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The TGW6 gene encodes a novel indole-3-acetic acid-glucose hydrolase and plays a significant role in improving thousand grain weight (TGW) and yield in rice. In the current study, a TGW6 ortholog from bread wheat chromosome 3AL was isolated and designated as TaTGW6-A1. Sequencing and alignment analysis showed that the cloned TaTGW6-A1 consists of a 987-bp intronless open reading frame. Three single-nucleotide polymorphisms (SNPs) were identified between cultivars with higher and lower TGW, forming two haplotypes, TaTGW6-A1a and TaTGW6-A1b. A derived cleaved amplified polymorphic sequence marker, TaTGW6-A1-CAPS, was developed to differentiate the two haplotypes. Linkage analysis using the wheat 90K iSelect SNP array mapped TaTGW6-A1-CAPS at 18 cM from BobWhite_c47304_56 in a RIL population derived from Zhou 8425B/Chinese Spring. A QTL for yield at the TaTGW6-A1 locus explained 17.4 % of the phenotypic variance in average yield over four environments. Association analysis on 242 Chinese and foreign cultivars indicated that TaTGW6-A1 was significantly associated with TGW. The cumulative frequency of the TaTGW6-A1a allele associated with higher TGW was approximately 80 %, indicating that the TaTGW6-A1a allele was positively selected in wheat breeding. In conclusion, TaTGW6-A1 in conjunction with its molecular marker may contribute as a valuable gene in improving yield potential in wheat. [ABSTRACT FROM AUTHOR]