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The ruminant casein gene family ( CSNs , link as CSN1S1 - CSN2 - CSN1S2 - CSN3 ) is characterized by diverse variations and has been extensively studied for ruminant milk traits, however, studies on insertion/deletion (indel) mutations within this gene family and their effects on prolificacy are extremely limited. This study aimed to detect possible novel indels within CSNs in an indigenous Chinese goat breed—Shaanbei White Cashmere goat (SBWC, n = 3047) and four other Chinese goat breeds (n = 1136) with varied litter size rates (105%–283%) and different estrus types (seasonal vs. perennial), as well as exploring the association between these potential indels and litter size. Only one novel 11-bp indel within the CSN1S1 gene was found. The association analyses uncovered that this novel indel was related to the first-birth litter size of SBWC population (n = 2690) ( P  < 1.0 E-8). Individuals with the II genotype (n = 676) had the best litter size when compared with those ID genotype (n = 1098) and DD genotype (n = 916) individuals. Animals with the II genotype were found to have higher relative expression level of CSN1S1 gene in the ovary ( P  < 0.01). Besides, Chi-square tests for different litter size and estrous cycle breeds showed that perennial-estrus breeds and multi-kids breeds had higher “I” allelic frequencies and “II” genotypic frequencies. These findings suggest the 11-bp indel within the CSN1S1 gene is significantly associated with reproduction traits and can be an effective molecular marker for litter size of goat breeding. [ABSTRACT FROM AUTHOR]