{{Short description|Gene on human chromosome 16, implicated in neuropathy}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox gene}} '''Alanyl—tRNA synthetase 1''' (AARS1) is an enzyme that is encoded by the AARS1 gene in humans and is a member of the aminoacyl-tRNA synthetases (ARSs) family of enzymes.<ref>{{Cite web |title=AARS1 alanyl-tRNA synthetase 1 [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene/16 |access-date=2024-11-25 |website=www.ncbi.nlm.nih.gov}}</ref>
==Clinical significance==
=== Charcot-Marie-Tooth Disease === Charcot-Marie-Tooth Disease type 2 (CMT2) and other peripheral neuropathies have been linked to mutations in the '''AARS1''', GARS1, HARS1, WARS1, and YARS1 genes.<ref>{{cite journal | vauthors = Høyer H, Busk ØL, Esbensen QY, Røsby O, Hilmarsen HT, Russell MB, Nyman TA, Braathen GJ, Nilsen HL | title = Clinical characteristics and proteome modifications in two Charcot-Marie-Tooth families with the AARS1 Arg326Trp mutation | journal = BMC Neurology | volume = 22 | issue = 1 | pages = 299 | date = August 2022 | pmid = 35971119 | pmc = 9377087 | doi = 10.1186/s12883-022-02828-6 | doi-access = free }}</ref> Mutations in these genes can encode for faulty aminoacyl-tRNA synthetases, which affects a highly conserved amino acid in the helical domain of cytoplasmic AARS1.<ref>{{cite journal | vauthors = Latour P, Thauvin-Robinet C, Baudelet-Méry C, Soichot P, Cusin V, Faivre L, Locatelli MC, Mayençon M, Sarcey A, Broussolle E, Camu W, David A, Rousson R | title = A major determinant for binding and aminoacylation of tRNA(Ala) in cytoplasmic Alanyl-tRNA synthetase is mutated in dominant axonal Charcot-Marie-Tooth disease | journal = American Journal of Human Genetics | volume = 86 | issue = 1 | pages = 77–82 | date = January 2010 | pmid = 20045102 | pmc = 2801750 | doi = 10.1016/j.ajhg.2009.12.005 }}</ref> This disrupts the ability to charge tRNA with its corresponding amino acids, which leads to impaired protein synthesis. In AARS1, mutations are associated with both autosomal dominant and recessive forms of CMT2.<ref>{{cite journal | vauthors = Nam DE, Park JH, Park CE, Jung NY, Nam SH, Kwon HM, Kim HS, Kim SB, Son WS, Choi BO, Chung KW | title = Variants of aminoacyl-tRNA synthetase genes in Charcot-Marie-Tooth disease: A Korean cohort study | journal = Journal of the Peripheral Nervous System | volume = 27 | issue = 1 | pages = 38–49 | date = March 2022 | pmid = 34813128 | doi = 10.1111/jns.12476 }}</ref>
=== Trichothiodystrophy === In addition to its role in CMT2, mutations in the AARS1 gene have also been implicated in non-photosensitive trichothiodystrophy (NPS-TTD),<ref name="Botta_2021">{{cite journal | vauthors = Botta E, Theil AF, Raams A, Caligiuri G, Giachetti S, Bione S, Accadia M, Lombardi A, Smith DE, Mendes MI, Swagemakers SM, van der Spek PJ, Salomons GS, Hoeijmakers JH, Yesodharan D, Nampoothiri S, Ogi T, Lehmann AR, Orioli D, Vermeulen W | title = Protein instability associated with AARS1 and MARS1 mutations causes trichothiodystrophy | journal = Human Molecular Genetics | volume = 30 | issue = 18 | pages = 1711–1720 | date = August 2021 | pmid = 33909043 | pmc = 8411986 | doi = 10.1093/hmg/ddab123 }}</ref> a rare hereditary neurodevelopmental disorder. Trichothiodystrophy (TTD) is defined by sulfur-deficient brittle hair, nails, and scaly skin,<ref name="Botta_2021" /> but presents with variable clinical features. Unlike the photosensitive form of TTD (PS-TTD), which exhibits features of progressive neuropathy and accelerated aging, NPS-TTD is not associated with premature aging.<ref name="Botta_2021" />
Research has identified AARS1, along with methionyl-tRNA synthetase 1 as genes in which variants can contribute to the development NPS-TTD.<ref name="Botta_2021" /> These variants lead to the instability of the respective enzymes which they encode, affecting the rate of tRNA charging,<ref name="Botta_2021" /> which is the first step in protein translation.
== References == {{reflist}}
Category:Genes on human chromosome 16