Mutations in super-enhancers have been noted in various diseases, including cancers, type 1 diabetes, Alzheimer’s disease, lupus, rheumatoid arthritis, multiple sclerosis, systemic scleroderma, primary biliary cirrhosis, Crohn’s disease, Graves disease, vitiligo, and atrial fibrillation.  A similar enrichment in disease-associated sequence variation has also been observed for stretch enhancers.
Super-enhancers may play important roles in the misregulation of gene expression in cancer. During tumor development, tumor cells acquire super-enhancers at key oncogenes, which drive higher levels of transcription of these genes than in healthy cells. Altered super-enhancer function is also induced by mutations of chromatin regulators. Acquired super-enhancers may thus be biomarkers that could be useful for diagnosis and therapeutic intervention.
Proteins enriched at super-enhancers include the targets of small molecules that target transcription-regulating proteins and have been deployed against cancers. For instance, super-enhancers rely on exceptional amounts of CDK7, and, in cancer, multiple papers report the loss of expression of their target genes when cells are treated with the CDK7 inhibitor THZ1. Similarly, super-enhancers are enriched in the target of the JQ1 small molecule, BRD4, so treatment with JQ1 causes exceptional losses in expression for super-enhancer—associated genes.