ABCC11

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). The ABCC11 transporter is a member of the MRP subfamily which is involved in multi-drug resistance. The product of this gene participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides. In addition, a single nucleotide polymorphism (SNP) in this gene is responsible for determination of human earwax type and presence of underarm odour. This gene and family member ABCC12 are determined to be derived by duplication and are both localized to chromosome 16q12.1. Multiple alternatively spliced transcript variants have been described for this gene.{{cite web | title = Entrez Gene: ABCC11 ATP-binding cassette, sub-family C (CFTR/MRP), member 11| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=85320}}

File:ABCC11 genmap 01.svg

The ABCC11 gene is present in the human genome as two alleles, differing in one nucleotide also known as a single nucleotide polymorphism (SNP).{{cite journal | vauthors = Toyoda Y, Sakurai A, Mitani Y, Nakashima M, Yoshiura K, Nakagawa H, Sakai Y, Ota I, Lezhava A, Hayashizaki Y, Niikawa N, Ishikawa T | title = Earwax, osmidrosis, and breast cancer: why does one SNP (538G>A) in the human ABC transporter ABCC11 gene determine earwax type? | journal = FASEB Journal | volume = 23 | issue = 6 | pages = 2001–13 | date = Jun 2009 | pmid = 19383836 | doi = 10.1096/fj.09-129098 | doi-access = free | s2cid = 26853548 }} A SNP in the ABCC11 gene on chromosome 16 at base position 538 of either a guanine or adenine determines two distinct groups of phenotypes. These respectively code for glycine and arginine in the gene's protein product. Dominant inheritance of the GG or GA genotype is observed while the AA genotype is recessive. The phenotypes expressed by the genotypes include cerumen type (wet or dry ear wax), osmidrosis (odor associated with sweat caused by excessive apocrine secretion), and possibly breast cancer risk, although there is ongoing debate on whether there is a real correlation of the wet ear wax phenotype to breast cancer susceptibility.{{cite journal | vauthors = Rodriguez S, Steer CD, Farrow A, Golding J, Day IN | title = Dependence of deodorant usage on ABCC11 genotype: scope for personalized genetics in personal hygiene | journal = The Journal of Investigative Dermatology | volume = 133 | issue = 7 | pages = 1760–7 | date = Jul 2013 | pmid = 23325016 | pmc = 3674910 | doi = 10.1038/jid.2012.480 }}{{cite journal | vauthors = Park YJ, Shin MS | title = What is the best method for treating osmidrosis? | journal = Annals of Plastic Surgery | volume = 47 | issue = 3 | pages = 303–9 | date = Sep 2001 | pmid = 11562036 | doi=10.1097/00000637-200109000-00014| s2cid = 25590802 }} The GG or GA genotype produces the wet ear wax phenotype (sticky and brown colored) and acrid sweat odor and is the dominant allele. Note this phenotype requires only the presence of one guanine. The homozygous recessive AA genotype produces the dry ear wax phenotype (dry and flaky) and mildly odored sweat.

The alleles containing a guanine produce a protein that is glycosylated but alleles containing an adenine are not glycosylated. The resulting protein is only partially degraded by proteasomes. This effect is localized to ceruminous gland membranes. Because the adenine containing allele protein product is only partially degraded, the remaining functional protein is located on the cell surface membrane which ABCC11 gene's role in sweat odor is likely in part due to the quantitative dosage of ABCC11 protein.

From an evolutionary perspective, the implications of cerumen type on fitness are unknown. However, odorless sweat in ancient Northern Eurasian populations has been postulated to have an adaptive advantage for cold weather. In some nonhuman mammals, mating signals via release of an odor enhanced by increased apocrine secretion may be a factor in sexual selection.

Physical human traits that are controlled by a single gene are uncommon. Most human characteristics are controlled by multiple genes (polygenes); ABCC11 is a peculiar example of a gene with unambiguous phenotypes that is controlled by a SNP. Additionally, it is considered a pleiotropic gene.

File:World map ABCC11 A Allele.svg

The history of the migration of humans can be traced back using the ABCC11 gene alleles. The variation between ear wax in ethnicities around the world are specifically due to the ABCC11 gene alleles.

