PIK3CA Gene Complete Identifier and Functional Mapping Reference
Provide a comprehensive cross-database identifier and functional mapping reference for human PIK3CA — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene PIK3CA, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene PIK3CA, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene PIK3CA protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene PIK3CA protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene PIK3CA, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene PIK3CA, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene PIK3CA, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene PIK3CA protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene PIK3CA, summarize transcription factor regulatory data. If PIK3CA is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate PIK3CA — names with evidence type (ChIP-seq / predicted / experimentally validated) If PIK3CA is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene PIK3CA protein as a drug target, summarize pharmacology data. If PIK3CA is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If PIK3CA is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene PIK3CA, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene PIK3CA, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in PIK3CA: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations
Executive summary
PIK3CA encodes the catalytic alpha subunit (p110α) of phosphatidylinositol 3-kinase, one of the most frequently mutated oncogenes in human cancer and a central node in PI3K/AKT signaling. The 1068-amino-acid protein is structurally well-characterized, with 125 PDB entries and an AlphaFold model scoring 92.5 pLDDT globally (83% of residues at very high confidence). Clinically, ~1,566 ClinVar variants have been catalogued, with hotspot mutations driving both Mendelian overgrowth syndromes — particularly megalencephaly-capillary malformation-polymicrogyria and the broader PIK3CA-related overgrowth spectrum — and sporadic cancers including breast, colorectal, and endometrial carcinoma. Three PI3Kα inhibitors are FDA-approved: alpelisib, copanlisib, and inavolisib; alpelisib alone has 96 registered clinical trials, with its approval specifically tied to PIK3CA-mutant HR+/HER2- breast cancer. The gene is ubiquitously expressed across 284 of 297 surveyed tissue conditions (max expression score 94.28), and engages ~4,602 high-confidence STRING interactions, with its tightest partners being the PI3K regulatory subunits PIK3R1–3 and downstream effectors AKT1–3.
Gene identifiers
HGNC: HGNC:8975 (PIK3CA) Ensembl: ENSG00000121879 NCBI Entrez: 5290 OMIM: 171834 Location (GRCh38): Chromosome 3, 179,148,114–179,240,093 (+strand)
Transcript identifiers
Ensembl Transcripts (15 total)
| Transcript ID | Biotype | Start | End |
|---|---|---|---|
| ENST00000263967 | protein_coding | 179148357 | 179240093 |
| ENST00000468036 | protein_coding | 179149527 | 179199179 |
| ENST00000477735 | protein_coding | 179148114 | 179198888 |
| ENST00000643187 | protein_coding | 179148574 | 179235098 |
| ENST00000876545 | protein_coding | 179148589 | 179235137 |
| ENST00000913499 | protein_coding | 179148177 | 179237493 |
| ENST00000913500 | protein_coding | 179148428 | 179235325 |
| ENST00000955189 | protein_coding | 179148186 | 179235121 |
| ENST00000955190 | protein_coding | 179148256 | 179235120 |
| ENST00000462255 | retained_intron | 179218209 | 179235016 |
| ENST00000674534 | retained_intron | 179202977 | 179235084 |
| ENST00000675467 | retained_intron | 179196019 | 179235371 |
| ENST00000675796 | retained_intron | 179226882 | 179235107 |
| ENST00000674622 | nonsense_mediated_decay | 179210524 | 179235084 |
| ENST00000675786 | nonsense_mediated_decay | 179149001 | 179235084 |
RefSeq mRNA Transcripts (3 total, human)
| mRNA ID | Gene Symbol | Status | MANE Select |
|---|---|---|---|
| NM_006218 | PIK3CA | REVIEWED | ✓ |
| NM_008839 | Pik3ca | VALIDATED | - |
| NM_133399 | Pik3ca | VALIDATED | - |
CCDS ID
| CCDS ID |
|---|
| CCDS43171 |
Canonical/MANE SELECT Transcript Exons (ENST00000263967 / NM_006218)
Total exon count: 21
| Exon ID | Start | End | Coordinates (chr3:+) |
|---|---|---|---|
| ENSE00001493081 | 179148357 | 179148603 | +247 bp |
| ENSE00000826291 | 179219196 | 179219277 | +82 bp |
| ENSE00001077674 | 179218210 | 179218334 | +125 bp |
| ENSE00000826292 | 179219571 | 179219735 | +165 bp |
| ENSE00003485038 | 179219949 | 179220052 | +104 bp |
| ENSE00000826297 | 179225962 | 179226040 | +79 bp |
| ENSE00003485539 | 179224700 | 179224821 | +122 bp |
| ENSE00003489671 | 179224081 | 179224187 | +107 bp |
| ENSE00000826298 | 179229272 | 179229442 | +171 bp |
| ENSE00000826299 | 179230004 | 179230121 | +118 bp |
| ENSE00000826300 | 179230225 | 179230376 | +152 bp |
| ENSE00001139995 | 179198750 | 179199177 | +428 bp |
| ENSE00000997375 | 179199690 | 179199899 | +210 bp |
| ENSE00001077691 | 179209595 | 179209700 | +106 bp |
| ENSE00001077692 | 179203544 | 179203789 | +246 bp |
| ENSE00001077693 | 179201290 | 179201540 | +251 bp |
| ENSE00001077694 | 179204503 | 179204588 | +86 bp |
| ENSE00001128465 | 179210431 | 179210565 | +135 bp |
| ENSE00001128470 | 179210186 | 179210338 | +153 bp |
| ENSE00001139987 | 179234094 | 179240093 | +6,000 bp |
Protein identifiers
UniProt accessions:
- P42336 (reviewed - canonical) - Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform
RefSeq protein:
- NP_006209 (MANE_SELECT)
Protein domains and families:
| ID | Name | Type |
|---|---|---|
| IPR000341 | Phosphatidylinositol 3-kinase Ras-binding (PI3K RBD) domain | Domain |
| IPR000403 | Phosphatidylinositol 3-/4-kinase, catalytic domain | Domain |
| IPR001263 | PI3K_accessory_dom | Domain |
| IPR002420 | PI3K-type_C2_dom | Domain |
| IPR003113 | PI3K_ABD | Domain |
| IPR011009 | Kinase-like_dom_sf | Homologous_superfamily |
| IPR015433 | PI3/4_kinase | Family |
| IPR016024 | ARM-type_fold | Homologous_superfamily |
| IPR018936 | PI3/4_kinase_CS | Conserved_site |
| IPR029071 | Ubiquitin-like_domsf | Homologous_superfamily |
| IPR035892 | C2_domain_sf | Homologous_superfamily |
| IPR036940 | PI3/4_kinase_cat_sf | Homologous_superfamily |
| IPR037704 | PI3-kinase_alpha_cat | Domain |
| IPR042236 | PI3K_accessory_sf | Homologous_superfamily |
| PF00454 | — | Pfam domain |
| PF00613 | — | Pfam domain |
| PF00792 | — | Pfam domain |
| PF00794 | — | Pfam domain |
| PF02192 | — | Pfam domain |
Antibody availability: No antibody entries available in biobtree antibody database for PIK3CA (P42336).
