Band 3 Missense Mutations and Stomatocytosis: Insight into the Molecular Mechanism Responsible for Monovalent Cation Leak

Table 1

Features of cation leaky red cells and point-mutated AE1.

AE1 point mutation	Red cell shape	Abundance of AE1 (band 3) in red cell membrane^1	Red cell cation leak rate at 0°C (multiple of normal)^1	Anion exchange activity of mutated AE1^2	Pharmacology of the red cell cation leak	Pharmacology of the cation leak in heterologous expression system (cation conductance or cation flux)
L687P	Stomatocyte	82%	7-8	Abolished	NS1652, SITS, dipyridamol	Cation conductance: SITS, Zn^2+, La^3+ sensitive
D705Y	Spherocyte	77%	8	Abolished	NS1652, SITS, dipyridamol	Cation conductance: SITS, Zn^2+, La^3+ sensitive
R730C	Stomatocyte	Normal	6 (at 37°C)	Abolished	NT	NT
S731P	Stomatocyte	79%	30–57-58–87	Abolished	NS1652, SITS, dipyridamol	Cation conductance: SITS, Zn^2+, La^3+ sensitive
H734R	Stomatocyte	74–82%	87–94	Abolished	NS1652, SITS, dipyridamol	Cation conductance: SITS, Zn^2+, La^3+ sensitive
E758K	Spherostomatocyte	Mild deficiency	NT	Normal with GPA coexpression	NT	Rb flux: DIDS, Zn^2+, Gd^3+ sensitive. Conductance: Zn^2+, SITS and WW-781 sensitive
R760Q	Spherocyte	85–92%	4–6	74% of wt (with GPA)	NS1652, SITS, dipyridamol	NT
S762R	Stomatocyte	NT	7	Abolished	NT	NT
G796R	Stomatocyte	Normal	NT	Abolished	NT	Li uptake insensitive to SITS or H2DIDS

This table summarized data collected from different publications. For L687P, D705Y, S731P, H734R, [20, 25]. For R730C, [23]. For E758K, [24]. For R760Q, [20, 31]. For S762R, [21]. For G796R, [22]. NT: not tested.
¹Each number refers to features of red cells from different patients carrying the same AE1 mutation.
²The anion exchange was assessed in amphibian oocyte expressing the mutated AE1. The loss of anion exchange is confirmed in heterozygote red cells by ≈50% decreased anion flux.