We show here that N-terminal TSHZ3 variants affect binding of SOX9 and MYOCD, providing a pathomechanism by which TSHZ3 missense variants may lead to disrupted SM cell differentiation, as suggested by α-SMA immunohistochemistry on a nephrectomy specimen of a TSHZ3 variant carrier with MCDK, hydronephrosis and hydroureter, and previously shown in the proximal ureter of Tshz3-null mutant mice [20]. The gene discussed is TSHZ3; the disease is hydronephrosis.