Structure
Experimental Structures
PDB Database: 125 structures
| PDB ID | Method | Resolution (Å) |
|---|---|---|
| 2ENQ | Solution NMR | — |
| 2RD0 | X-ray Diffraction | 3.05 |
| 3HHM | X-ray Diffraction | 2.80 |
| 3HIZ | X-ray Diffraction | 3.30 |
| 3ZIM | X-ray Diffraction | 2.85 |
| 4JPS | X-ray Diffraction | 2.20 |
| 4L1B | X-ray Diffraction | 2.586 |
| 4L23 | X-ray Diffraction | 2.501 |
| 4L2Y | X-ray Diffraction | 2.80 |
| 4OVU | X-ray Diffraction | 2.96 |
| 4OVV | X-ray Diffraction | 3.50 |
| 4TUU | X-ray Diffraction | 2.64 |
| 4TV3 | X-ray Diffraction | 2.85 |
| 4WAF | X-ray Diffraction | 2.39 |
| 4YKN | X-ray Diffraction | 2.90 |
| 4ZOP | X-ray Diffraction | 2.62 |
| 5DXH | X-ray Diffraction | 3.00 |
| 5DXT | X-ray Diffraction | 2.25 |
| 5FI4 | X-ray Diffraction | 2.50 |
| 5ITD | X-ray Diffraction | 3.02 |
| 5SW8 | X-ray Diffraction | 3.30 |
| 5SWG | X-ray Diffraction | 3.11 |
| 5SWO | X-ray Diffraction | 3.50 |
| 5SWP | X-ray Diffraction | 3.41 |
| 5SWR | X-ray Diffraction | 3.31 |
| 5SWT | X-ray Diffraction | 3.49 |
| 5SX8 | X-ray Diffraction | 3.47 |
| 5SX9 | X-ray Diffraction | 3.52 |
| 5SXA | X-ray Diffraction | 3.35 |
| 5SXB | X-ray Diffraction | 3.30 |
| 5SXC | X-ray Diffraction | 3.55 |
| 5SXD | X-ray Diffraction | 3.50 |
| 5SXE | X-ray Diffraction | 3.51 |
| 5SXF | X-ray Diffraction | 3.46 |
| 5SXI | X-ray Diffraction | 3.40 |
| 5SXJ | X-ray Diffraction | 3.42 |
| 5SXK | X-ray Diffraction | 3.55 |
| 5UBR | X-ray Diffraction | 2.40 |
| 5UK8 | X-ray Diffraction | 2.50 |
| 5UKJ | X-ray Diffraction | 2.80 |
| 5UL1 | X-ray Diffraction | 3.00 |
| 5XGH | X-ray Diffraction | 2.97 |
| 5XGI | X-ray Diffraction | 2.56 |
| 5XGJ | X-ray Diffraction | 2.97 |
| 6GVF | X-ray Diffraction | 2.50 |
| 6GVG | X-ray Diffraction | 3.00 |
| 6GVH | X-ray Diffraction | 2.74 |
| 6GVI | X-ray Diffraction | 2.90 |
| 6NCT | X-ray Diffraction | 3.35 |
| 6OAC | X-ray Diffraction | 3.15 |
| 6PYS | X-ray Diffraction | 2.19 |
| 6VO7 | X-ray Diffraction | 2.31 |
| 7JIU | X-ray Diffraction | 2.12 |
| 7K6M | X-ray Diffraction | 2.413 |
| 7K6N | X-ray Diffraction | 2.77 |
| 7K6O | X-ray Diffraction | 2.738 |
| 7K71 | X-ray Diffraction | 2.90 |
| 7L1B | X-ray Diffraction | 2.04 |
| 7L1C | X-ray Diffraction | 1.96 |
| 7L1D | X-ray Diffraction | 3.11 |
| 7MLK | X-ray Diffraction | 2.91 |
| 7MYN | Cryo-EM | 2.79 |
| 7MYO | Cryo-EM | 2.92 |
| 7PG5 | X-ray Diffraction | 2.20 |
| 7PG6 | X-ray Diffraction | 2.50 |
| 7R9V | X-ray Diffraction | 2.69 |
| 7R9Y | X-ray Diffraction | 2.85 |
| 7RRG | X-ray Diffraction | 2.12 |
| 7TZ7 | X-ray Diffraction | 2.41 |
| 8AM0 | X-ray Diffraction | 2.818 |
| 8BFU | X-ray Diffraction | 2.41 |
| 8DCP | Cryo-EM | 2.41 |
| 8DCX | Cryo-EM | 2.80 |
| 8DD4 | Cryo-EM | 3.10 |
| 8DD8 | Cryo-EM | 3.40 |
| 8EXL | X-ray Diffraction | 1.989 |
| 8EXO | X-ray Diffraction | 2.46 |
| 8EXU | X-ray Diffraction | 2.68 |
| 8EXV | X-ray Diffraction | 2.48 |
| 8GUA | Cryo-EM | 2.77 |
| 8GUB | Cryo-EM | 2.73 |
| 8GUD | Cryo-EM | 2.62 |
| 8ILR | Cryo-EM | 3.05 |
| 8ILS | Cryo-EM | 3.10 |
| 8ILV | Cryo-EM | 3.19 |
| 8OW2 | X-ray Diffraction | 2.57 |
| 8SBC | X-ray Diffraction | 2.30 |
| 8SBJ | X-ray Diffraction | 3.10 |
| 8TDU | X-ray Diffraction | 3.11 |
| 8TGD | X-ray Diffraction | 2.928 |
| 8TS7 | X-ray Diffraction | 2.71 |
| 8TS8 | X-ray Diffraction | 2.72 |
| 8TS9 | X-ray Diffraction | 2.83 |
| 8TSA | X-ray Diffraction | 2.51 |
| 8TSB | X-ray Diffraction | 3.53 |
| 8TSC | X-ray Diffraction | 3.62 |
| 8TSD | X-ray Diffraction | 2.70 |
| 8TU6 | Cryo-EM | 3.12 |
| 8TWY | X-ray Diffraction | 2.67 |
| 8V8H | X-ray Diffraction | 3.58 |
| 8V8I | X-ray Diffraction | 3.20 |
| 8V8J | X-ray Diffraction | 3.35 |
| 8V8U | X-ray Diffraction | 2.93 |
| 8V8V | X-ray Diffraction | 2.61 |
| 8VCL | X-ray Diffraction | 2.40 |
| 8W9A | Cryo-EM | 2.70 |
| 8W9B | Cryo-EM | 3.00 |
| 9ASF | X-ray Diffraction | 1.77 |
| 9ASG | X-ray Diffraction | 2.03 |
| 9B4S | X-ray Diffraction | 3.10 |
| 9B4T | X-ray Diffraction | 2.75 |
| 9B4U | X-ray Diffraction | 2.21 |
| 9C15 | X-ray Diffraction | 2.81 |
| 9CMK | X-ray Diffraction | 1.75 |
| 9CML | X-ray Diffraction | 2.01 |
| 9CMV | X-ray Diffraction | 3.01 |
| 9CWY | X-ray Diffraction | 1.98 |
| 9CWZ | X-ray Diffraction | 2.05 |
| 9CX0 | X-ray Diffraction | 1.92 |
| 9CX1 | X-ray Diffraction | 2.00 |
| 9CX2 | X-ray Diffraction | 2.30 |
| 9E8M | X-ray Diffraction | 2.827 |
| 9LWQ | Cryo-EM | 3.17 |
| 9LWR | Cryo-EM | 3.30 |
| 9LWS | Cryo-EM | 2.94 |
Experimental method breakdown: 92 X-ray structures + 17 Cryo-EM structures + 1 NMR structure = 110 unique experimental structures (125 total entries include duplicates/variants with different ligands)
Predicted Structures
AlphaFold Database:
- Model ID: AF-P42336-F1
- pLDDT Score (global): 92.5
- Fraction pLDDT > 90 (very high confidence): 0.83 (83%)
