ALMS1
| Alstrom syndrome 1 | |
|---|---|
| Identifiers | |
| Symbol | ALMS1 |
| Entrez | 7840 |
| HUGO | 428 |
| OMIM | 606844 |
| RefSeq | NM_015120 |
| UniProt | Q8TCU4 |
| Other data | |
| Locus | Chr. 2 p13.1 |
Alstrom syndrome 1 also known as ALMS1 is a protein which in humans is encoded by the ALMS1 gene.[1][2]
Molecular biology
The gene is located on the short arm of chromosome 2 (2p13.2) on the plus (Watson) strand. It is 224,161 bases in length organised into 23 exons. The encoded protein has 4,167 amino acids and molecular weight of 460,937 Da. Three isofoms are known. The protein itself has a large tandem-repeat domain comprising 34 imperfect repetitions of 47 amino acids. Mutations associated with disease are usually found in exons 8, 10 and 16.
The gene is expressed in fetal tissues including the aorta, brain, eye, kidney, liver, lung, olfactory bulb, pancreas, skeletal muscle, spleen and testis. The protein is found in the cytoplasm, centrosome, cell projections and cilium basal body. During mitosis it localizes to both spindle poles.
Function
Knockdown of Alms1 by short interfering RNA in mouse inner medullary collecting duct cells caused defective ciliogenesis. Cilia were stunted and treated cells lacked the ability to increase calcium influx in response to mechanical stimuli.[3]
Disease association
Mutations in the ALMS1 gene have been found to be causative for Alström syndrome with a total of 81 disease-causing mutations.[4]
Multiple mutations are known: the current (2007) total is 79. These include both nonsense and frameshift mutations. Most of the mutations have been found in exons 8,10 and 16.
Discovery
The Jackson Laboratory in Bar Harbor, Maine, USA with the University of Southampton, UK isolated ALMS1 as the single gene responsible for Alström syndrome.[1]
References
- 1 2 Collin GB, Marshall JD, Cardon LR, Nishina PM (February 1997). "Homozygosity mapping at Alström syndrome to chromosome 2p". Hum. Mol. Genet. 6 (2): 213–219. doi:10.1093/hmg/6.2.213. PMID 9063741.
- ↑ Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (April 1997). "Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Res. 4 (2): 141–150. doi:10.1093/dnares/4.2.141. PMID 9205841.
- ↑ Li G, Vega R, Nelms K, Gekakis N, Goodnow C, McNamara P, Wu H, Hong NA, Glynne R (January 2007). "A role for Alström syndrome protein, alms1, in kidney ciliogenesis and cellular quiescence". PLoS Genet. 3 (1): e8. doi:10.1371/journal.pgen.0030008. PMC 1761047
. PMID 17206865. - ↑ Joy T, Cao H, Black G, Malik R, Charlton-Menys V, Hegele RA, Durrington PN (2007). "Alstrom syndrome (OMIM 203800): a case report and literature review". Orphanet Journal of Rare Diseases. 2 (1): 49. doi:10.1186/1750-1172-2-49. PMC 2266715. PMID 18154657.
External links
- GeneReviews/NCBI/NIH/UW entry on Alstrom syndrome
- OMIM entries on Alström syndrome
- ALMS1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)