# ASAH1

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Protein-coding gene in the species Homo sapiens

ASAH1 Identifiers Aliases ASAH1, AC, ACDase, ASAH, PHP, PHP32, SMAPME, N-acylsphingosine amidohydrolase (acid ceramidase) 1, N-acylsphingosine amidohydrolase 1 External IDs OMIM: 613468; MGI: 1277124; HomoloGene: 10504; GeneCards: ASAH1; OMA:ASAH1 - orthologs Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8p22 Start 18,055,992 bp[1] End 18,084,998 bp[1] Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 A4 Start 41,793,234 bp[2] End 41,827,810 bp[2] RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right ventricle visceral pleura pancreatic ductal cell retinal pigment epithelium myocardium parietal pleura nasal epithelium monocyte renal medulla left ventricle Top expressed in saccule stroma of bone marrow endothelial cell of lymphatic vessel otic placode iris calvaria ciliary body parotid gland Epithelium of choroid plexus epithelium of stomach More reference expression data BioGPS More reference expression data Gene ontology Molecular function N-acylsphingosine amidohydrolase activity catalytic activity hydrolase activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds ceramidase activity hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides Cellular component lysosome lysosomal lumen extracellular exosome extracellular region extracellular space tertiary granule lumen ficolin-1-rich granule lumen early endosome endoplasmic reticulum nucleus cytoplasm Biological process glycosphingolipid metabolic process ceramide metabolic process lipid metabolism neutrophil degranulation sphingosine biosynthetic process ceramide biosynthetic process ceramide catabolic process keratinocyte differentiation regulation of steroid biosynthetic process regulation of programmed necrotic cell death cellular response to tumor necrosis factor sphingolipid metabolic process Sources:Amigo / QuickGO Orthologs Species Human Mouse Entrez 427 11886 Ensembl ENSG00000104763 ENSMUSG00000031591 UniProt Q13510 Q9WV54 RefSeq (mRNA) NM_001127505 NM_004315 NM_177924 NM_001363743 NM_019734 RefSeq (protein) NP_001120977 NP_004306 NP_808592 NP_001350672 NP_062708 Location (UCSC) Chr 8: 18.06 – 18.08 Mb Chr 8: 41.79 – 41.83 Mb PubMed search [3] [4] Wikidata View/Edit Human View/Edit Mouse

The **ASAH1** [gene](/source/Gene) encodes in humans the *acid [ceramidase](/source/Ceramidase)* [enzyme](/source/Enzyme).[5][6][7]

## Function

This gene encodes a [heterodimeric](/source/Heterodimeric#Biochemistry) protein consisting of a nonglycosylated alpha subunit and a [glycosylated](/source/Glycosylation) beta subunit that is cleaved to the mature enzyme [posttranslationally](/source/Posttranslational_modification). The encoded protein catalyzes the synthesis and degradation of [ceramide](/source/Ceramide) into [sphingosine](/source/Sphingosine) and fatty acid. Mutations in this gene have been associated with a [lysosomal storage disorder](/source/Lysosomal_storage_disorder) known as [Farber disease](/source/Farber_disease) and, recently, with a rare neurodegenerative condition known as [spinal muscular atrophy with progressive myoclonic epilepsy](/source/Spinal_muscular_atrophy_with_progressive_myoclonic_epilepsy).[8] Two transcript variants encoding distinct isoforms have been identified for this gene.[7] In [melanocytic cells](/source/Melanocyte) ASAH1 gene expression may be regulated by [MITF](/source/Microphthalmia-associated_transcription_factor).[9]

## As a glioblastoma drug target

ASAH1 expression is upregulated following radiation, suggesting it plays a role in conferring radioresistance to [glioblastoma](/source/Glioblastoma) and in the development of recurrent glioblastoma.[10] Inhibiting the activity of ASAH1 with [carmofur](/source/Carmofur), a drug that has been approved for clinical treatment of [colorectal cancers](/source/Colorectal_cancer) in several countries, leads to substantial cell deaths and as a result has been proposed as a drug target in the treatment of glioblastoma.[11] It has also been suggested to be a novel drug target against pediatric brain tumors as well.[12]

