Table 2.

Proposed APOL1 variant-driven injury mechanisms

Mechanisms	Downstream effects
CXCR3 stimulation via CXCL9, CXCL10, CXCL11	Activation of stress kinases (p44/42 MAPK), phosphoinositide 3-kinase
Opening cation channels	Activation of stress kinases (p44/42 MAPK)
Activation of integrin alpha V beta 3	Altered cell adhesion
Mitochondrial dysfunction	Potential energy deficit., altered metabolic function
Impaired endolysosmal dysfunction	Impaired cell function, possibly premature senescence
NLRP3 inflammasome activation	Generation of IL-1beta, inflammation
PKR activation	Impairment of protein synthesis

Most injury pathways have been studied in cell culture models and a few have been studied in mouse models; hence the relevance of particular mechanisms to human disease states and in particular whether the pathway is of central relevance to human disease pathogenesis remains to be established.