The Cabibbo-Kobayashi-Maskawa (CKM) mixing matrix and flavor-changing neutral currents (FCNCs) in the quark sector are examined in the GUT inspired $SO(5) times U(1) times SU(3)$ gauge-Higgs unification in which the 4D Higgs boson is identified with the Aharonov-Bohm phase in the fifth dimension. Gauge invariant brane interactions play an important role for the flavor mixing in the charged-current weak interactions. The CKM matrix is reproduced except that the up quark mass needs to be larger than the observed one. FCNCs are naturally suppressed as a consequence of the gauge invariance, with a factor of order $10^{-6}$. It is also shown that induced flavor-changing Yukawa couplings are extremely small.
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