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Hypoxia-inducible factor (HIF) is one of the most important factors in the cellular response to hypoxia, transcriptionally activating genes encoding proteins that mediate adaptive responses to reduced oxygen availability. HIF is a heterodimer consisting of one of three subunits, HIF1 alpha, HIF2 alpha, or HIF3 alpha. HIF target genes play critical roles in metabolism, angiogenesis, cell proliferation and cell survival. HIF3 alpha protein is one of several alpha/beta-subunit heterodimeric transcription factors that regulate many adaptive responses to low oxygen tension (hypoxia). The alpha 3 subunit lacks the transactivation domain found in factors containing either the alpha 1 or alpha 2 subunits. HIF3 alpha may be a marker for tumor growth and angiogenesis.