The inhibitory role of Mac-1 may have relevance in humans as the non-synonymous Mac-1 functional variant rs1143679 (Arg to His substitution at position 77 in the extracellular β-propeller domain of the CD11b subunit) that increases risk for lupus nephritis decreases Mac-1 ligand binding19,29 by interfering with allostery relay to the ligand binding αI-domain30. Here, ITGAM is linked to lupus nephritis.