Table 1

 Putative function of the different mutations in the coding region of the MC4R gene segregating in the 26 families according to different assays

Amino acid position and changeCell surface expressionLigand bindingSignalling properties as measured by cAMP (α-MSH) assay
IC50Specific binding (relative to WT)
*The Y35X and D37V mutations only occur together on a haplotype and thus are not analysed separately;†The G181D mutation only occurred in an extremely obese index patient but not in his two available relatives and could therefore not be included in the statistical analysis.
LOF, loss of function; RF, reduced function.
S30FAbout 120%31Like WT,23 RF31
[Y35X, D37V]*LOF31
P78L31%,31 1%,32 0%34About 10%32RF,23 LOF,31 LOF34
S94RLOF23
V95ILOF23
T112M41%,32 like WT35Sign. reduced32Like WT,29 like WT35
I121TRF23
S127L101%,31 like WT35Const. active,23 RF,31 RF35
R165W26%,31 9%32About 0%10RF10
G181D†LOF23
L211fsX2160%300%30LOF,23 LOF,31 LOF30
P230LConst. active 23
A244E90%31RF,23 RF31
L250fsX284LOF23
G252SAbout 100%31Like WT,23 RF31
I317T66%,31 42%,32 reduced33About 42%32Like WT,23 RF,31 RF33
Y320fsX354RF23