Encyclopedia
mucolipin 1
- genes
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 ConditionOther Names for This Gene
- MCLN1_HUMAN
- ML4
- MLIV
- MST080
- MSTP080
- mucolipidin
- TRP-ML1
- TRPML1
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/mcoln1
References
- Dong XP, Cheng X, Mills E, Delling M, Wang F, Kurz T, Xu H. The type IVmucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel.Nature. 2008 Oct 16;455(7215):992-6. doi: 10.1038/nature07311.
- Miedel MT, Rbaibi Y, Guerriero CJ, Colletti G, Weixel KM, Weisz OA, KiselyovK. 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.
- Puertollano R, Kiselyov K. TRPMLs: in sickness and in health. Am J PhysiolRenal Physiol. 2009 Jun;296(6):F1245-54. doi: 10.1152/ajprenal.90522.2008.
- Ruivo R, Anne C, Sagné C, Gasnier B. Molecular and cellular basis of lysosomaltransmembrane protein dysfunction. Biochim Biophys Acta. 2009 Apr;1793(4):636-49.doi: 10.1016/j.bbamcr.2008.12.008.
- Schiffmann R, Grishchuk Y, Goldin E. Mucolipidosis IV. 2005 Jan 28 [updated2015 Jul 30]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University ofWashington, Seattle; 1993-2020. Available fromhttp://www.ncbi.nlm.nih.gov/books/NBK1214/
- 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.
- Vergarajauregui S, Connelly PS, Daniels MP, Puertollano R. Autophagicdysfunction in mucolipidosis type IV patients. Hum Mol Genet. 2008 Sep1;17(17):2723-37. doi: 10.1093/hmg/ddn174.
- 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.
- Vergarajauregui S, Puertollano R. Mucolipidosis type IV: the importance offunctional lysosomes for efficient autophagy. Autophagy. 2008 Aug;4(6):832-4.