## References

1. ^ [***a***](#cite_ref-refGRCh38Ensembl_1-0) [***b***](#cite_ref-refGRCh38Ensembl_1-1) [***c***](#cite_ref-refGRCh38Ensembl_1-2) [GRCh38: Ensembl release 89: ENSG00000104763](http://May2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000104763) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. ^ [***a***](#cite_ref-refGRCm38Ensembl_2-0) [***b***](#cite_ref-refGRCm38Ensembl_2-1) [***c***](#cite_ref-refGRCm38Ensembl_2-2) [GRCm38: Ensembl release 89: ENSMUSG00000031591](http://May2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000031591) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. **[^](#cite_ref-3)** ["Human PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=427). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-4)** ["Mouse PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=11886). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-pmid8955159_5-0)** Koch J, Gärtner S, Li CM, Quintern LE, Bernardo K, Levran O, Schnabel D, Desnick RJ, Schuchman EH, Sandhoff K (December 1996). ["Molecular cloning and characterization of a full-length complementary DNA encoding human acid ceramidase. Identification Of the first molecular lesion causing Farber disease"](https://doi.org/10.1074%2Fjbc.271.51.33110). *The Journal of Biological Chemistry*. **271** (51): 33110–5. [doi](/source/Doi_(identifier)):[10.1074/jbc.271.51.33110](https://doi.org/10.1074%2Fjbc.271.51.33110). [PMID](/source/PMID_(identifier)) [8955159](https://pubmed.ncbi.nlm.nih.gov/8955159).

1. **[^](#cite_ref-pmid10610716_6-0)** Li CM, Park JH, He X, Levy B, Chen F, Arai K, Adler DA, Disteche CM, Koch J, Sandhoff K, Schuchman EH (December 1999). "The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis, and expression". *Genomics*. **62** (2): 223–31. [doi](/source/Doi_(identifier)):[10.1006/geno.1999.5940](https://doi.org/10.1006%2Fgeno.1999.5940). [PMID](/source/PMID_(identifier)) [10610716](https://pubmed.ncbi.nlm.nih.gov/10610716).

1. ^ [***a***](#cite_ref-entrez_7-0) [***b***](#cite_ref-entrez_7-1) ["Entrez Gene: ASAH1 N-acylsphingosine amidohydrolase (acid ceramidase) 1"](https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=427).

1. **[^](#cite_ref-8)** Zhou J, Tawk M, Tiziano FD, Veillet J, Bayes M, Nolent F, Garcia V, Servidei S, Bertini E, Castro-Giner F, Renda Y, Carpentier S, Andrieu-Abadie N, Gut I, Levade T, Topaloglu H, Melki J (July 2012). ["Spinal muscular atrophy associated with progressive myoclonic epilepsy is caused by mutations in ASAH1"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397266). *American Journal of Human Genetics*. **91** (1): 5–14. [doi](/source/Doi_(identifier)):[10.1016/j.ajhg.2012.05.001](https://doi.org/10.1016%2Fj.ajhg.2012.05.001). [PMC](/source/PMC_(identifier)) [3397266](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397266). [PMID](/source/PMID_(identifier)) [22703880](https://pubmed.ncbi.nlm.nih.gov/22703880).

1. **[^](#cite_ref-pmid19067971_9-0)** Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (December 2008). ["Novel MITF targets identified using a two-step DNA microarray strategy"](https://doi.org/10.1111%2Fj.1755-148X.2008.00505.x). *Pigment Cell & Melanoma Research*. **21** (6): 665–76. [doi](/source/Doi_(identifier)):[10.1111/j.1755-148X.2008.00505.x](https://doi.org/10.1111%2Fj.1755-148X.2008.00505.x). [PMID](/source/PMID_(identifier)) [19067971](https://pubmed.ncbi.nlm.nih.gov/19067971). [S2CID](/source/S2CID_(identifier)) [24698373](https://api.semanticscholar.org/CorpusID:24698373).

1. **[^](#cite_ref-10)** Doan NB, Nguyen HS, Al-Gizawiy MM, Mueller WM, Sabbadini RA, Rand SD, Connelly JM, Chitambar CR, Schmainda KM, Mirza SP (October 2017). ["Acid ceramidase confers radioresistance to glioblastoma cells"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652937). *Oncology Reports*. **38** (4): 1932–40. [doi](/source/Doi_(identifier)):[10.3892/or.2017.5855](https://doi.org/10.3892%2For.2017.5855). [PMC](/source/PMC_(identifier)) [5652937](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652937). [PMID](/source/PMID_(identifier)) [28765947](https://pubmed.ncbi.nlm.nih.gov/28765947).

1. **[^](#cite_ref-11)** Doan NB, Alhajala H, Al-Gizawiy MM, Mueller WM, Rand SD, Connelly JM, Cochran EJ, Chitambar CR, Clark P, Kuo J, Schmainda KM, Mirza SP (December 2017). ["Acid ceramidase and its inhibitors: a de novo drug target and a new class of drugs for killing glioblastoma cancer stem cells with high efficiency"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762539). *Oncotarget*. **8** (68): 112662–74. [doi](/source/Doi_(identifier)):[10.18632/oncotarget.22637](https://doi.org/10.18632%2Foncotarget.22637). [PMC](/source/PMC_(identifier)) [5762539](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762539). [PMID](/source/PMID_(identifier)) [29348854](https://pubmed.ncbi.nlm.nih.gov/29348854).

