ABCC11 is a gene encoding an apical ATP-driven efflux transporter that has been found to transport a variety of lipophilic anions including cyclic nucleotides, estradiol glucuronide, steroid sulfates such as DHEA-S, and monoanionic bile acids. It is expressed and localized in apocrine glands, including in the axilla, the ceruminous glands in the auditory canal, and in the mammary gland. A single-nucleotide polymorphism (SNP) 538G→A in ABCC11 that leads to a G180R substitution in the encoded protein has been found to result in loss-of-function via affecting N-linked glycosylation and in turn causing proteasomal degradation of the protein. This polymorphism has been found to be responsible for the dry and white earwax phenotype, and is considered to be unique as it has been described as the only human SNP that has been found to determine a visible genetic trait. In addition to earwax phenotype, the ABCC11 genotype has been found to be associated with colostrum secretion from the breasts as well as normal axillary odor and osmidrosis (excessive axillary malodor).
A functional ABCC11 protein has been found to be essential for the presence of the characteristic strong axillary odor, with the 538G→A SNP leading to a loss of secretion of axillary malodorous precursors and a nearly complete loss of axillary odor in those who are homozygous for the polymorphism. Specifically, the secretion of the amino-acid conjugates 3M2H-Gln, HMHA-Gln, and Cys-Gly-(S) 3M3SH, which are precursors of key axillary malodorous compounds including the unsaturated or hydroxylated branched-chain fatty acids 3M2H and HMHA and the sulfanylalkanol 3M3SH, has been found to be abolished in homozygotic carriers of the SNP, and the odoriferous androstane steroids androstenone and androstenol and their precursors DHEA and DHEA-S have been found to be significantly reduced as well. Patients with axillary osmidrosis (538G/G or 538G/A genotype) were found to have significantly more numerous and relatively large axillary apocrine glands compared to controls with the A/A genotype.