Van der Woude syndrome (VWS) shows an autosomal dominant pattern of inheritance with two known candidate genes, IRF6 and GRHL3. In this study, by employing genome-wide linkage analyses on two VWS affected families, we report the cosegregation of an intronic rare variant in NOL4 in one family, and a haplotype consisting of three variants in the noncoding region of IRF6 (introns 1, 8 and 3′ UTR) in the other family. Using mouse, as well as human embryos as a model, we demonstrate the expression of NOL4 in the lip and palate primordia during their development. Luciferase, as well as miRNA-transfection assays show decline in the expression of mutant NOL4 construct due to the creation of a binding site for hsa-miR-4796-5p. In family 2, the noncoding region IRF6 haplotype turns out to be the candidate possibly by diminishing its IRF6 expression to half of its normal activity. Thus, here we report a new candidate gene (NOL4) and a haplotype of IRF6 for VWS, and highlight the genetic heterogeneity of this disorder in the Indian population.