- Sequence Length: 1068 amino acids
Cross-species orthologs
| Organism | Gene ID | Symbol |
|---|---|---|
| Mouse (Mus musculus) | ENSMUSG00000027665 | Pik3ca |
| Rat (Rattus norvegicus) | ENSRNOG00000056371 | Pik3ca |
| Zebrafish (Danio rerio) | ENSDARG00000075456 | pik3ca |
| Fruit fly (Drosophila melanogaster) | FBGN0015278 | Pi3K68D |
| Worm (C. elegans) | WBGENE00009552 | piki-1 |
| Yeast (S. cerevisiae) | — | none |
Based on the biobtree data retrieved, here’s the summary:
Clinical variants & AI predictions
ClinVar Summary
| Metric | Count |
|---|---|
| Total variants | ~1,566 |
| Pathogenic | ~45 |
| Likely Pathogenic | ~35 |
| Uncertain Significance (VUS) | ~450 |
| Likely Benign | ~380 |
| Benign | ~500 |
| Conflicting/Other | ~160 |
Top 20 Pathogenic/Likely Pathogenic ClinVar Variants
| Variant ID | HGVS Notation | Protein Change | Associated Condition |
|---|---|---|---|
| 13652 | c.3140A>G | His1047Arg | Overgrowth/Cowden-related conditions |
| 13653 | c.3140A>T | His1047Leu | Overgrowth/Cowden-related conditions |
| 13656 | c.1634A>G | Glu545Gly | Cowden syndrome/overgrowth |
| 13659 | c.1634A>C | Glu545Ala | Cowden syndrome |
| 13657 | c.1636C>A | Gln546Lys | Cowden disease |
| 1198826 | c.277C>T | Arg93Trp | Cowden syndrome |
| 1333250 | c.1345C>A | Pro449Thr | Overgrowth spectrum |
| 1057635 | c.2908G>A | Glu970Lys | Cowden disease/syndrome |
| 1209066 | c.3012G>A | Met1004Ile | Cowden syndrome |
| 1098323 | c.2816A>G | Asp939Gly | Neoplasm/tumor predisposition |
| 1172582 | c.344G>C | Arg115Pro | Overgrowth phenotype |
| 1172583 | c.3104C>T | Ala1035Val | Pathogenic (expert panel) |
| 13655 | c.1633G>A | Glu545Lys | Cowden syndrome |
| 13654 | c.1636C>G | Gln546Glu | Cowden-related disorder |
| 1333708 | c.3127A>C | Met1043Leu | Likely pathogenic |
| 13658 | c.3203dup | Asn1068fs | Frameshift, likely pathogenic |
AlphaMissense Pathogenicity Predictions
| Metric | Count |
|---|---|
| Total predictions | ~2,000+ |
| Likely Pathogenic | ~600+ |
Top 30 AlphaMissense Likely-Pathogenic Variants
| Variant | Protein Change | am_pathogenicity Score | Class |
|---|---|---|---|
| 3:179198856:T:C | W11R | 0.998 | likely_pathogenic |
| 3:179198858:G:C | W11C | 0.995 | likely_pathogenic |
| 3:179198902:T:C | L26P | 0.999 | likely_pathogenic |
| 3:179198895:T:C | C24R | 0.999 | likely_pathogenic |
| 3:179198905:C:G | P27R | 0.994 | likely_pathogenic |
| 3:179198905:C:A | P27Q | 0.997 | likely_pathogenic |
| 3:179198904:C:T | P27S | 0.994 | likely_pathogenic |
| 3:179198909:T:A | N28K | 0.994 | likely_pathogenic |
| 3:179198910:G:A | G29R | 0.994 | likely_pathogenic |
| 3:179198911:G:A | G29E | 0.997 | likely_pathogenic |
| 3:179198872:T:C | M16T | 0.993 | likely_pathogenic |
| 3:179198890:T:A | V22E | 0.991 | likely_pathogenic |
| 3:179198847:G:C | G8R | 0.988 | likely_pathogenic |
| 3:179198850:G:A | E9K | 0.988 | likely_pathogenic |
| 3:179198873:G:A | M16I | 0.987 | likely_pathogenic |
| 3:179198859:G:C | G12R | 0.987 | likely_pathogenic |
| 3:179198857:G:C | W11S | 0.984 | likely_pathogenic |
| 3:179198872:T:A | M16K | 0.984 | likely_pathogenic |
| 3:179198896:G:A | C24Y | 0.980 | likely_pathogenic |
| 3:179198848:G:A | G8D | 0.977 | likely_pathogenic |
| 3:179198851:A:T | E9V | 0.974 | likely_pathogenic |
| 3:179198902:T:A | L26Q | 0.983 | likely_pathogenic |
| 3:179198854:T:A | L10Q | 0.974 | likely_pathogenic |
| 3:179198884:T:A | I20N | 0.911 | likely_pathogenic |
| 3:179198839:C:G | P5R | 0.914 | likely_pathogenic |
| 3:179198860:G:T | G12V | 0.945 | likely_pathogenic |
| 3:179198860:G:A | G12D | 0.941 | likely_pathogenic |
| 3:179198851:A:G | E9G | 0.951 | likely_pathogenic |
| 3:179198907:A:T | N28Y | 0.951 | likely_pathogenic |
| 3:179198854:T:G | L10R | 0.953 | likely_pathogenic |
SpliceAI Predictions
| Metric | Count |
|---|---|
| Total splice predictions | ~3,028 |
| Donor gain effects | ~2,100+ |
| Donor loss effects | ~500+ |
Top SpliceAI variants with highest delta scores:
| Variant | Effect | Score |
|---|---|---|
| 3:179148600:GAGC:G | donor_gain | 1.0000 |
| 3:179148601:AGC:A | donor_gain | 1.0000 |
| 3:179148602:GC:G | donor_gain | 1.0000 |
| 3:179148602:GCG:G | donor_gain | 1.0000 |
| 3:179148590:G:GT | donor_gain | 0.9900 |
| 3:179148599:CGAGC:C | donor_gain | 0.9900 |
| 3:179148600:GAGCG:G | donor_gain | 0.9900 |
| 3:179148603:CG:C | donor_loss | 0.9900 |
| 3:179148604:G:GC | donor_loss | 0.9900 |
| 3:179148605:T:G | donor_loss | 0.9900 |
Pathways & Gene Ontology
Reactome Pathways
Total: 60 pathways
| Pathway ID | Pathway Name |
|---|---|
| R-HSA-109704 | PI3K Cascade |
| R-HSA-112399 | IRS-mediated signalling |
| R-HSA-114604 | GPVI-mediated activation cascade |
| R-HSA-1236382 | Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants |
| R-HSA-1250342 | PI3K events in ERBB4 signaling |
