Table 1.

Ion transport proteins in human pigmentation.

Proteins	Substrates	Localization	Genetic disorder	A) Pathogenic mutationsa B) Polymorphismsb	Phenotypesc
OCA2/P	Cl−?	Melanosome stages III–IV	Type II OCA	A) V443I, A481T, P743L B) R305W, R419Q	A) Skin and hair hypopigmentation, reduced iris and retinal pigments, and ocular defect B) Blue/green/hazel eye colors
SLC45A2/MATP/AIM1	H+/sugar co-transport?	Melanosome stages III–IV	Type IV OCA	A) D93N, D157N, G188V, T437A, T440A, A477T B) E272K/K272E, F374L/L374F	A) Light/yellow/white/blue hairs, blue/red/brown/gray eye colors, and some nystagmus. B) Blue/green/hazel/brown eye colors, olive/brown/ black skin, black/brown/blond/red hair
SLC24A5/NCKX5	Na+/Ca2+ and K+ antiport?	TGN Mitochondria (Melanosome?)	Type VI OCA	A) A115E, R174K, S182R, W197X B) T111A/A111T	A) White skin, brown hair, brown iris, and underdeveloped macula B) Light skin pigmentation
TPC2/TPCN2	Ca2+ or Na+?	Melanosome stages III–IV *Multiple organelles	–	B) G734E, M484L	B) Blond hair
ATP7A/MNK	Cu2+	TGN Melanosome stages III–IV	Menkes disease	A) E628V, S653Y, C1002F	A) Broad phenotypes. Severe defect leads to death. Classical phenotypes: growth failure, Kinky hair, nervous system deterioration
V-ATPase	H+	Melanosome (all stages) *Multiple organelles	–	–	–

OCA, oculocutaneous albinism; TGN, trans-Golgi network.

^aExamples of pathogenic mutations.

^bExamples of non-pathogenic polymorphisms.

^cExamples of phenotypes which are corresponded to either pathogenic mutations (A) or non-pathogenic polymorphism (B).