HGNC Approved Gene Symbol: ARSI
Cytogenetic location: 5q32 Genomic coordinates (GRCh38) : 5:150,296,343-150,302,905 (from NCBI)
Sulfatases such as arylsulfatase I (ARSI) hydrolyze sulfate esters from sulfated steroids, carbohydrates, proteoglycans, and glycolipids. They are involved in hormone biosynthesis, modulation of cell signaling, and degradation of macromolecules (Sardiello et al., 2005).
By searching databases for novel sulfatase genes, Sardiello et al. (2005) and Obaya (2006) identified ARSI. They determined that all human sulfatases, including ARSI, have 9 regions of strong evolutionary conservation, most of which contain residues involved in the sulfatase hydrolysis reaction. ARSI shares 57% amino acid identity with ARSJ (610010).
Obaya (2006) cloned full-length ARSI cDNA from a human fetal lung cDNA library. The deduced 569-amino acid protein has a predicted molecular mass of 64 kD. Northern blot analysis detected high expression of an approximately 4.4-kb transcript in fetal lung, with lower expression in fetal kidney, placenta, and a lung carcinoma cell line; no expression was found in any other normal adult tissue examined. Western blot analysis of HeLa cells expressing epitope-tagged ARSI detected the protein only in the particulate fraction, suggesting ARSI associates with cellular organelles or membrane structures.
Sardiello et al. (2005) and Obaya (2006) determined that the ARSI gene contains 2 exons. Obaya (2006) found that the ARSI gene spans about 5.2 kb.
Sardiello et al. (2005) and Obaya (2006) stated that the ARSI gene maps to chromosome 5q32.
Obaya (2006) noted that the mouse Arsi gene maps to a region of chromosome 18 that shares homology of synteny with human chromosome 5q32; the rat and chimpanzee Arsi genes also map to syntenic chromosomal regions.
For discussion of a possible association between variation in the ARSI gene and spastic paraplegia, see 610009.0001.
This variant is classified as a variant of unknown significance because its contribution to spastic paraplegia has not been confirmed.
In 2 affected members of a consanguineous family (family 1349) segregating spastic paraplegia, Novarino et al. (2014) identified a 1-bp insertion (1641insA) in the ARSI gene, resulting in a frameshift and premature termination (Cys548Metfs559Ter). The phenotype was reported for only 1 patient, a girl who presented at 1.5 years of age with abnormal gait, absent deep tendon reflexes, pes equinovarus, and a brain MRI showing corpus callosum and cerebellar hypoplasia with colpocephaly. She also had severe sensory motor and polyneuropathy as well as borderline IQ at 3.5 years of age. Novarino et al. (2014) labeled the disorder spastic paraplegia-66 (SPG66).
Novarino, G., Fenstermaker, A. G., Zaki, M. S., Hofree, M., Silhavy, J. L., Heiberg, A. D., Abdellateef, M., Rosti, B., Scott, E., Mansour, L., Masri, A., Kayserili, H., and 41 others. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science 343: 506-511, 2014. [PubMed: 24482476] [Full Text: https://doi.org/10.1126/science.1247363]
Obaya, A. J. Molecular cloning and initial characterization of three novel human sulfatases. Gene 372: 110-117, 2006. [PubMed: 16500042] [Full Text: https://doi.org/10.1016/j.gene.2005.12.023]
Sardiello, M., Annunziata, I., Roma, G., Ballabio, A. Sulfatases and sulfatase modifying factors: an exclusive and promiscuous relationship. Hum. Molec. Genet. 14: 3203-3217, 2005. [PubMed: 16174644] [Full Text: https://doi.org/10.1093/hmg/ddi351]