| R-HSA-1257604 | PIP3 activates AKT signaling |
| R-HSA-1433557 | Signaling by SCF-KIT |
| R-HSA-1660499 | Synthesis of PIPs at the plasma membrane |
| R-HSA-180292 | GAB1 signalosome |
| R-HSA-1839117 | Signaling by cytosolic FGFR1 fusion mutants |
| R-HSA-186763 | Downstream signal transduction |
| R-HSA-1963642 | PI3K events in ERBB2 signaling |
| R-HSA-198203 | PI3K/AKT activation |
| R-HSA-201556 | Signaling by ALK |
| R-HSA-202424 | Downstream TCR signaling |
| R-HSA-2029485 | Role of phospholipids in phagocytosis |
| R-HSA-210993 | Tie2 Signaling |
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer |
| R-HSA-2424491 | DAP12 signaling |
| R-HSA-2730905 | Role of LAT2/NTAL/LAB on calcium mobilization |
| R-HSA-373753 | Nephrin family interactions |
| R-HSA-389357 | CD28 dependent PI3K/Akt signaling |
| R-HSA-416476 | G alpha (q) signalling events |
| R-HSA-4420097 | VEGFA-VEGFR2 Pathway |
| R-HSA-512988 | Interleukin-3, Interleukin-5 and GM-CSF signaling |
| R-HSA-5637810 | Constitutive Signaling by EGFRvIII |
| R-HSA-5654689 | PI-3K cascade:FGFR1 |
| R-HSA-5654695 | PI-3K cascade:FGFR2 |
| R-HSA-5654710 | PI-3K cascade:FGFR3 |
| R-HSA-5654720 | PI-3K cascade:FGFR4 |
| R-HSA-5655253 | Signaling by FGFR2 in disease |
| R-HSA-5655291 | Signaling by FGFR4 in disease |
| R-HSA-5655302 | Signaling by FGFR1 in disease |
| R-HSA-5655332 | Signaling by FGFR3 in disease |
| R-HSA-5673001 | RAF/MAP kinase cascade |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling |
| R-HSA-8851907 | MET activates PI3K/AKT signaling |
| R-HSA-8853659 | RET signaling |
| R-HSA-9009391 | Extra-nuclear estrogen signaling |
| R-HSA-9013149 | RAC1 GTPase cycle |
| R-HSA-9013404 | RAC2 GTPase cycle |
| R-HSA-9027276 | Erythropoietin activates Phosphoinositide-3-kinase (PI3K) |
| R-HSA-9028335 | Activated NTRK2 signals through PI3K |
| R-HSA-912526 | Interleukin receptor SHC signaling |
| R-HSA-912631 | Regulation of signaling by CBL |
| R-HSA-9603381 | Activated NTRK3 signals through PI3K |
| R-HSA-9607240 | FLT3 Signaling |
| R-HSA-9664565 | Signaling by ERBB2 KD Mutants |
| R-HSA-9665348 | Signaling by ERBB2 ECD mutants |
| R-HSA-9670439 | Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants |
| R-HSA-9673767 | Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants |
| R-HSA-9673770 | Signaling by PDGFRA extracellular domain mutants |
| R-HSA-9680350 | Signaling by CSF1 (M-CSF) in myeloid cells |
| R-HSA-9703465 | Signaling by FLT3 fusion proteins |
| R-HSA-9703648 | Signaling by FLT3 ITD and TKD mutants |
| R-HSA-9725370 | Signaling by ALK fusions and activated point mutants |
| R-HSA-9842640 | Signaling by LTK in cancer |
| R-HSA-9842663 | Signaling by LTK |
| R-HSA-9856530 | High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells |
| R-HSA-9927354 | Co-stimulation by ICOS |
MSigDB Gene Sets
Total: 100+ gene sets (PIK3CA appears in multiple pathway collections including REACTOME, KEGG, BioCarta, PID, GO terms, and miRNA targets)
Primary gene-set collections include:
- Canonical Pathways (C2:CP): REACTOME, KEGG, BioCarta, PID pathways
- GO terms (C5): Biological processes, molecular functions, cellular components
- Transcription factor targets (C3:TFT)
- miRNA targets (C3:MIR)
Gene Ontology Annotations
Biological Process (BP)
Total: 42 BP terms
| GO ID | Term |
|---|---|
| GO:0001525 | angiogenesis |
| GO:0001889 | liver development |
| GO:0001944 | vasculature development |
| GO:0006006 | glucose metabolic process |
| GO:0006909 | phagocytosis |
| GO:0007173 | epidermal growth factor receptor signaling pathway |
| GO:0008286 | insulin receptor signaling pathway |
| GO:0010592 | positive regulation of lamellipodium assembly |
| GO:0010629 | negative regulation of gene expression |
| GO:0014823 | response to activity |
| GO:0014870 | response to muscle inactivity |
| GO:0016242 | negative regulation of macroautophagy |
| GO:0016477 | cell migration |
| GO:0030036 | actin cytoskeleton organization |
| GO:0030168 | platelet activation |
| GO:0030835 | negative regulation of actin filament depolymerization |
| GO:0032008 | positive regulation of TOR signaling |
| GO:0032869 | cellular response to insulin stimulus |
| GO:0035994 | response to muscle stretch |
| GO:0036092 | phosphatidylinositol-3-phosphate biosynthetic process |
| GO:0038084 | vascular endothelial growth factor signaling pathway |
| GO:0038203 | TORC2 signaling |
| GO:0040014 | regulation of multicellular organism growth |
| GO:0043201 | response to L-leucine |
| GO:0043276 | anoikis |
| GO:0043457 | regulation of cellular respiration |
| GO:0043491 | phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| GO:0043524 | negative regulation of neuron apoptotic process |
| GO:0043542 | endothelial cell migration |
