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The Rodl-Kaplice-Blanice fault system (RKB) of Variscan shear origin, repeatedly active since the Late Paleozoic to the Recent, is expressed by a number of lithological contacts, distinct geophysical gradients and many landforms. A general trend of the RKB as well as linear configuration of its internal architecture is fairly similar to those of topical near Rhine Graben and Alpine-Carpathian transition area as the two other consistent recently reactivated large-scale tectonic structures in the extended (thinned) crust of central Europe. In middle part of the RKB, the occurring linear topographic and geological features parallel to the main RKB sections point to the existence of a wide tectonic zone in the crust following the fault system. Our multidisciplinary study includes a summary of corresponding basic geological data, overview of seismic, regional geophysical and geomorphological conditions, primary model of recent kinematic activity in the RKB area derived from the space (Global Navigation Satellite System—GNSS) monitoring and terrestrial (repeated high precision levelling) geodetic data and comparison of these various information. The obtained knowledge indicates that the RKB is active up to ~ 1.0 mm horizontally and > 0.5 mm vertically. The fault system area in the Bohemian Massif can be subdivided into the three parts of diverse tectonic structure and block kinematics. Sinistral horizontal movements are highest near the southern surface sections (Rodl-Kaplice, Rudolfov and Drahotěšice faults), whereas noticeable vertical differentiation is going on mainly along the Blanice and Kouřim faults in the north where the RKB activity is gradually decreasing towards the extensive Elbe shear zone with transverse movements. The middle part of the RKB is dislocated by a large active transverse tectonic structure of the South Bohemian Basins (SBB) with variable horizontal velocity vectors of surface GNSS stations. Most of the weak regional earthquakes have been recorded west of the RKB. Besides faults of the SBB, these were mainly associated with the RKB-subparallel Lhenice fault. Based on the earthquake distribution and foci depths, the latter fault can have similar structural position as the RKB related to lower part of the Variscan level in the ~ 10–12 km depth. [ABSTRACT FROM AUTHOR]