You will recall that with certain arayos, one can violate more than one prohibition with a single act. For example, one can violate simultaneously the prohibitions on relations with one’s mother and with one’s father’s wife (assuming that one’s mother is or has been one’s father’s wife). By necessity, a man who has relations with his father violates the general ban on homosexuality in addition to the specific prohibition regarding a father. Here, too, the case of a father’s brother violates its own specific prohibition in addition to the general injunction proscribing homosexuality. (We haven’t come to the ban on homosexuality yet; that’s coming up in Mitzvah #209.)
This prohibition applies regardless of whether the uncle is the father’s full brother or a half-brother on either side. One may assume that the reason for the additional prohibition is because it is an affront to one’s father, similar to the prohibition against sexual relations with aunts in the previous two mitzvos. A practical ramification of violating two commandments simultaneously is that if the act was committed inadvertently, the offender would be obligated to bring two sin offerings, one for each mitzvah.
While a man may not marry an aunt, a woman is permitted to marry her uncle. In fact, according to at least one opinion, it’s considered meritorious for a man to marry a niece (see Talmud Yevamos 62b and Rambam Hilchos Issuei Bi’ah 2:14). This, however, is generally prohibited by secular law. (Contrary to common misconception, Mordechai and Esther in the Biblical Book of Esther were not uncle and niece; they were first cousins.)
This mitzvah applies in all times and places. It is discussed in the Talmud tractates of Sanhedrin (54a) and Yevamos (54b). It is codified in the Shulchan Aruch in Even Ha’Ezer 15. This prohibition is #352 of the 365 negative mitzvos in the Rambam’s Sefer HaMitzvos and #114 of the 194 negative mitzvos that can be fulfilled today as listed in the Chofetz Chaim’s Sefer HaMitzvos HaKatzar.