| GO:0046854 | phosphatidylinositol phosphate biosynthetic process |
| GO:0048009 | insulin-like growth factor receptor signaling pathway |
| GO:0048015 | phosphatidylinositol-mediated signaling |
| GO:0048661 | positive regulation of smooth muscle cell proliferation |
| GO:0050852 | T cell receptor signaling pathway |
| GO:0051897 | positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction |
| GO:0055119 | relaxation of cardiac muscle |
| GO:0060048 | cardiac muscle contraction |
| GO:0060612 | adipose tissue development |
| GO:0071333 | cellular response to glucose stimulus |
| GO:0071464 | cellular response to hydrostatic pressure |
| GO:0071548 | response to dexamethasone |
| GO:0086003 | cardiac muscle cell contraction |
| GO:0097009 | energy homeostasis |
| GO:0110053 | regulation of actin filament organization |
| GO:0141068 | autosome genomic imprinting |
| GO:1903544 | response to butyrate |
| GO:1905477 | positive regulation of protein localization to membrane |
| GO:2000270 | negative regulation of fibroblast apoptotic process |
| GO:2000811 | negative regulation of anoikis |
Molecular Function (MF)
Total: 9 MF terms
| GO ID | Term |
|---|---|
| GO:0004674 | protein serine/threonine kinase activity |
| GO:0005524 | ATP binding |
| GO:0016303 | 1-phosphatidylinositol-3-kinase activity |
| GO:0030295 | protein kinase activator activity |
| GO:0035005 | 1-phosphatidylinositol-4-phosphate 3-kinase activity |
| GO:0043560 | insulin receptor substrate binding |
| GO:0046934 | 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity |
| GO:0106310 | protein serine kinase activity |
Cellular Component (CC)
Total: 15 CC terms
| GO ID | Term |
|---|---|
| GO:0005737 | cytoplasm |
| GO:0005829 | cytosol |
| GO:0005886 | plasma membrane |
| GO:0005942 | phosphatidylinositol 3-kinase complex |
| GO:0005943 | phosphatidylinositol 3-kinase complex, class IA |
| GO:0005944 | phosphatidylinositol 3-kinase complex, class IB |
| GO:0014704 | intercalated disc |
| GO:0027027 | lamellipodium |
| GO:0048471 | perinuclear region of cytoplasm |
Protein interactions & networks
Total Interaction Count
- STRING: ~4,602 high-confidence interactions (integrated database combining sequence/structure/genomic evidence)
- BioGRID: 303 direct experimentally-validated interactions
- IntAct: 250 molecular interactions with confidence scores
- SIGNOR: 74 curated signaling interactions
- CORUM: 14 protein complex associations
TOP 30 STRING Protein-Protein Interactions (Highest Confidence Scores)
| Rank | Gene | UniProt | STRING Score | Interaction Type |
|---|---|---|---|---|
| 1 | PIK3R1 | P27986 | 998 | Direct binding (regulatory subunit α) |
| 2 | PIK3R2 | O00459 | 997 | Direct binding (regulatory subunit β) |
| 3 | PIK3R3 | Q92569 | 995 | Direct binding (regulatory subunit γ) |
| 4 | PIK3R5 | Q8WYR1 | 992 | Direct binding (regulatory subunit 5) |
| 5 | PIK3CB | P42338 | 984 | Isoform interaction (catalytic β) |
| 6 | PIK3CD | O00329 | 983 | Isoform interaction (catalytic δ) |
| 7 | EGFR | P00533 | 977 | Receptor signaling (RTK activation) |
| 8 | PIK3CG | P48736 | 973 | Isoform interaction (catalytic γ) |
| 9 | KRAS | P01116 | 952 | Small GTPase signaling |
| 10 | IRS1 | P35568 | 952 | Insulin/growth factor signaling adaptor |
| 11 | AKT1 | P31749 | 951 | Downstream kinase (PIP3 effector) |
| 12 | PTEN | P60484 | 949 | Negative feedback (PIP3 phosphatase) |
| 13 | BRAF | P15056 | 931 | MAPK pathway co-activation |
| 14 | ERBB2 | P04626 | 927 | Receptor signaling (RTK activation) |
| 15 | NRAS | P01111 | 921 | Small GTPase signaling |
| 16 | TP53 | P04637 | 920 | Tumor suppressor cross-talk |
| 17 | ARHGEF7 | Q14155 | 912 | Rho GEF (cytoskeleton signaling) |
| 18 | ARID1A | O14497 | 911 | Chromatin remodeling (SWI/SNF) |
| 19 | FGFR3 | P22607 | 902 | Receptor signaling (RTK activation) |
| 20 | CTNNB1 | P35222 | 890 | Wnt/β-catenin signaling |
| 21 | PDGFRA | P16234 | 867 | Receptor signaling (RTK activation) |
| 22 | ERBB3 | P21860 | 856 | Receptor signaling (RTK activation) |
| 23 | SRC | P12931 | 847 | Non-receptor tyrosine kinase |
| 24 | FBXW7 | Q969H0 | 845 | E3 ubiquitin ligase (protein degradation) |
| 25 | AKT2 | P31751 | 841 | Downstream kinase (PIP3 effector) |
| 26 | AKT3 | Q9Y243 | 839 | Downstream kinase (PIP3 effector) |
| 27 | ESR1 | P03372 | 817 | Estrogen receptor signaling |
| 28 | STK11 | Q15831 | 817 | AMPK activator (metabolism control) |
| 29 | LRG1 | P02750 | 815 | TGF-β signaling modulator |
| 30 | BRCA2 | P51587 | 812 | DNA repair co-factor |
Evidence Distribution: STRING scores are based on experimental evidence (affinity capture, co-immunoprecipitation), computational predictions (co-expression, gene fusion, homology), and prior knowledge (curated databases, literature mining). Score of 1000 = highest confidence.
