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MCOLN1 gene

mucolipin 1
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Normal Function

The MCOLN1 gene provides instructions for making a protein called mucolipin-1. This protein is located in the membranes of lysosomes and endosomes, compartments within the cell that digest and recycle materials. While its function is not completely understood, mucolipin-1 plays a role in the transport (trafficking) of fats (lipids) and proteins between lysosomes and endosomes.

Mucolipin-1 acts as a channel, allowing positively charged atoms (cations) to cross the membranes of lysosomes and endosomes. It remains unclear which cations are allowed to flow through this channel. Mucolipin-1 appears to be important for the development and maintenance of the brain and light-sensitive tissue at the back of the eye (retina). In addition, this protein is likely critical for normal functioning of the cells in the stomach that produce digestive acids.

Health Conditions Related to Genetic Changes

Mucolipidosis type IV

At least 22 mutations in the MCOLN1 gene have been found to cause mucolipidosis type IV. Most of these mutations result in the production of a nonfunctional protein or prevent any protein from being produced. Two mutations in the MCOLN1 gene account for almost all cases of mucolipidosis type IV in people with Ashkenazi Jewish ancestry. The most common mutation, written as 406-2A>G, changes a single DNA building block (nucleotide) in a region of the gene known as intron 3. This mutation, which is called a splice-site mutation, introduces a premature stop signal in the instructions for making mucolipin-1. The other mutation, written as 511_6943del, deletes a large amount of DNA near the beginning of the MCOLN1 gene. Both of these mutations result in the production of an abnormally short, nonfunctional protein.

A lack of functional mucolipin-1 impairs transport of lipids and proteins, causing these substances to build up inside lysosomes. It remains unclear how mutations in the MCOLN1 gene lead to delayed development of mental and motor skills (psychomotor delay), progressive vision loss, and impaired secretion of stomach acid (achlorhydia) in people with mucolipidosis type IV.

More About This Health Condition

Other Names for This Gene

  • MCLN1_HUMAN
  • ML4
  • MLIV
  • MST080
  • MSTP080
  • mucolipidin
  • TRP-ML1
  • TRPML1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

References

  • Dong XP, Cheng X, Mills E, Delling M, Wang F, Kurz T, Xu H. The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel. Nature. 2008 Oct 16;455(7215):992-6. doi: 10.1038/nature07311. Epub 2008 Sep 14. Citation on PubMed or Free article on PubMed Central
  • Miedel MT, Rbaibi Y, Guerriero CJ, Colletti G, Weixel KM, Weisz OA, Kiselyov K. Membrane traffic and turnover in TRP-ML1-deficient cells: a revised model for mucolipidosis type IV pathogenesis. J Exp Med. 2008 Jun 9;205(6):1477-90. doi: 10.1084/jem.20072194. Epub 2008 May 26. Citation on PubMed or Free article on PubMed Central
  • Puertollano R, Kiselyov K. TRPMLs: in sickness and in health. Am J Physiol Renal Physiol. 2009 Jun;296(6):F1245-54. doi: 10.1152/ajprenal.90522.2008. Epub 2009 Jan 21. Review. Citation on PubMed or Free article on PubMed Central
  • Ruivo R, Anne C, SagnĂ© C, Gasnier B. Molecular and cellular basis of lysosomal transmembrane protein dysfunction. Biochim Biophys Acta. 2009 Apr;1793(4):636-49. doi: 10.1016/j.bbamcr.2008.12.008. Epub 2008 Dec 24. Review. Citation on PubMed
  • Schiffmann R, Grishchuk Y, Goldin E. Mucolipidosis IV. 2005 Jan 28 [updated 2015 Jul 30]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from http://www.ncbi.nlm.nih.gov/books/NBK1214/ Citation on PubMed
  • Venugopal B, Mesires NT, Kennedy JC, Curcio-Morelli C, Laplante JM, Dice JF, Slaugenhaupt SA. Chaperone-mediated autophagy is defective in mucolipidosis type IV. J Cell Physiol. 2009 May;219(2):344-53. doi: 10.1002/jcp.21676. Citation on PubMed
  • Vergarajauregui S, Connelly PS, Daniels MP, Puertollano R. Autophagic dysfunction in mucolipidosis type IV patients. Hum Mol Genet. 2008 Sep 1;17(17):2723-37. doi: 10.1093/hmg/ddn174. Epub 2008 Jun 11. Citation on PubMed or Free article on PubMed Central
  • Vergarajauregui S, Oberdick R, Kiselyov K, Puertollano R. Mucolipin 1 channel activity is regulated by protein kinase A-mediated phosphorylation. Biochem J. 2008 Mar 1;410(2):417-25. Citation on PubMed
  • Vergarajauregui S, Puertollano R. Mucolipidosis type IV: the importance of functional lysosomes for efficient autophagy. Autophagy. 2008 Aug;4(6):832-4. Epub 2008 Jul 8. Citation on PubMed or Free article on PubMed Central
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