MAP3K8 and melanoma: Another gene from this pathway that is often mutated or deregulated in BRAFi-resistant melanomas is MAP3K8. The MAP3K8 gene encodes the MAP3K8 protein (mitogen-activated protein kinase kinase kinase 8, also called COT, EST, ESTF, MEKK8, TPL2, Tpl-2, c-COT and AURA2).