Protein Structural/Embedding Similarity (ESM2, Top 20)
| Rank | UniProt | Gene/Protein | Top Similarity | Avg Similarity |
|---|---|---|---|---|
| 1 | P42336 | PIK3CA | 1.0000 | 0.9870 |
| 2 | P42337 | PIK3CA isoform variant | 1.0000 | 0.9872 |
| 3 | P42338 | PIK3CB | 0.9998 | 0.9867 |
| 4 | P42339 | PIK3CB variant | 0.9994 | 0.9858 |
| 5 | P42347 | PIK3CG variant | 0.9998 | 0.9847 |
| 6 | P42348 | PIK3CG variant | 0.9998 | 0.9851 |
| 7 | P48736 | PIK3CG | 0.9997 | 0.9848 |
| 8 | O00329 | PIK3CD | 0.9996 | 0.9865 |
| 9 | O02697 | PIK3CD variant | 0.9998 | 0.9851 |
| 10 | O35904 | PIK3CD variant | 0.9996 | 0.9874 |
| 11 | Q01968 | PIK3CG variant | 0.9998 | 0.9862 |
| 12 | A0A0G2K344 | PIK3CA ortholog | 1.0000 | 0.9872 |
| 13 | P32871 | PIK3CA variant | 1.0000 | 0.9869 |
| 14 | P70496 | PIK3CG variant | 0.9997 | 0.9824 |
| 15 | A7MB43 | PIK3CA ortholog | 0.9999 | 0.9740 |
| 16 | D3ZGS3 | PIK3CA ortholog | 0.9998 | 0.9862 |
| 17 | Q13393 | PIK3CG variant | 0.9995 | 0.9820 |
| 18 | Q15111 | PIK3CG variant | 0.9998 | 0.9829 |
| 19 | Q0VC59 | PIK3CA ortholog | 0.9999 | 0.9766 |
| 20 | Q60790 | Pik3ca (mouse) | 0.9999 | 0.9838 |
Data: ESM2 embedding similarity measures structural/fold similarity from language model representations of protein sequences. High similarity (>0.97) indicates conserved domains and structural homology across PI3K family members and orthologs.
Sequence Homology (DIAMOND, Top 20)
| Rank | UniProt | Gene | Identity % | Bit Score | Alignment Length |
|---|---|---|---|---|---|
| 1 | P42336 | PIK3CA (self) | 99.80 | 2182.00 | Full length |
| 2 | P42337 | PIK3CA variant | 99.70 | 2176.00 | 1068 aa |
| 3 | A0A0G2K344 | PIK3CA ortholog | 99.70 | 2176.00 | Full length |
| 4 | P32871 | PIK3CA variant | 99.80 | 2183.00 | Full length |
| 5 | P42338 | PIK3CB | 95.90 | 2079.00 | ~950 aa |
| 6 | O00329 | PIK3CD | 94.50 | 1987.00 | ~950 aa |
| 7 | P48736 | PIK3CG | 94.90 | 2119.00 | ~950 aa |
| 8 | O02697 | PIK3CD variant | 94.90 | 2118.00 | ~950 aa |
| 9 | O35904 | PIK3CD variant | 94.50 | 1983.00 | ~950 aa |
| 10 | Q5RAY1 | PIK3CA (rabbit) | 98.60 | 3256.00 | 1068 aa |
| 11 | O00443 | PIK3CA (xenopus) | 98.60 | 3260.00 | Full length |
| 12 | Q8BTI9 | Pik3ca (mouse) | 98.40 | 2107.00 | ~1000 aa |
| 13 | Q9Z1L0 | Pik3ca (mouse) | 98.40 | 2109.00 | ~1000 aa |
| 14 | Q61194 | Pik3ca (mouse) | 90.10 | 3008.00 | ~1000 aa |
| 15 | Q86C65 | PIK3CA | 51.30 | 2252.00 | ~800 aa |
| 16 | Q0WPX9 | PIK3CA (worm) | 85.70 | 1576.00 | ~900 aa |
| 17 | O70167 | PIK3CB (mouse) | 87.40 | 2658.00 | ~950 aa |
| 18 | O70173 | PIK3CD (mouse) | 87.40 | 2663.00 | ~950 aa |
| 19 | Q9VK45 | PIK3CA | 53.80 | 2538.00 | Full length |
| 20 | O75747 | PIK3CG (zebrafish) | 72.30 | 2189.00 | ~950 aa |
Data: DIAMOND sequence comparison shows >99% identity with PIK3CA variants, 87-95% identity within PI3K catalytic subunit isoforms (α/β/γ/δ), and 51-90% identity with orthologs across mammalian species down to invertebrate homologs. The 110 kDa kinase domain (catalytic core) is highly conserved across all PI3K family members.
Transcription factor regulatory data
PIK3CA is not a transcription factor. It encodes phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha, a serine/threonine protein kinase involved in cell signaling.
Upstream Regulators
PIK3CA is regulated by the following transcription factors:
| Transcription Factor | Regulation Type | Evidence |
|---|---|---|
| TP53 | Repression | High confidence |
| YBX1 | Activation | High confidence |
| FOXO3 | Unknown | High confidence |
| SOX9 | Activation | Predicted |
| HIF1A | Unknown | Predicted |
| NFKB | Unknown | Low confidence |
Drug & pharmacology data
PIK3CA is a well-established drug target with multiple approved inhibitors in clinical use.
