Gene Symbol: Mcoln3
Description: mucolipin 3
Alias: 6720490O21Rik, TRPML3, mucolipin-3, transient receptor potential channel mucolipin 3, varitint-waddler
Species: mouse
Products:     Mcoln3

Top Publications

  1. Xu H, Delling M, Li L, Dong X, Clapham D. Activating mutation in a mucolipin transient receptor potential channel leads to melanocyte loss in varitint-waddler mice. Proc Natl Acad Sci U S A. 2007;104:18321-6 pubmed
    ..A mutation in mouse TRPML3 (A419P; TRPML3(Va)) results in the varitint-waddler (Va) phenotype...
  2. Venkatachalam K, Hofmann T, Montell C. Lysosomal localization of TRPML3 depends on TRPML2 and the mucolipidosis-associated protein TRPML1. J Biol Chem. 2006;281:17517-27 pubmed
    ..Mammals encode two additional TRPML proteins named TRPML2 and TRPML3. Information regarding the propensity of these proteins to multimerize, their subcellular distribution and ..
  3. Di Palma F, Belyantseva I, Kim H, Vogt T, Kachar B, Noben Trauth K. Mutations in Mcoln3 associated with deafness and pigmentation defects in varitint-waddler (Va) mice. Proc Natl Acad Sci U S A. 2002;99:14994-9 pubmed
    ..using a positional cloning strategy, we identify two additional members of the mucolipin gene family (Mcoln2 and Mcoln3) in the 350-kb Va(J) minimal interval and provide evidence for Mcoln3 as the gene mutated in varitint-waddler...
  4. Grimm C, Jörs S, Heller S. Life and death of sensory hair cells expressing constitutively active TRPML3. J Biol Chem. 2009;284:13823-31 pubmed publisher
    The varitint-waddler mutation A419P renders TRPML3 constitutively active, resulting in cationic overload, particularly in sustained influx of Ca(2+)...
  5. Grimm C, Cuajungco M, van Aken A, Schnee M, Jörs S, Kros C, et al. A helix-breaking mutation in TRPML3 leads to constitutive activity underlying deafness in the varitint-waddler mouse. Proc Natl Acad Sci U S A. 2007;104:19583-8 pubmed
    Homozygote varitint-waddler (Va) mice, expressing a mutant isoform (A419P) of TRPML3 (mucolipin 3), are profoundly deaf and display vestibular and pigmentation deficiencies, sterility, and perinatal lethality...
  6. Lelouvier B, Puertollano R. Mucolipin-3 regulates luminal calcium, acidification, and membrane fusion in the endosomal pathway. J Biol Chem. 2011;286:9826-32 pubmed publisher
    Mucolipin-3 (MCOLN3) is a pH-regulated Ca(2+) channel that localizes to the endosomal pathway...
  7. Kim H, Jackson T, Noben Trauth K. Genetic analyses of the mouse deafness mutations varitint-waddler (Va) and jerker (Espnje). J Assoc Res Otolaryngol. 2003;4:83-90 pubmed
    ..The results establish the framework for cloning the Va gene and provide valuable insights into the genetics of deafness mutations in the mouse. ..
  8. Cable J, Steel K. Combined cochleo-saccular and neuroepithelial abnormalities in the Varitint-waddler-J (VaJ) mouse. Hear Res. 1998;123:125-36 pubmed
  9. Nagata K, Zheng L, Madathany T, Castiglioni A, Bartles J, Garcia Anoveros J. The varitint-waddler (Va) deafness mutation in TRPML3 generates constitutive, inward rectifying currents and causes cell degeneration. Proc Natl Acad Sci U S A. 2008;105:353-8 pubmed
    ..Va mutation results in an alanine-to-proline substitution at residue 419 (A419P) of the presumed ion channel TRPML3. Another allele, Va(J), has the A419P mutation in addition to an I362T mutation...

More Information


  1. Castiglioni A, REMIS N, Flores E, Garcia Anoveros J. Expression and vesicular localization of mouse Trpml3 in stria vascularis, hair cells, and vomeronasal and olfactory receptor neurons. J Comp Neurol. 2011;519:1095-1114 pubmed publisher
    ..A dominant missense mutation in Trpml3 (also known as Mcoln3) causes deafness and vestibular impairment characterized by stereocilia disorganization, hair cell loss, and ..
