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ABCC11

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ABCC11
Identifiers
AliasesABCC11, ATP-binding cassette, sub-family C (CFTR/MRP), member 11, EWWD, MRP8, WW, ATP binding cassette subfamily C member 11, ATP-binding cassette transporter sub-family C member 1
External IDsOMIM: 607040; HomoloGene: 69511; GeneCards: ABCC11; OMA:ABCC11 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

85320

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Ensembl

ENSG00000121270

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UniProt

Q96J66

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RefSeq (mRNA)

NM_032583
NM_033151
NM_145186
NM_001370496
NM_001370497

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RefSeq (protein)

n/a

Location (UCSC)Chr 16: 48.17 – 48.25 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

ATP-binding cassette transporter sub-family C member 11, also MRP8 (Multidrug Resistance-Related Protein 8), is a membrane transporter that exports certain molecules from inside a cell. It is a protein that in humans is encoded by gene ABCC11.[3][4][5]

The gene is responsible for determination of human cerumen type (wet or dry ear wax) and presence of underarm osmidrosis (odor associated with sweat caused by apocrine secretion), and is associated with colostrum secretion.[6]

Function

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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.[5]

Molecular genetics

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Location of ABCC11 with its 30 exons on chromosome 16. The important single nucleotide polymorphism (SNP) 538G → A is located on exon 4.

The ABCC11 gene is present in the human genome as two alleles, differing in one nucleotide also known as a single nucleotide polymorphism (SNP).[7] 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.[7][8] 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.[9][10] The GG or GA genotype produces the wet ear wax phenotype (sticky and brown colored) and acrid sweat odor and is the dominant allele.[9] 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.[9]

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.[7] This effect is localized to ceruminous gland membranes.[7] 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.[7]

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.[8] In some nonhuman mammals, mating signals via release of an odor enhanced by increased apocrine secretion may be a factor in sexual selection.[8]

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.

Demographics

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World map of the distribution of the A allele of the single nucleotide polymorphism rs17822931 in the ABCC11 gene. The proportion of A alleles in each population is represented by the white area in each circle.

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.[8] It is believed that the derived allele originated in an ancient East Asian population.[11] 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.[12]

An analysis of ancient DNA of Eastern European hunter gatherers, Scandinavian Hunter Gatherers, Western Hunter Gatherers and Early European Farmers. The study 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.[13]

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.[8] The derived allele is not rare in South Asia, with 54% of Dravidian people from Tamil Nadu carrying an AA genotype.[8] 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.[8] 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.[8][14]

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.[15]

See also

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References

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Citations

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000121270 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ Tammur J, Prades C, Arnould I, Rzhetsky A, Hutchinson A, Adachi M, et al. (Jul 2001). "Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12". Gene. 273 (1): 89–96. doi:10.1016/S0378-1119(01)00572-8. PMID 11483364.
  4. ^ Dean M, Rzhetsky A, Allikmets R (Jul 2001). "The human ATP-binding cassette (ABC) transporter superfamily". Genome Research. 11 (7): 1156–66. doi:10.1101/gr.184901. PMID 11435397. S2CID 9528197.
  5. ^ a b "Entrez Gene: ABCC11 ATP-binding cassette, sub-family C (CFTR/MRP), member 11".
  6. ^ Miura K, Yoshiura Ki, Miura S, Shimada T, Yamasaki K, Yoshida A, et al. (June 2007). "A strong association between human earwax-type and apocrine colostrum secretion from the mammary gland". Human Genetics. 121 (5): 631–633. doi:10.1007/s00439-007-0356-9. ISSN 0340-6717. PMID 17394018. S2CID 575882.
  7. ^ a b c d e Toyoda Y, Sakurai A, Mitani Y, Nakashima M, Yoshiura K, Nakagawa H, et al. (Jun 2009). "Earwax, osmidrosis, and breast cancer: why does one SNP (538G>A) in the human ABC transporter ABCC11 gene determine earwax type?". FASEB Journal. 23 (6): 2001–13. doi:10.1096/fj.09-129098. PMID 19383836. S2CID 26853548.
  8. ^ a b c d e f g h Yoshiura K, Kinoshita A, Ishida T, Ninokata A, Ishikawa T, Kaname T, et al. (Mar 2006). "A SNP in the ABCC11 gene is the determinant of human earwax type". Nature Genetics. 38 (3): 324–30. doi:10.1038/ng1733. PMID 16444273. S2CID 3201966.
  9. ^ a b c Rodriguez S, Steer CD, Farrow A, Golding J, Day IN (Jul 2013). "Dependence of deodorant usage on ABCC11 genotype: scope for personalized genetics in personal hygiene". The Journal of Investigative Dermatology. 133 (7): 1760–7. doi:10.1038/jid.2012.480. PMC 3674910. PMID 23325016.
  10. ^ Park YJ, Shin MS (Sep 2001). "What is the best method for treating osmidrosis?". Annals of Plastic Surgery. 47 (3): 303–9. doi:10.1097/00000637-200109000-00014. PMID 11562036. S2CID 25590802.
  11. ^ Hori YS, Yamada A, Matsuda N, Ono Y, Starenki D, Sosonkina N, et al. (2017). "A Novel Association between the 27-bp Deletion and 538G>A Mutation in the ABCC11 Gene". Human Biology. 89 (4): 305–307. doi:10.13110/humanbiology.89.4.04. ISSN 1534-6617. PMID 30047321. S2CID 51721105. "were highest in East Asia, with decreasing frequencies observed toward Europe and Southern Asia, suggesting an East Asian origin."
  12. ^ Martin A, Saathoff M, Kuhn F, Max H, Terstegen L, Natsch A (February 2010). "A functional ABCC11 allele is essential in the biochemical formation of human axillary odor". The Journal of Investigative Dermatology. 130 (2): 529–540. doi:10.1038/jid.2009.254. PMID 19710689. S2CID 36754463.
  13. ^ Günther T, Malmström H, Svensson EM (January 2018). "Population genomics of Mesolithic Scandinavia: Investigating early postglacial migration routes and high-latitude adaptation". PLOS Biology. 16 (1): e2003703. doi:10.1371/journal.pbio.2003703. PMC 5760011. PMID 29315301. From 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: Supporting Information File S1
  14. ^ Prokop-Prigge KA, Mansfield CJ, Parker MR, Thaler E, Grice EA, Wysocki CJ, et al. (Jan 2015). "Ethnic/racial and genetic influences on cerumen odorant profiles". Journal of Chemical Ecology. 41 (1): 67–74. Bibcode:2015JCEco..41...67P. doi:10.1007/s10886-014-0533-y. PMC 4304888. PMID 25501636.
  15. ^ Prokop-Prigge KA, Greene K, Varallo L, Wysocki CJ, Preti G (2016). "The Effect of Ethnicity on Human Axillary Odorant Production". Journal of Chemical Ecology. 42 (1): 33–9. Bibcode:2016JCEco..42...33P. doi:10.1007/s10886-015-0657-8. PMC 4724538. PMID 26634572.

Sources

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Further reading

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