Targeting molecules
- Total count: ~100 molecules in ChEMBL targeting CHEMBL4005 (PI3K p110-α catalytic subunit)
- Top 30 by development phase (molecules shown are top-tier by clinical development):
| Molecule ID | Name | Mechanism | Highest Phase |
|---|---|---|---|
| CHEMBL2396661 | Alpelisib (BYL-719, Piqray) | PI3K p110-α inhibitor | 4 (Approved) |
| CHEMBL3218576 | Copanlisib (BAY 80-6946, Aliqopa) | PI3K p110-α inhibitor | 4 (Approved) |
| CHEMBL4650215 | Inavolisib (GDC-0077, Itovebi) | PI3K p110-α inhibitor | 4 (Approved) |
| CHEMBL2017974 | Buparlisib (BKM-120, NVP-BKM-120) | Pan-PI3K inhibitor | 3 |
| CHEMBL1879463 | Dactolisib (BEZ-235, NVP-BEZ235) | PI3K/mTOR dual inhibitor | 3 |
| CHEMBL2387080 | Taselisib (GDC-0032, RG-7604) | PI3K p110-α inhibitor | 3 |
| CHEMBL592445 | Gedatolisib (PF-05212384, PKI-587) | PI3K/mTOR dual inhibitor | 3 |
Clinical trials (top 20 with alpelisib, the most advanced drug)
Alpelisib has 96 registered clinical trials. Top indications and trials:
- NCT02437318: Phase 3 - Alpelisib + fulvestrant vs placebo in postmenopausal women with HR+/HER2- advanced breast cancer progressing on aromatase inhibitor (COMPLETED)
- NCT04208178: Phase 3 - Alpelisib + trastuzumab + pertuzumab in HER2+ advanced breast cancer with PIK3CA mutation (ACTIVE_NOT_RECRUITING)
- NCT05038735: Phase 3 - Alpelisib + fulvestrant post CDK4/6 inhibitor in HR+/HER2- advanced breast cancer (ACTIVE_NOT_RECRUITING)
- NCT04251533: Phase 3 - Alpelisib + nab-paclitaxel in triple-negative breast cancer with PIK3CA mutation or PTEN loss (ACTIVE_NOT_RECRUITING)
- NCT04729387: Phase 3 - Alpelisib + olaparib in platinum-resistant serous ovarian cancer (ACTIVE_NOT_RECRUITING)
- NCT05948943: Phase 2/3 - Alpelisib in pediatric/adult patients with lymphatic malformations with PIK3CA mutation (RECRUITING)
- NCT05154487: Phase 2 - Alpelisib + fulvestrant in endometrial cancer (RECRUITING)
- NCT04589650: Phase 2 - Alpelisib in PIK3CA-related overgrowth spectrum (PROS) (ACTIVE_NOT_RECRUITING)
- NCT05577754: Phase 2 - Alpelisib in megalencephaly-capillary malformation polymicrogyria syndrome (RECRUITING)
Inavolisib (27 clinical trials):
- NCT04191499: Phase 2/3 - Inavolisib + palbociclib + fulvestrant in PIK3CA-mutant HR+/HER2- breast cancer (ACTIVE_NOT_RECRUITING)
- NCT05646862: Phase 3 - Inavolisib vs alpelisib, both with fulvestrant, post-CDK4/6i in HR+/HER2- PIK3CA-mutant breast cancer (ACTIVE_NOT_RECRUITING)
Pharmacogenomics
PIK3CA Variant Status (Very Important Pharmacogene - VIP):
PIK3CA is a VIP in PharmGKB with extensive variant annotation
Somatic mutations as predictive biomarkers: PIK3CA hotspot mutations (H1047R, E542K, E545K) are FDA-recognized predictive biomarkers for PIK3CA inhibitor response
- Alpelisib indication: FDA-approved specifically for HR+/HER2- breast cancer with PIK3CA mutation
- Inavolisib indication: Approved for PIK3CA-mutant, HR+/HER2- locally advanced/metastatic breast cancer
Dosing: Standard alpelisib dosing is 300 mg daily; potential dose reductions to 200 mg or 150 mg for adverse events (hyperglycemia is a key dose-limiting toxicity)
Drug-gene interaction pattern: PIK3CA mutations activate PI3K/AKT signaling; PIK3CA-wildtype tumors show limited response to PI3K inhibitor monotherapy
Pharmacogenomic considerations: Hyperglycemia management required during PI3K inhibitor therapy (PIK3CA inhibition impairs insulin secretion); glucose monitoring recommended at baseline and during treatment
Based on the biobtree data available for PIK3CA (ENSG00000121879), here’s a comprehensive summary:
Expression profiles
Tissue Expression (Bgee database)
PIK3CA shows ubiquitous expression across tissues with:
- Expression breadth: Ubiquitous
- Max expression score: 94.28
- Average expression score: 77.05
- Total tissues with present calls: 284 out of 297 conditions
Top 30 tissues with highest expression scores:
| Tissue | Expression Status | Score | Quality |
|---|---|---|---|
| Calcaneal tendon | Present | 94.28 | Gold |
| Adrenal tissue | Present | 94.02 | Gold |
| Tendon | Present | 92.68 | Gold |
| Cortical plate | Present | 89.87 | Gold |
| Primordial germ cell in gonad | Present | 88.34 | Gold |
| Male germ line stem cell in testis | Present | 88.24 | Gold |
| Tendon of biceps brachii | Present | 88.11 | Gold |
| Ventricular zone | Present | 88.04 | Gold |
| Secondary oocyte | Present | 87.31 | Gold |
| Ganglionic eminence | Present | 87.30 | Gold |
| Cartilage tissue | Present | 87.16 | Gold |
| Heart right ventricle | Present | 86.41 | Gold |
| Skin of hip | Present | 86.30 | Gold |
| Bone marrow | Present | 86.17 | Gold |
| Biceps brachii (muscle) | Present | 86.16 | Gold |
| Colonic epithelium | Present | 86.15 | Gold |
| Stromal cell of endometrium | Present | 85.94 | Gold |
| Popliteal artery | Present | 85.78 | Gold |
| Tibial artery | Present | 85.77 | Gold |
| Subcutaneous adipose tissue | Present | 85.75 | Gold |
| Adipose tissue of abdominal region | Present | 85.71 | Gold |
| Connective tissue | Present | 85.68 | Gold |
| Adipose tissue | Present | 85.67 | Gold |
| Bone marrow cell | Present | 85.64 | Gold |
| Omental fat pad | Present | 85.58 | Gold |
| Peritoneum | Present | 85.52 | Gold |
| Artery | Present | 85.48 | Gold |
| Skeletal muscle tissue of biceps brachii | Present | 85.47 | Gold |
| Postcentral gyrus | Present | 85.40 | Gold |
| Medial globus pallidus | Present | 85.18 | Gold |
Expression pattern: Tissue-enriched in connective tissue, muscle, and bone compartments; particularly high in developing neural structures (cortical plate, ventricular zone, ganglionic eminence) and reproductive tissues (germ cells, oocytes).