  2. Kim H, Li Q, Tjon Kon Sang S, So I, Kiselyov K, Muallem S. Gain-of-function mutation in TRPML3 causes the mouse Varitint-Waddler phenotype. J Biol Chem. 2007;282:36138-42 pubmed
    b>TRPML3 is a member of the TRPML subfamily of the transient receptor potential cation channel superfamily...
  3. van Aken A, Atiba Davies M, Marcotti W, Goodyear R, Bryant J, Richardson G, et al. TRPML3 mutations cause impaired mechano-electrical transduction and depolarization by an inward-rectifier cation current in auditory hair cells of varitint-waddler mice. J Physiol. 2008;586:5403-18 pubmed publisher
    b>TRPML3 (mucolipin-3) belongs to one of the transient-receptor-potential (TRP) ion channel families...
  4. Prochazka M, Staeheli P, Holmes R, Haller O. Interferon-induced guanylate-binding proteins: mapping of the murine Gbp-1 locus to chromosome 3. Virology. 1985;145:273-9 pubmed
  5. Lane P. Two new mutations in linkage group XVI of the house mouse. Flaky tail and varitint-waddler-J. J Hered. 1972;63:135-40 pubmed
  6. REMIS N, Wiwatpanit T, Castiglioni A, Flores E, Cantú J, García Añoveros J. Mucolipin co-deficiency causes accelerated endolysosomal vacuolation of enterocytes and failure-to-thrive from birth to weaning. PLoS Genet. 2014;10:e1004833 pubmed publisher
    ..before weaning express high levels of two endolysosomal cation channels, mucolipins 3 and 1 -products of Trpml3 and Trpml1 genes; moreover neonatal enterocytes of mice lacking both mucolipins (Trpml3-/-;Trpml1-/-) vacuolated ..
  7. Goswami C, Hucho T. Submembraneous microtubule cytoskeleton: biochemical and functional interplay of TRP channels with the cytoskeleton. FEBS J. 2008;275:4684-99 pubmed publisher
    ..Thereby, we point out the functional importance of cytoskeleton components both as modulator and as modulated downstream effector. The resulting implications for patho-biological situations are discussed. ..
  8. Mobraaten L, Bunker H, DeMaeyer Guignard J, Demaeyer E, Bailey D. Location of histocompatibility and interferon loci on chromosome 3 of the mouse. J Hered. 1984;75:233-4 pubmed
    ..The gene order (from centromere) with intervening percent recombination is: ma-19.1(+/- 4.9)-H-23-12.0(+/- 4.0)-VaJ-7.7(+/- 2.2)-H-28-5.9(+/- 2.2)-If-1. ..
  9. Staaf S, Oerther S, Lucas G, Mattsson J, Ernfors P. Differential regulation of TRP channels in a rat model of neuropathic pain. Pain. 2009;144:187-99 pubmed publisher
    ..Of all TRP channel members, TRPML3 showed the most dramatic change in animals exhibiting neuropathic pain behaviour compared to control animals...
  10. Cuajungco M, Samie M. The varitint-waddler mouse phenotypes and the TRPML3 ion channel mutation: cause and consequence. Pflugers Arch. 2008;457:463-73 pubmed publisher
    ..Positional cloning approach has identified two mutations in the TRPML3 (Mcoln3) gene that cause the varitint-waddler mouse phenotypes...
  11. Jörs S, Grimm C, Becker L, Heller S. Genetic inactivation of Trpml3 does not lead to hearing and vestibular impairment in mice. PLoS ONE. 2010;5:e14317 pubmed publisher
    b>TRPML3, a member of the transient receptor potential (TRP) family, is an inwardly rectifying, non-selective Ca2+-permeable cation channel that is regulated by extracytosolic Na+ and H+ and can be activated by a variety of small molecules...
  12. Van Buul P, Tuinenburg Bol Raap A, Goudzwaard H, Seelen C, Beechey C, Natarajan A, et al. Cytogenetic characterization of radiosensitive mouse mutants. Mutat Res. 1991;251:171-9 pubmed
    ..Only Va and dt appear to be associated with some deficiency in DNA repair. ..
  13. Miao Y, Li G, Zhang X, Xu H, Abraham S. A TRP Channel Senses Lysosome Neutralization by Pathogens to Trigger Their Expulsion. Cell. 2015;161:1306-19 pubmed publisher
    ..This change is detected by mucolipin TRP channel 3 (TRPML3), a transient receptor potential cation channel localized to lysosomes...
