Ask about this productRelated genes to: DPP6 Blocking Peptide
- Gene:
- DPP6 NIH gene
- Name:
- dipeptidyl peptidase like 6
- Previous symbol:
- -
- Synonyms:
- DPPX, DPL1
- Chromosome:
- 7q36.2
- Locus Type:
- gene with protein product
- Date approved:
- 1993-02-11
- Date modifiied:
- 2016-02-08
Related products to: DPP6 Blocking Peptide
Related articles to: DPP6 Blocking Peptide
- Dipeptidyl aminopeptidase-like protein 6 (DPP6) is a subunit of the K4 channels that carry the transient-outward current () in cardiac Purkinje cells (PCs) and ventricular myocytes (VMs). genetic variants have been linked to severe arrhythmia syndromes. Given the influence of other subunits on the Na1.5-mediated cardiac sodium current (), we examined whether DPP6 regulates both and . We explored the impact of the missense variants c.821G>A and c.637C>T, segregating in families with long-QT syndrome (LQTS), and c.2252C>T and c.1578G>C, associated with J-wave syndromes (JWSs) and unexplained syncope. In human and mouse heart slices, DPP6 localized within 40 nanometers of Na1.5. Functionally, DPP6 reduced and increased density in transfected Chinese hamster ovary cells. variants linked to LQTS and JWSs led to a hypo- and hyperinhibition of , respectively. Conversely, was increased by the JWS variants and decreased by the LQTS variants coexpressed with PC (but not VM) subunits. These findings were validated in human induced pluripotent stem cell-derived cardiomyocytes. In silico modeling of and data into PC and VM single-cell action potentials, subsequently integrated in two-dimensional tissue simulations, produced steep repolarization gradients for LQTS-c.821G>A versus slowed conduction for JWS-c.2252C>T. Noninvasive electrocardiographic imaging, used for advanced clinical phenotyping, showed dispersed and prolonged repolarization in the c.821G>A index patient versus right ventricular outflow tract delayed activation of a c.2252C>T carrier. In conclusion, variants play an important role in the mutually antagonistic regulation of and , contributing to cardiac electrophysiology and arrhythmogenesis. - Source: PubMed
Publication date: 2026/04/29
Rossetti AlbertoStoks JobSpätjens Roel L H M GKämmerer SusanneBayer JasonLi XiaofeiKosmidis GeorgiosFirneburg RebeccaSeyen Sandrine R MTer Bekke Rachel M AHelderman-van den Enden Apollonia T J Mvan Tintelen J PeterWilde Arthur A MLoeys BartSaenen JohanHeijman JordiVolders Paul G A - Sleep disturbances are early hallmarks of Alzheimer's disease (AD) and other dementias, yet the molecular mechanisms remain poorly understood. We previously showed that dipeptidyl aminopeptidase-like protein 6-knockout (DPP6-KO) mice exhibit accelerated neurodegeneration with synaptic loss, neuronal death, and circadian dysfunction resembling AD pathology. Here, we investigate whether DPP6 deficiency directly causes sleep dysregulation and assess age-dependent effects using wireless EEG/EMG telemetry, behavioral monitoring, and body temperature recordings. We found striking age-dependent sleep phenotypes in DPP6-KO mice. Adult (3-month) DPP6-KO mice showed hyperactivity-driven REM sleep increases, while aged (12-month) DPP6-KO mice developed insomnia with fragmented sleep architecture. Critically, aged DPP6-KO mice exhibited decreased REM latency, a biomarker of depression, which we confirmed by behavioral assays. Conversely, DPP6 overexpression in aged wild-type mice increased NREM duration and reduced sleep fragmentation, demonstrating a protective effect. Throughout aging, DPP6-KO mice showed dysregulated locomotor activity and body temperature rhythms, suggesting broader disruption of circadian and metabolic homeostasis. These findings establish DPP6 as a critical regulator of sleep architecture whose loss recapitulates key sleep disturbances observed in AD/dementia. The progressive nature of sleep dysfunction in DPP6-KO mice, from REM abnormalities to insomnia, parallels human disease progression and positions DPP6 as a potential therapeutic target for sleep-related symptoms in neurodegenerative disorders. - Source: PubMed
Publication date: 2026/04/02
Lin LinPratt Ashley EHoffman Dax A - The gene DPP6 has been associated with behavioral phenotypes of alcohol use disorder (AUD) in recent human genome-wide association studies. DPP6 encodes an auxiliary subunit that modulates A-type voltage-gated potassium channels, particularly Kv4.2. - Source: PubMed
Hernández MaribelBarkley-Levenson Amanda M - A number of published studies suggest that HIV infection accelerates epigenetic ageing. The main aim of this study was to ascertain if HIV infection is an independent factor leading to DNA hypomethylation and accelerating epigenetic ageing in men successfully treated with integrase inhibitor (INSTI)-based combined antiretroviral therapy (cART). Forty-eight (48) men living with HIV receiving INSTI-based cART and fifty (50) uninfected men in the control group were included. All participants filled out a questionnaire probing into lifestyle factors. Global and site-specific DNA methylation and expression of methyltransferase genes were examined in all participants. As well, all patients underwent basic laboratory blood tests. The results were analysed using statistical and machine learning methods. We found a strong association between HIV infection and global DNA hypomethylation as well as significant association with higher expression of the methyltransferase gene . However, there was no association with DNA methylation levels of CNOT2, DPP6, FOXG1 and NPTX2 genes or expression levels of and . The results confirm that in men successfully treated with INSTI-based cART, HIV infection is an independent factor causing global DNA hypomethylation and increased expression and thus accelerating epigenetic ageing. - Source: PubMed
Publication date: 2026/02/02
Bożejko MateuszMałodobra-Mazur MałgorzataGnatowski AndrzejOłdakowska MonikaSzymczak AleksandraSzetela BartoszCiepłucha HubertZińczuk AleksanderKnysz Brygida - Younger-onset type 2 diabetes (T2D) (onset <40 years) represents a growing global health challenge, characterized by heterogenous pathophysiology and accelerated complications. Current one-size-fits-all treatment approaches may be inadequate for this population. To address this heterogeneity, we performed clinical variable-based clustering using BMI, onset age, HbA1c, and HOMA2 indices in 717 participants across discovery and validation cohorts. Three distinct subgroups were identified: mild obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD), and severe insulin-resistant diabetes with insulin insufficiency (SIRD-II). Over median follow-up of 2.8 years, SIRD-II demonstrated 11-fold increased risk of progressive chronic kidney disease, while both SIDD and SIRD-II showed threefold increased risk for progressive albuminuria compared with MOD. SIRD-II also demonstrated 3.5-fold and 2.3-fold higher 10-year cardiovascular risk compared with SIDD and MOD respectively. Metabolomic analysis revealed distinct signatures: SIDD exhibited lower levels of lipids, amino acids, and inflammatory markers, while SIRD-II demonstrated elevated glucose, lipids, and branched-chain amino acids, suggesting glucolipotoxicity. Proteomics analysis validated previously reported biomarkers (IGFBP1, RTN4R, PLXNB2) and identified additional molecules (CDHR2, ERBB4, DPP6) that may shed light on disease mechanisms. In conclusion, younger-onset T2D exhibits distinct subgroups with differential pathobiology, molecular signatures, and clinical outcomes, suggesting the need for personalised precision diabetes care. - Source: PubMed
Tan Clara Si HuaKee Kai XiangZheng HuiliWong Kay Wye SabrinaChan Wan Ting LovynnSong YuzhenAng KevenSubramaniam TavintharanSum Chee FangLim Su Chi