Catalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-deoxy-D-mannose. GDP-alpha-D-mannose = GDP-4-dehydro-alpha-D-rhamnose + H2O Inhibited by GDP-fucose. Nucleotide-sugar biosynthesis; GDP-L-fucose biosynthesis via de novo pathway; GDP-L-fucose from GDP-alpha-D-mannose: step 1/2. Highly expressed in pancreas and small intestine. Expressed in thymus, protstate, colon, heart, placenta, liver and kidney. Expressed at low levels in spleen, testis, brain and lung. Belongs to the NAD(P)-dependent epimerase/dehydratase family. GDP-mannose 4,6-dehydratase subfamily. Truncated N-terminus.