  14. Eicher E, Lane P. Assignment of LH XVI to chromosome 3 in the mouse. J Hered. 1980;71:315-8 pubmed
    ..The genetic location of the breakpoint in the reciprocal translocation T(2:3)24H is placed between the Amy-1 and Va loci. A new simplified method for determining the Amy-1 and Amy-2 genotype of mice is presented. ..
  15. Lane P, Eicher E. Gene order in linkage group XVI of the house mouse. J Hered. 1979;70:239-44 pubmed
    ..We conclude that LG XVI is not carried on Chr 12, and preliminary data indicates it is most likely carried on Chr 3. ..
  16. CURRY G. Genetical and development studies on droopy-eared mice. J Embryol Exp Morphol. 1959;7:39-65 pubmed
  17. Holmes R, Albanese R, Whitehead F, Duley J. Mouse alcohol dehydrogenase isozymes: products of closely localized duplicate genes exhibiting divergent kinetic properties. J Exp Zool. 1981;217:151-7 pubmed
  18. Kocher W. [Studies on the genetics and pathology of the development of 8 labyrinth mutants (deaf-waltzer-shaker mutants) in the mouse (Mus musculus)]. Z Vererbungsl. 1960;91:114-40 pubmed
  19. Lane P, Bronson R, Spencer C. Rostral cerebellar malformation, (rcm): a new recessive mutation on chromosome 3 of the mouse. J Hered. 1992;83:315-8 pubmed
    ..The mutation, called rostral cerebellar malformation, rcm, has been located on chromosome (Chr) 3 between the alcohol dehydrogenase-3 (Adh-3) complex and varitint waddler-J (VaJ).
  20. Steele E, Lyon M, Favor J, Guillot P, Boyd Y, Church R. A mutation in the connexin 50 (Cx50) gene is a candidate for the No2 mouse cataract. Curr Eye Res. 1998;17:883-9 pubmed
    ..The aim of this work was to identify and subsequently screen an optimal candidate gene for a mutation correlated and consistent with the observed phenotype...
  21. Cools A. Asymmetrical spotting and direction of circling in the varitint-waddler mouse. J Hered. 1972;63:167-71 pubmed
  22. Taylor B. Linkage of the cadmium resistance locus to loci on mouse chromosome 12. J Hered. 1976;67:389-90 pubmed
    ..A 3-point cross involving Va, cdm, and amylase-1 (Amy-1) indicated the following gene order and approximate distances: Va-8-cdm-17-Amy-1. The cdm locus is the first polymorphic locus to be placed on Chromosome 12. ..
  23. Cabraja M, Bäurle J. Vestibular ganglion neurons survive hair cell defects in jerker, shaker, and Varitint-waddler mutants and downregulate calretinin expression. J Comp Neurol. 2007;504:418-26 pubmed
    ..Whether the decrease in Calr expression may reflect biochemical adaptations in response to input disturbances or a specific loss of large BNs is discussed. ..
  24. Atiba Davies M, Noben Trauth K. TRPML3 and hearing loss in the varitint-waddler mouse. Biochim Biophys Acta. 2007;1772:1028-31 pubmed
    TRPML3 (also known as mucolipin-3, MCOLN3) belongs to the small family of TRPML ion channel proteins...
  25. Calderon A, Derr A, Stagner B, Johnson K, Martin G, Noben Trauth K. Cochlear developmental defect and background-dependent hearing thresholds in the Jackson circler (jc) mutant mouse. Hear Res. 2006;221:44-58 pubmed
    ..Genome-wide linkage scans of backcross, intercross, and congenic progeny revealed a complex pattern of genetic and stochastic effects. ..
  26. Duley J, Holmes R. Biochemical genetics of aldehyde reductase in the mouse: Ahr-1--a new locus linked to the alcohol dehydrogenase gene complex on chromosome 3. Biochem Genet. 1982;20:1067-83 pubmed
    ..It is proposed that Ahr-1 is a product of a gene duplication event during mammalian evolution of the primordial mammalian Adh locus and that considerable divergence in catalytic properties has subsequently occurred. ..
  27. Marks S, Lane P. Osteopetrosis, a new recessive skeletal mutation on chromosome 12 of the mouse. J Hered. 1976;67:11-18 pubmed
  28. Holmes R. Genetics and ontogeny of alcohol dehydrogenase isozymes in the mouse: evidence for a cis-acting regulator gene (Adt-i) controlling C2 isozyme expression in reproductive tissues and close linkage of Adh-3 and Adt-i on chromosome 3. Biochem Genet. 1979;17:461-72 pubmed