{"doi":"10.3389/fimmu.2020.617464","title":"Editorial: Human Disorders of PI3K Biology","abstract":"The aim of this Research Topic was to bring together experts in basic, translational, and clinical research relating to phosphoinositide 3-kinase (PI3K) biology. The monogenic human immune disease \"Activated PI3Kd Syndrome\" (APDS) has shed new light on immune functions of this kinase as well as its therapeutic targeting. PI3Ks have pleotropic effects across all cell types by phosphorylating PtdIns(4,5)P 2 to generate PtdIns(3,4,5)P 3 , a second messenger that recruits and activates signaling proteins to trigger cell growth, proliferation, and survival. PI3Kd is comprised of the p110d catalytic and the p85a regulatory subunits, encoded by PIK3CD and PIK3R1, respectively. This kinase complex can be targeted by multiple small molecule inhibitors, many of which are currently at various stages of clinical development. Heterozygous variants in PIK3CD or PIK3R1 have been found to cause APDS, primarily by affecting inhibitory contacts between the two proteins. Defining the genetic etiology of this disorder has enabled rational targeted therapy to tune down PI3Kd signaling.","journal":"Frontiers in Immunology","year":2020,"id":124236,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9639,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":104185,"name":"Stuart G. Tangye","orcid":"0000-0002-5360-5180","position":1,"is_corresponding":false},{"id":241314,"name":"C. Lucas","orcid":"0000-0002-5754-0820","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:15:07.789881Z","pmid":"33329612","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}