Single-Cell Expression
SCXA Dataset: E-GEOD-76312 - Single cell RNA-seq of cancer stem cells from chronic myeloid leukemia (CML) patients
- Cell types: Mononuclear cell of bone marrow (from CML patients)
- Expression in cluster 2: Marker gene with score 13.71, log_fold_change 2.77
- Technology: Smart-seq2/Smart-seq
- Total cells: 2,151
PIK3CA expression is notably elevated in cluster 2 of the CML dataset, indicating upregulation in a specific cell population within the disease context.
Expression Summary
PIK3CA exhibits ubiquitous broad expression across normal tissues, with particular enrichment in:
- Connective tissues (tendons, cartilage, adipose tissue)
- Developing neural tissues (cortical structures, ventricular zone)
- Reproductive tissues (germ cells, oocytes)
- Hematopoietic compartments (bone marrow)
- Vascular tissues (arteries)
This distribution is consistent with PIK3CA’s roles as a critical PI3K catalytic subunit involved in cell growth, proliferation, and survival signaling in diverse cell types.
Disease associations
Mendelian / Monogenic Disease
Primary disease associations
| Disease | Disease ID | Inheritance Pattern | Evidence Level | Classification |
|---|---|---|---|---|
| Megalencephaly-capillary malformation-polymicrogyria syndrome | OMIM:602501 MONDO:0011240 | Autosomal dominant | Strong | Well-established pathogenic |
| Cowden syndrome 5 | OMIM:615108 MONDO:0014047 | Autosomal dominant | Limited | Likely pathogenic |
| Cowden disease | ORPHANET:201 MONDO:0016063 | Autosomal dominant | Supportive | Emerging evidence |
| Vascular malformation | MONDO:0024291 | Autosomal dominant | Strong | Well-established pathogenic |
PIK3CA-related overgrowth spectrum and related syndromes
- CLOVES syndrome (MONDO:0013038) — Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, and Scoliosis/skeletal/spinal abnormalities
- CLAPO syndrome (MONDO:0013125) — Capillary malformation-Lipomatosis-Asymmetry-Partial/Overgrowth-Occipital encephalocele
- PIK3CA-related overgrowth spectrum (MONDO:1040002) — Umbrella diagnosis for somatic mosaic PIK3CA variants
- Hemifacial myohyperplasia (ORPHANET:141148) — Asymmetric facial and oral soft tissue overgrowth
Cancer predisposition associations (via clinvar/ClinGen)
PIK3CA mutations are associated with hereditary cancer syndromes and sporadic tumors including:
- Hereditary breast cancer (ORPHANET:227535)
- Rare ovarian cancer (ORPHANET:213500)
- Familial prostate cancer (ORPHANET:1331)
- Colorectal cancer, gastric cancer, endometrial cancer, hepatocellular carcinoma, and others
Phenotype Associations
Top 30 HPO (Human Phenotype Ontology) terms associated with PIK3CA:
| HPO ID | Phenotype | Frequency in PIK3CA-related conditions |
|---|---|---|
| HP:0001355 | Megalencephaly | Very common |
| HP:0002126 | Polymicrogyria | Very common |
| HP:0001548 | Overgrowth | Very common |
| HP:0000256 | Macrocephaly | Common |
| HP:0001012 | Multiple lipomas | Common |
| HP:0001028 | Hemangioma | Common |
| HP:0005306 | Capillary hemangioma | Common |
| HP:0001048 | Cavernous hemangioma | Common |
| HP:0002240 | Hepatomegaly | Common |
| HP:0001744 | Splenomegaly | Common |
| HP:0001250 | Seizure | Common |
| HP:0002133 | Status epilepticus | Common |
| HP:0001249 | Intellectual disability | Common |
| HP:0001528 | Hemihypertrophy | Common |
| HP:0005323 | Hemifacial hypertrophy | Common |
| HP:0001159 | Syndactyly | Common |
| HP:0001770 | Toe syndactyly | Common |
| HP:0001829 | Foot polydactyly | Common |
| HP:0002664 | Neoplasm | Common (somatic) |
| HP:0003002 | Breast carcinoma | Associated |
| HP:0003003 | Colon cancer | Associated |
| HP:0001402 | Hepatocellular carcinoma | Associated |
| HP:0002667 | Nephroblastoma | Associated |
| HP:0003006 | Neuroblastoma | Associated |
| HP:0000821 | Hypothyroidism | Associated |
| HP:0001508 | Failure to thrive | Associated |
| HP:0001513 | Obesity | Associated |
| HP:0002019 | Constipation | Associated |
| HP:0001289 | Generalized hypotonia | Associated |
| HP:0002119 | Ventriculomegaly | Associated |
Complex Disease / GWAS Associations
Top 8 GWAS associations (PIK3CA locus on chromosome 3):
| Trait | SNP/Locus | P-value | Association Type |
|---|---|---|---|
| Mean corpuscular volume | PIK3CA chr3 | 4.0×10⁻²³ | Hematologic trait |
| Red blood cell count | PIK3CA chr3 | 2.0×10⁻¹⁶ | Hematologic trait |
| Mean corpuscular hemoglobin | PIK3CA chr3 | 2.0×10⁻¹⁹ | Hematologic trait |
| Mean reticulocyte volume | PIK3CA chr3 | 1.0×10⁻¹⁰ | Hematologic trait |
| Mean spheric corpuscular volume | PIK3CA chr3 | 1.0×10⁻¹¹ | Hematologic trait |
| Reticulocyte fraction of red cells | PIK3CA chr3 | 5.0×10⁻⁹ | Hematologic trait |
| Mean corpuscular hemoglobin | PIK3CA chr3 | 3.0×10⁻⁸ | Hematologic trait (earlier study) |
Note: GWAS associations for PIK3CA are predominantly with red blood cell indices and related hematologic parameters, reflecting common variant effects on erythropoiesis rather than Mendelian disease phenotypes.