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Signature of selection studies have identified many genomic regions with known functional importance and some without verified functional roles. Multiple studies have identified Transmembrane protein 8B (<i>TMEM8B)</i><i>rs426272889</i> as having been recently under extreme selection pressure in domesticated sheep, but no study has provided sheep phenotypic data clarifying a reason for extreme selection. We tested <i>rs426272889</i> for production trait association in 770 U.S. Rambouillet, Targhee, Polypay, and Suffolk sheep. <i>TMEM8B</i><i>rs426272889</i> was associated with mature weight at 3 and 4 years (<i>p</i> < 0.05). This suggested selection for sheep growth and body size might explain the historical extreme selection pressure in this genomic region. We also tested Sperm-associated antigen 8 (<i>SPAG8</i>) <i>rs160159557</i> encoding a G493C substitution. While this variant was associated with mature weights at ages 3 and 4, it was not as strongly associated as <i>TMEM8B</i><i>rs426272889.</i> Transmembrane protein 8B has little functional information except as an inhibitor of cancer cell proliferation. To our knowledge, this is the first study linking <i>TMEM8B</i> to whole organism growth and body size under standard conditions. Additional work will be necessary to identify the underlying functional variant(s). Once identified, such variants could be used to improve sheep production through selective breeding.