ALMS1

ALMS1
Identifiers
Aliases	ALMS1, ALSS, centrosome and basal body associated protein, ALMS1 centrosome and basal body associated protein
External IDs	OMIM: 606844; MGI: 1934606; HomoloGene: 49406; GeneCards: ALMS1; OMA:ALMS1 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p13.1 Start 73,385,758 bp[1] End 73,625,166 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6|6 C3 Start 85,564,513 bp[2] End 85,679,735 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in buccal mucosa cell periodontal fiber cardia renal medulla ventral tegmental area pylorus inferior ganglion of vagus nerve subthalamic nucleus nipple superior surface of tongue Top expressed in spermatid primary oocyte spermatocyte secondary oocyte tail of embryo zygote genital tubercle testicle epiblast uterus More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding alpha-actinin binding molecular function Cellular component microtubule organizing center centriole cytosol centrosome cell projection spindle pole cilium cytoskeleton cytoplasm Biological process endosomal transport G2/M transition of mitotic cell cycle regulation of stress fiber assembly ciliary basal body-plasma membrane docking regulation of G2/M transition of mitotic cell cycle regulation of centriole replication positive regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7840 236266 Ensembl ENSG00000116127 ENSMUSG00000063810 UniProt Q8TCU4 Q8K4E0 RefSeq (mRNA) NM_015120 NM_001378454 NM_145223 RefSeq (protein) NP_055935 NP_660258 Location (UCSC) Chr 2: 73.39 – 73.63 Mb Chr 6: 85.56 – 85.68 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

ALMS1 is a protein which in humans is encoded by the ALMS1 gene, which is located on chromosome 2 (region 2p13.1).^[5][6][7] This gene helps with the organization of microtubules and the formation and maintenance of cilia.^[8] Autosomal recessive variants in this gene cause Alstrom Syndrome.^[8]

Discovery

The Jackson Laboratory in Bar Harbor, Maine, USA with the University of Southampton, UK identified ALMS1 as the single gene responsible for Alström syndrome.^[9][10]

Protein Function and Structure

The ALMS1 protein is relatively large and consists of 4,169 amino acids.^[11] The function of the ALMS1 protein is largely unknown, but it is known to be located on centrosomes and the base of cilia.^[12] The location of the protein within cells suggests that it may be involved in both the function of cilia and how materials are transported.^[13] Researchers believe that the protein may be involved in body weight management, blood glucose levels, hearing, vision, the heart, kidneys, lungs, and liver.^[13]

The ALMS1 protein contains the following domains^[11]:

• Tandem repeat domain (TRD)^[14]
• Leucine-zipper motif^[11]
• 130 residues at the C-terminus (ALMS motif)^[14]

Gene

The ALMS1 gene is located on the short arm of chromosome 2 (2p13.2) on the plus (Watson) strand. It is 224,161 bases in length organized into 23 exons. The encoded protein has 4,167 amino acids and molecular weight of 460,937 Da. Three isoforms are known. Mutations associated with disease are usually found in exons 8, 10 and 16.^[7]

Tissue and subcellular distribution

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.

Disease association

Variants in the ALMS1 gene have been found to be causative for Alström syndrome with a total of 268 disease-causing mutations as of 2020.^[7] These include both nonsense and frameshift mutations (insertions and deletions) that can create nonfunctional proteins.^[7] Most of the mutations have been found in exons 8,10 and 16.^[7]

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.^[15]

Organ systems

Primary cilia are hair-like projections that are on the surface of many cell types. ALMS1 is localized to the basal body of cilia and will help regulate signaling pathways all over the body.^[7] When there is a mutation in the ALMS1, the primary cilia will become dysfunctional. This will affect many pathways in the body due to this mutation. The Endocrine system is affected by a mutation in ALMS1 by having symptoms of early-onset obesity, insulin resistance, and type 2 diabetes.^[16] When looking at the cardiovascular system there is a symptom of dilated cardiomyopathy, which can lead to heart failure. In the sensory system, there is a disease called cone-rod dystrophy that takes place because of ALMS1 which can cause loss of hearing and vision. With the renal system, the mutation can cause progressive kidney dysfunction which can lead to end-stage renal disease. Lastly, the hepatic system can be affected by fatty liver disease.^[16] The mutation will cause different kinds of reactions in the organ systems.

Kidney damage

ALMS1 has a very critical role in maintaining renal function and blood pressure homeostasis. It is hypothesized that a mutation in ALMS1 in macula densa cells will amplify tubuloglomerular feedback (TGF) and cause some problems in the kidneys due to an overreaction to sodium changes.^[17] The TGF mechanism will then reduce the glomerular filtration rate (GFR). This can lead to hypertension and progressive kidney damage. All tests were done on ALMS1 knockout rats, and the outcome was higher glomerular capillary pressure and increased arterial blood pressure. Blood flow dynamics were also affected by these changes.^[18]