1. **[^](#cite_ref-12)** Doan NB, Nguyen HS, Montoure A, Al-Gizawiy MM, Mueller WM, Kurpad S, Rand SD, Connelly JM, Chitambar CR, Schmainda KM, Mirza SP (April 2017). ["Acid ceramidase is a novel drug target for pediatric brain tumors"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421885). *Oncotarget*. **8** (15): 24753–61. [doi](/source/Doi_(identifier)):[10.18632/oncotarget.15800](https://doi.org/10.18632%2Foncotarget.15800). [PMC](/source/PMC_(identifier)) [5421885](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421885). [PMID](/source/PMID_(identifier)) [28445970](https://pubmed.ncbi.nlm.nih.gov/28445970).

## External links

- Human [*ASAH1*](https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&singleSearch=knownCanonical&position=ASAH1) genome location and [*ASAH1*](https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_type=knownGene&hgg_gene=ASAH1) gene details page in the [UCSC Genome Browser](/source/UCSC_Genome_Browser).

## Further reading

- Perry DK, Hannun YA (December 1998). "The role of ceramide in cell signaling". *Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids*. **1436** (1–2): 233–43. [doi](/source/Doi_(identifier)):[10.1016/S0005-2760(98)00145-3](https://doi.org/10.1016%2FS0005-2760%2898%2900145-3). [PMID](/source/PMID_(identifier)) [9838138](https://pubmed.ncbi.nlm.nih.gov/9838138).

- Bernardo K, Hurwitz R, Zenk T, Desnick RJ, Ferlinz K, Schuchman EH, Sandhoff K (May 1995). ["Purification, characterization, and biosynthesis of human acid ceramidase"](https://doi.org/10.1074%2Fjbc.270.19.11098). *The Journal of Biological Chemistry*. **270** (19): 11098–102. [doi](/source/Doi_(identifier)):[10.1074/jbc.270.19.11098](https://doi.org/10.1074%2Fjbc.270.19.11098). [PMID](/source/PMID_(identifier)) [7744740](https://pubmed.ncbi.nlm.nih.gov/7744740).

- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". *Gene*. **138** (1–2): 171–4. [doi](/source/Doi_(identifier)):[10.1016/0378-1119(94)90802-8](https://doi.org/10.1016%2F0378-1119%2894%2990802-8). [PMID](/source/PMID_(identifier)) [8125298](https://pubmed.ncbi.nlm.nih.gov/8125298).

- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". *Gene*. **200** (1–2): 149–56. [doi](/source/Doi_(identifier)):[10.1016/S0378-1119(97)00411-3](https://doi.org/10.1016%2FS0378-1119%2897%2900411-3). [PMID](/source/PMID_(identifier)) [9373149](https://pubmed.ncbi.nlm.nih.gov/9373149).

- Seelan RS, Qian C, Yokomizo A, Bostwick DG, Smith DI, Liu W (October 2000). "Human acid ceramidase is overexpressed but not mutated in prostate cancer". *Genes, Chromosomes & Cancer*. **29** (2): 137–46. [doi](/source/Doi_(identifier)):[10.1002/1098-2264(2000)9999:9999<::AID-GCC1018>3.0.CO;2-E](https://doi.org/10.1002%2F1098-2264%282000%299999%3A9999%3C%3A%3AAID-GCC1018%3E3.0.CO%3B2-E). [PMID](/source/PMID_(identifier)) [10959093](https://pubmed.ncbi.nlm.nih.gov/10959093). [S2CID](/source/S2CID_(identifier)) [21766341](https://api.semanticscholar.org/CorpusID:21766341).

- Strelow A, Bernardo K, Adam-Klages S, Linke T, Sandhoff K, Krönke M, Adam D (September 2000). ["Overexpression of acid ceramidase protects from tumor necrosis factor-induced cell death"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193270). *The Journal of Experimental Medicine*. **192** (5): 601–12. [doi](/source/Doi_(identifier)):[10.1084/jem.192.5.601](https://doi.org/10.1084%2Fjem.192.5.601). [PMC](/source/PMC_(identifier)) [2193270](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193270). [PMID](/source/PMID_(identifier)) [10974027](https://pubmed.ncbi.nlm.nih.gov/10974027).

