{"doi":"10.1172/jci.insight.138057","title":"A KCNK16 mutation causing TALK-1 gain of function is associated with maturity-onset diabetes of the young","abstract":"Maturity-onset diabetes of the young (MODY) is a heterogeneous group of monogenic disorders of impaired pancreatic β cell function. The mechanisms underlying MODY include β cell KATP channel dysfunction (e.g., KCNJ11 [MODY13] or ABCC8 [MODY12] mutations); however, no other β cell channelopathies have been associated with MODY to date. Here, we have identified a nonsynonymous coding variant in KCNK16 (NM_001135105: c.341T>C, p.Leu114Pro) segregating with MODY. KCNK16 is the most abundant and β cell-restricted K+ channel transcript, encoding the two-pore-domain K+ channel TALK-1. Whole-cell K+ currents demonstrated a large gain of function with TALK-1 Leu114Pro compared with TALK-1 WT, due to greater single-channel activity. Glucose-stimulated membrane potential depolarization and Ca2+ influx were inhibited in mouse islets expressing TALK-1 Leu114Pro with less endoplasmic reticulum Ca2+ storage. TALK-1 Leu114Pro significantly blunted glucose-stimulated insulin secretion compared with TALK-1 WT in mouse and human islets. These data suggest that KCNK16 is a previously unreported gene for MODY.","journal":"JCI Insight","year":2021,"id":167339,"datarank":0.5244761342199721,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.0,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":694238,"name":"Stephanie Johnson","orcid":"0000-0003-4540-2751","position":1,"is_corresponding":false},{"id":293025,"name":"Paul Leo","orcid":"0000-0001-8325-4134","position":2,"is_corresponding":false},{"id":369839,"name":"Prasanna K. Dadi","orcid":"0000-0001-5377-5991","position":3,"is_corresponding":false},{"id":346921,"name":"Matthew T. Dickerson","orcid":"0000-0002-6187-3951","position":4,"is_corresponding":false},{"id":370584,"name":"Arya Y. Nakhe","orcid":null,"position":5,"is_corresponding":false},{"id":501405,"name":"Aideen McInerney‐Leo","orcid":"0000-0002-0059-5732","position":6,"is_corresponding":false},{"id":694708,"name":"Mhairi Marshall","orcid":null,"position":7,"is_corresponding":false},{"id":345676,"name":"Karolina E. Zaborska","orcid":"0000-0003-1218-5228","position":8,"is_corresponding":false},{"id":369841,"name":"Charles M. Schaub","orcid":"0000-0002-3251-3455","position":9,"is_corresponding":false},{"id":22039,"name":"Matthew A. Brown","orcid":"0000-0003-0538-8211","position":10,"is_corresponding":false},{"id":345680,"name":"David A. Jacobson","orcid":"0000-0003-1816-5375","position":11,"is_corresponding":false},{"id":85479,"name":"Emma L. Duncan","orcid":"0000-0002-8143-4403","position":12,"is_corresponding":false},{"id":369840,"name":"Sarah M. Graff","orcid":"0000-0003-2408-3683","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:45:54.042727Z","pmid":"34032641","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":[]}