Table 1.

Table of human leptin variants studied

Human leptin variant	Residue # after signal peptide cleavage	Publication	Impact	RUSH results		Additional details
				Expression	Secretion
G59S	G38S	Bouafi et al., Biomed Res Int. 2019 (43); Funcke, J et al. N. Engl. J. Med. 2023 (16)	Reduced receptor affinity	↔	↔	Possible reduction in secretion
L72S	L51S	Fischer-Posovszky et al., J Clin Endocrinol Metab. 2010 (25)	Undetectable serum leptin	↓↓↓↓	N/A (low expression)	Proteasomal degradation
N103K	N82K	Mazen et al., Mol Genet Metab. 2009; (26) Bouafi et al., Biomed Res Int. 2019 (43)	Reduced serum leptin	↔	↔	No effect found
R105W	R84W	Strobel et al.,Nat Genet. 1998; (12) Saeed et al.,Obesity. 2015; (27) Bouafi et al., Biomed Res Int. 2019 (43)	Reduced/undetectable serum leptin	↓↓↓↓	N/A (low expression)	Proteasomal degradation
C117Y	C96Y	Saeed et al.,Obesity. 2015; (27) Bouafi et al., Biomed Res Int. 2019 (43)	Undetectable serum leptin	↓↓↓↓	N/A (low expression)	Proteasomal degradation
H118L	H97L	Zhao et al., Biomed Res Int. 2014 (30)	No data	↔	↔	Possible reduction in expression and secretion
P23R	P2R	Murray et al., Eur J Endocrinol. 2011 (28)	Reduced serum leptin (possibly confounded by decreased antibody binding)	↔	↔	No effect found
P64S	P43S	Funcke, J et al. N. Engl. J. Med. 2023 (16)	Reduced receptor affinity	↔	↔	No effect found
D100Y	D79Y	Wabitsch et al., N Eng J Med. 2015 (13)	Reduced receptor affinity	↔	↔	No effect found
D100N	D79N	Bouafi et al., Biomed Res Int. 2019 (43); Saeed et al., Diabates. 2020 (31)	No data	↔	↔	Possible reduction in expression
V110M	V89M	Echwald et al., Int J Obesity. 1997 (32)	No effect on serum leptin	↔	↔	No effect found
S141C	S120C	Chekhranova et al., Bioorg Khim. 2008 (29)	No data	↔	↓↓↓↓	Secretion reduction by approximately 50%