Some hypotheses propose that the A allele of ABCC11, rs17822931, may confer adaptive advantages in colder climates. The mutation allows for better body heat preservation because it is characterized by diminished sweat gland activity. The mutation emerged approximately 44,000 years ago in a lineage related to the Ust'-Ishim man in the Omsk Oblast of western Siberia. In East Asia, the derived allele appears approximately 40,000 years ago in Northern China among individuals related to the Tianyuan man. In North America, the derived allele appears approximately 12,000 years ago.{{Cite journal |last1=Su |first1=Haoran |last2=Wang |first2=Mengge |last3=Li |first3=Xiangping |last4=Duan |first4=Shuhan |last5=Sun |first5=Qiuxia |last6=Sun |first6=Yuntao |last7=Wang |first7=Zhiyong |last8=Yang |first8=Qingxin |last9=Huang |first9=Yuguo |last10=Zhong |first10=Jie |last11=Chen |first11=Jing |last12=Jiang |first12=Xiucheng |last13=Ma |first13=Jinyue |last14=Yang |first14=Ting |last15=Liu |first15=Yunhui |date=2024-06-18 |title=Population genetic admixture and evolutionary history in the Shandong Peninsula inferred from integrative modern and ancient genomic resources |journal=BMC Genomics |volume=25 |issue=1 |pages=611 |doi=10.1186/s12864-024-10514-9 |doi-access=free |issn=1471-2164 |pmc=11184692 |pmid=38890579}} The gene may have spread as a result of it being a beneficial adaption or through an evolutionary neutral mutation mechanism that went through genetic drift events, or through sexual selection.{{cite journal |vauthors=Martin A, Saathoff M, Kuhn F, Max H, Terstegen L, Natsch A |date=February 2010 |title=A functional ABCC11 allele is essential in the biochemical formation of human axillary odor |journal=The Journal of Investigative Dermatology |volume=130 |issue=2 |pages=529–540 |doi=10.1038/jid.2009.254 |pmid=19710689 |s2cid=36754463 |doi-access=free}}

An analysis of ancient DNA from Eastern European hunter gatherers, Scandinavian Hunter Gatherers, Western Hunter Gatherers and Early European Farmers found that the derived allele of ABCC11 associated with dry earwax and reduced body odor was absent in all European hunter gatherers, except for a Western Hunter Gatherer from Mesolithic central Europe. The derived allele was absent in the Paleolithic hunter gatherer Kostenki 14, who is deeply related to Ancient North Eurasians.{{cite journal |last1=Günther |first1=T |last2=Malmström |first2=H |last3=Svensson |first3=EM |title=Population genomics of Mesolithic Scandinavia: Investigating early postglacial migration routes and high-latitude adaptation. |journal=PLOS Biology |date=January 2018 |volume=16 |issue=1 |pages=e2003703 |doi=10.1371/journal.pbio.2003703 |pmid=29315301 |pmc=5760011 |doi-access=free }} From [https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.2003703.s013 Supporting Information file S8], page 17/28: "Furthermore, SF9, SBj, Hum2 and SF12 as well as all other HG tested (with the exception of KO1), carried allelic variants at ABCC1 gene associated with wet earwax, normal body odor and normal

colostrum [69]." See also: [https://journals.plos.org/plosbiology/article/file?type=supplementary&id=10.1371/journal.pbio.2003703.s001 Supporting Information File S1]