References

1. GRCh38: Ensembl release 89: ENSG00000116127 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000063810 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Collin GB, Marshall JD, Cardon LR, Nishina PM (February 1997). "Homozygosity mapping of Alström syndrome to chromosome 2p". Human Molecular Genetics. 6 (2): 213–219. doi:10.1093/hmg/6.2.213. PMID 9063741.
6. Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, et al. (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 Research. 4 (2): 141–150. doi:10.1093/dnares/4.2.141. PMID 9205841.
7. Tahani N, Maffei P, Dollfus H, Paisey R, Valverde D, Milan G, et al. (2020-09-21). "Consensus clinical management guidelines for Alström syndrome". Orphanet Journal of Rare Diseases. 15 (1): 253. doi:10.1186/s13023-020-01468-8. ISSN 1750-1172. PMC 7504843. PMID 32958032.
8. "ALMS1 ALMS1 centrosome and basal body associated protein [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-02.
9. Collin GB, Marshall JD, Cardon LR, Nishina PM (February 1997). "Homozygosity mapping of Alström syndrome to chromosome 2p". Human Molecular Genetics. 6 (2): 213–219. doi:10.1093/hmg/6.2.213. PMID 9063741.
10. Hearn T, Renforth GL, Spalluto G, Hanley NA, Piper K, Brickwood S, et al. (May 2002). "Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alström syndrome". Nature Genetics. 31 (1): 79–83. doi:10.1038/ng874. PMID 11941370.
11. Knorz VJ, Spalluto C, Lessard M, Purvis TL, Adigun FF, Collin GB, et al. (2010-11-01). "Centriolar association of ALMS1 and likely centrosomal functions of the ALMS motif-containing proteins C10orf90 and KIAA1731". Molecular Biology of the Cell. 21 (21): 3617–3629. doi:10.1091/mbc.E10-03-0246. ISSN 1939-4586. PMC 2965680. PMID 20844083.
12. Hearn T, Spalluto C, Phillips VJ, Renforth GL, Copin N, Hanley NA, et al. (May 2005). "Subcellular localization of ALMS1 supports involvement of centrosome and basal body dysfunction in the pathogenesis of obesity, insulin resistance, and type 2 diabetes". Diabetes. 54 (5): 1581–1587. doi:10.2337/diabetes.54.5.1581. ISSN 0012-1797. PMID 15855349.
13. "ALMS1 gene: MedlinePlus Genetics". medlineplus.gov. Retrieved 2025-12-02.
14. Hearn T (Jan 2019). "ALMS1 and Alström syndrome: a recessive form of metabolic, neurosensory and cardiac deficits". Journal of Molecular Medicine (Berlin, Germany). 97 (1): 1–17. doi:10.1007/s00109-018-1714-x. ISSN 1432-1440. PMC 6327082. PMID 30421101.
15. Li G, Vega R, Nelms K, Gekakis N, Goodnow C, McNamara P, et al. (January 2007). "A role for Alström syndrome protein, alms1, in kidney ciliogenesis and cellular quiescence". PLOS Genetics. 3 (1): e8. doi:10.1371/journal.pgen.0030008. PMC 1761047. PMID 17206865.
16. Munonye I, Sanu KP, Islam N, Gadaga C, Choudhury AR (November 2021). "A review of Alström syndrome: a rare monogenic ciliopathy". Intractable & Rare Diseases Research. 10 (4): 257–262. doi:10.5582/irdr.2021.01113. ISSN 2186-3644. PMC 8630466. PMID 34877237.
17. Potter DL, Liao TD, King KN, Ortiz PA, Monu SR (2023-10-01). "Role of Alström syndrome 1 in the regulation of glomerular hemodynamics". American Journal of Physiology. Renal Physiology. 325 (4): F418 – F425. doi:10.1152/ajprenal.00017.2023. ISSN 1522-1466. PMC 10639022. PMID 37560774.
18. Jaykumar AB, Caceres PS, King-Medina KN, Liao TD, Datta I, Maskey D, et al. (2018-11-02). "Role of Alström syndrome 1 in the regulation of blood pressure and renal function". JCI insight. 3 (21): e95076, 95076. doi:10.1172/jci.insight.95076. ISSN 2379-3708. PMC 6238740. PMID 30385718.

Further reading

• Collin GB, Marshall JD, Ikeda A, So WV, Russell-Eggitt I, Maffei P, et al. (May 2002). "Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alström syndrome". Nature Genetics. 31 (1): 74–78. doi:10.1038/ng867. PMID 11941369. S2CID 25710209.
• Hearn T, Renforth GL, Spalluto C, Hanley NA, Piper K, Brickwood S, et al. (May 2002). "Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alström syndrome". Nature Genetics. 31 (1): 79–83. doi:10.1038/ng874. PMID 11941370. S2CID 1840855.
• 't Hart LM, Maassen JA, Dekker JM, Heine RJ, Maassen JA (July 2003). "Lack of association between gene variants in the ALMS1 gene and Type 2 diabetes mellitus". Diabetologia. 46 (7): 1023–1024. doi:10.1007/s00125-003-1138-0. PMID 12827243.
• Tai TS, Lin SY, Sheu WH (2003). "Metabolic effects of growth hormone therapy in an Alström syndrome patient". Hormone Research. 60 (6): 297–301. doi:10.1159/000074248. PMID 14646408. S2CID 23942224.
• Hearn T, Spalluto C, Phillips VJ, Renforth GL, Copin N, Hanley NA, et al. (May 2005). "Subcellular localization of ALMS1 supports involvement of centrosome and basal body dysfunction in the pathogenesis of obesity, insulin resistance, and type 2 diabetes". Diabetes. 54 (5): 1581–1587. doi:10.2337/diabetes.54.5.1581. PMID 15855349.
• Patel S, Minton JA, Weedon MN, Frayling TM, Ricketts C, Hitman GA, et al. (June 2006). "Common variations in the ALMS1 gene do not contribute to susceptibility to type 2 diabetes in a large white UK population". Diabetologia. 49 (6): 1209–1213. doi:10.1007/s00125-006-0227-2. PMID 16601972.
• Marshall JD, Hinman EG, Collin GB, Beck S, Cerqueira R, Maffei P, et al. (November 2007). "Spectrum of ALMS1 variants and evaluation of genotype-phenotype correlations in Alström syndrome". Human Mutation. 28 (11): 1114–1123. doi:10.1002/humu.20577. PMID 17594715. S2CID 37118773.

External links

• GeneReviews/NCBI/NIH/UW entry on Alstrom syndrome
• OMIM entries on Alström syndrome
• ALMS1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.