delay. | OMIM #269880 |
| Agammaglobulinemia 7, autosomal recessive | Biallelic mutations impair B-cell development and antibody production. | OMIM #615214 |
| PIK3R1 deficiency with immunodeficiency | Homozygous or compound heterozygous mutations cause combined immunodeficiency with recurrent infections. | ClinVar, NCBI |
| Breast cancer | Somatic mutations (e.g., R348*) lead to constitutive PI3K activation. | COSMIC, NCBI |
| Colorectal cancer | Amplifications and missense mutations in PIK3R1 contribute to tumorigenesis. | COSMIC |
| Endometrial cancer | Recurrent mutations in the iSH2 domain (e.g., N564K) promote oncogenic signaling. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 38.2 | Medium |
| Breast | 25.1 | Medium |
| Lung | 22.8 | Medium |
| Brain | 15.3 | Low |
| Liver | 12.7 | Low |
| Skeletal muscle | 10.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 42.1 | High expression |
| HeLa | 35.6 | High expression |
| MCF7 | 28.4 | Medium expression |
| A549 | 22.0 | Medium expression |
| K562 | 18.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R348* | Nonsense | 0.5 | Truncation, loss of SH2 domain, gain-of-function in PI3K signaling |
| N564K | Missense | 0.3 | Disrupts inhibitory interaction with p110, constitutive activation |
| D560Y | Missense | 0.2 | Impaired SH2 domain, altered signaling |
| c.1425+1G>A | Splice site | 0.1 | Exon skipping, loss of function in immunodeficiency |
| E439del | Deletion | 0.1 | In-frame deletion, reduced p85-p110 binding |
Mutation functional classification
Loss of Function (LOF)
Biallelic loss-of-function mutations (e.g., splice site, nonsense) cause immunodeficiency and SHORT syndrome by impairing PI3K signaling in immune and developmental pathways.
Gain of Function (GOF)
Somatic missense mutations (e.g., N564K, R348*) in the iSH2 domain disrupt autoinhibition, leading to constitutive PI3K activation and oncogenic transformation.
Dominant Negative (DN)
Some mutations (e.g., D560Y) produce a p85 subunit that binds p110 but fails to activate it, suppressing normal PI3K signaling in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
Pathways
• PI3K-Akt signaling pathway (KEGG hsa04151)
• Insulin signaling pathway (KEGG hsa04910)
• ErbB signaling pathway (KEGG hsa04012)
• Fc gamma R-mediated phagocytosis (KEGG hsa04666)
• B cell receptor signaling pathway (KEGG hsa04662)
• mTOR signaling pathway (Reactome R-HSA-165159)
Protein Summary
The p85α regulatory subunit encoded by PIK3R1 contains an N-terminal SH3 domain, a BH domain, and two SH2 domains flanking an inter-SH2 (iSH2) domain that mediates binding to the p110 catalytic subunit. It functions as an adaptor that recruits PI3K to activated receptor tyrosine kinases, enabling lipid kinase activity and generation of PIP3. The protein also has a role in insulin signaling and cytoskeletal organization. Mutations in the iSH2 domain are common in cancer, while loss-of-function variants cause primary immunodeficiency syndromes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PIK3R1 Knockout HEK293T Cell Line | EDJ-KQ159 | Human | 5295 | Details Get a Quote |
| PIK3R1 Knockout HEK293 Cell Line | EDJ-KQ520 | Human | 5295 | Details Get a Quote |
| PIK3R1 Knockout A-549 Cell Line | EDJ-KQ18855 | Human | 5295 | Details Get a Quote |
| PIK3R1 Knockout HCT 116 Cell Line | EDJ-KQ18856 | Human | 5295 | Details Get a Quote |
| PIK3R1 Knockout HeLa Cell Line | EDJ-KQ18857 | Human | 5295 | Details Get a Quote |
| Pik3r1 Knockout RAW 264.7 Cell Line | EDJ-KZ4 | Mouse | 18708 | Details Get a Quote |
| PIK3R1 Knockout HAP1 Cell Line | EDC07888 | Human | 5295 | Details Get a Quote |
| PIK3R1 (p.Y73=) Point Mutation in HAP1 Cell Line | EDC03579 | Human | 5295 | Details Get a Quote |