The frequency of alleles for dry ear wax is most concentrated in East Asia; most notably China, Japan, Korea, and Mongolia. The allele frequency is highest among the northern Han Chinese and Koreans; followed by Mongols, southern Han Chinese, and Yamato Japanese, respectively. The frequency is low among the Ryukyuans and Ainu compared to other East Asians.{{cite journal | vauthors = Yoshiura K, Kinoshita A, Ishida T, Ninokata A, Ishikawa T, Kaname T, Bannai M, Tokunaga K, Sonoda S, Komaki R, Ihara M, Saenko VA, Alipov GK, Sekine I, Komatsu K, Takahashi H, Nakashima M, Sosonkina N, Mapendano CK, Ghadami M, Nomura M, Liang DS, Miwa N, Kim DK, Garidkhuu A, Natsume N, Ohta T, Tomita H, Kaneko A, Kikuchi M, Russomando G, Hirayama K, Ishibashi M, Takahashi A, Saitou N, Murray JC, Saito S, Nakamura Y, Niikawa N | title = A SNP in the ABCC11 gene is the determinant of human earwax type | journal = Nature Genetics | volume = 38 | issue = 3 | pages = 324–30 | date = Mar 2006 | pmid = 16444273 | doi = 10.1038/ng1733 | s2cid = 3201966 |url = https://www.nature.com/articles/ng1733| url-access = subscription }} As the mutation was already present in the Tianyuan man of Northern China, this suggests the genetic continuity of the variant in East Asia for the last 40,000 years.{{Cite journal |last=Gelabert |first=Pere |last2=Blazyte |first2=Asta |last3=Chang |first3=Yongjoon |last4=Fernandes |first4=Daniel M. |last5=Jeon |first5=Sungwon |last6=Hong |first6=Jin Geun |last7=Yoon |first7=Jiyeon |last8=Ko |first8=Youngmin |last9=Oberreiter |first9=Victoria |last10=Cheronet |first10=Olivia |last11=Özdoğan |first11=Kadir T. |last12=Sawyer |first12=Susanna |last13=Yang |first13=Songhyok |last14=Greytak |first14=Ellen McRae |last15=Choi |first15=Hansol |date=2022-08-08 |title=Northeastern Asian and Jomon-related genetic structure in the Three Kingdoms period of Gimhae, Korea |url=https://www.sciencedirect.com/science/article/pii/S0960982222009162 |journal=Current Biology |volume=32 |issue=15 |pages=3232–3244.e6 |doi=10.1016/j.cub.2022.06.004 |issn=0960-9822|doi-access=free }} After East Asians, the Indigenous peoples of the Americas exhibit the highest frequency of this mutation.{{Cite journal |last1=Su |first1=Haoran |last2=Wang |first2=Mengge |last3=Li |first3=Xiangping |last4=Duan |first4=Shuhan |last5=Sun |first5=Qiuxia |last6=Sun |first6=Yuntao |last7=Wang |first7=Zhiyong |last8=Yang |first8=Qingxin |last9=Huang |first9=Yuguo |last10=Zhong |first10=Jie |last11=Chen |first11=Jing |last12=Jiang |first12=Xiucheng |last13=Ma |first13=Jinyue |last14=Yang |first14=Ting |last15=Liu |first15=Yunhui |date=2024-06-18 |title=Population genetic admixture and evolutionary history in the Shandong Peninsula inferred from integrative modern and ancient genomic resources |journal=BMC Genomics |volume=25 |issue=1 |pages=611 |doi=10.1186/s12864-024-10514-9 |issn=1471-2164 |pmc=11184692 |pmid=38890579 |doi-access=free}} The derived allele is not rare in South Asia, with 54% of Dravidian people from Tamil Nadu carrying an AA genotype. A downward gradient of dry ear wax allele phenotypes can be drawn from northern China to southern Asia and an east–west gradient can also be drawn from eastern Siberia to western Europe. The allele frequencies within ethnicities continued to be maintained because the ABCC11 gene is inherited as a haplotype, a group of genes or alleles that tend to be inherited as a single unit.{{cite journal | vauthors = Prokop-Prigge KA, Mansfield CJ, Parker MR, Thaler E, Grice EA, Wysocki CJ, Preti G | title = Ethnic/racial and genetic influences on cerumen odorant profiles | journal = Journal of Chemical Ecology | volume = 41 | issue = 1 | pages = 67–74 | date = Jan 2015 | pmid = 25501636 | pmc = 4304888 | doi = 10.1007/s10886-014-0533-y | bibcode = 2015JCEco..41...67P }}

The amount of volatile organic compounds (VOCs) in ear wax was found to be related to variation in ABCC11 genotype, which in turn is dependent on ethnic origin. In particular, the rs17822931 genotype, which is especially prevalent in East Asians, is correlated with lower VOC levels. However, VOC levels were not found to vary significantly qualitatively nor quantitatively for most organic compounds by racial group after Bonferroni corrections, suggesting that it does not result in ethnic differences.{{cite journal | vauthors = Prokop-Prigge KA, Greene K, Varallo L, Wysocki CJ, Preti G | title = The Effect of Ethnicity on Human Axillary Odorant Production | journal = Journal of Chemical Ecology | volume = 42 | issue = 1 | pages = 33–9 | year = 2016 | pmid = 26634572 | pmc = 4724538 | doi = 10.1007/s10886-015-0657-8 | bibcode = 2016JCEco..42...33P }}

• ATP-binding cassette transporter
• Body odor

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• {{cite journal | vauthors = Bera TK, Lee S, Salvatore G, Lee B, Pastan I | title = MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer | journal = Molecular Medicine | volume = 7 | issue = 8 | pages = 509–16 | date = Aug 2001 | pmid = 11591886 | pmc = 1950066 | doi = 10.1007/BF03401856}}
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• {{cite journal | vauthors = Lai L, Tan TM | title = Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues | journal = The Biochemical Journal | volume = 361 | issue = Pt 3 | pages = 497–503 | date = Feb 2002 | pmid = 11802779 | pmc = 1222332 | doi = 10.1042/0264-6021:3610497 }}
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• {{cite journal | vauthors = Guo Y, Kotova E, Chen ZS, Lee K, Hopper-Borge E, Belinsky MG, Kruh GD | title = MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2',3'-dideoxycytidine and 9'-(2'-phosphonylmethoxyethyl)adenine | journal = The Journal of Biological Chemistry | volume = 278 | issue = 32 | pages = 29509–14 | date = Aug 2003 | pmid = 12764137 | doi = 10.1074/jbc.M304059200 | s2cid = 6081066 | doi-access = free}}
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{{Commonscat}}

• {{MeshName|ABCC11+protein,+human}}
• {{UCSC gene info|ABCC11}}

{{ABC transporters}}

{{DEFAULTSORT:Abcc11}}

Category:ATP-binding cassette transporters