- Bär J, Linke T, Ferlinz K, Neumann U, Schuchman EH, Sandhoff K (March 2001). ["Molecular analysis of acid ceramidase deficiency in patients with Farber disease"](https://doi.org/10.1002%2Fhumu.5). *Human Mutation*. **17** (3): 199–209. [doi](/source/Doi_(identifier)):[10.1002/humu.5](https://doi.org/10.1002%2Fhumu.5). [PMID](/source/PMID_(identifier)) [11241842](https://pubmed.ncbi.nlm.nih.gov/11241842). [S2CID](/source/S2CID_(identifier)) [39656479](https://api.semanticscholar.org/CorpusID:39656479).

- Ferlinz K, Kopal G, Bernardo K, Linke T, Bar J, Breiden B, Neumann U, Lang F, Schuchman EH, Sandhoff K (September 2001). ["Human acid ceramidase: processing, glycosylation, and lysosomal targeting"](https://doi.org/10.1074%2Fjbc.M103066200). *The Journal of Biological Chemistry*. **276** (38): 35352–60. [doi](/source/Doi_(identifier)):[10.1074/jbc.M103066200](https://doi.org/10.1074%2Fjbc.M103066200). [PMID](/source/PMID_(identifier)) [11451951](https://pubmed.ncbi.nlm.nih.gov/11451951).

- Muramatsu T, Sakai N, Yanagihara I, Yamada M, Nishigaki T, Kokubu C, Tsukamoto H, Ito M, Inui K (November 2002). ["Mutation analysis of the acid ceramidase gene in Japanese patients with Farber disease"](https://doi.org/10.1023%2FA%3A1022047408477). *Journal of Inherited Metabolic Disease*. **25** (7): 585–92. [doi](/source/Doi_(identifier)):[10.1023/A:1022047408477](https://doi.org/10.1023%2FA%3A1022047408477). [PMID](/source/PMID_(identifier)) [12638942](https://pubmed.ncbi.nlm.nih.gov/12638942). [S2CID](/source/S2CID_(identifier)) [26208268](https://api.semanticscholar.org/CorpusID:26208268).

- Zhang H, Li XJ, Martin DB, Aebersold R (June 2003). "Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry". *Nature Biotechnology*. **21** (6): 660–6. [doi](/source/Doi_(identifier)):[10.1038/nbt827](https://doi.org/10.1038%2Fnbt827). [PMID](/source/PMID_(identifier)) [12754519](https://pubmed.ncbi.nlm.nih.gov/12754519). [S2CID](/source/S2CID_(identifier)) [581283](https://api.semanticscholar.org/CorpusID:581283).

- Okino N, He X, Gatt S, Sandhoff K, Ito M, Schuchman EH (August 2003). ["The reverse activity of human acid ceramidase"](https://doi.org/10.1074%2Fjbc.M303310200). *The Journal of Biological Chemistry*. **278** (32): 29948–53. [doi](/source/Doi_(identifier)):[10.1074/jbc.M303310200](https://doi.org/10.1074%2Fjbc.M303310200). [PMID](/source/PMID_(identifier)) [12764132](https://pubmed.ncbi.nlm.nih.gov/12764132).

- He X, Okino N, Dhami R, Dagan A, Gatt S, Schulze H, Sandhoff K, Schuchman EH (August 2003). ["Purification and characterization of recombinant, human acid ceramidase. Catalytic reactions and interactions with acid sphingomyelinase"](https://doi.org/10.1074%2Fjbc.M301936200). *The Journal of Biological Chemistry*. **278** (35): 32978–86. [doi](/source/Doi_(identifier)):[10.1074/jbc.M301936200](https://doi.org/10.1074%2Fjbc.M301936200). [PMID](/source/PMID_(identifier)) [12815059](https://pubmed.ncbi.nlm.nih.gov/12815059).

- Hara S, Nakashima S, Kiyono T, Sawada M, Yoshimura S, Iwama T, Banno Y, Shinoda J, Sakai N (August 2004). ["p53-Independent ceramide formation in human glioma cells during gamma-radiation-induced apoptosis"](https://doi.org/10.1038%2Fsj.cdd.4401428). *Cell Death and Differentiation*. **11** (8): 853–61. [doi](/source/Doi_(identifier)):[10.1038/sj.cdd.4401428](https://doi.org/10.1038%2Fsj.cdd.4401428). [PMID](/source/PMID_(identifier)) [15088070](https://pubmed.ncbi.nlm.nih.gov/15088070).

- Lewandrowski U, Moebius J, Walter U, Sickmann A (February 2006). ["Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach"](https://doi.org/10.1074%2Fmcp.M500324-MCP200). *Molecular & Cellular Proteomics*. **5** (2): 226–33. [doi](/source/Doi_(identifier)):[10.1074/mcp.M500324-MCP200](https://doi.org/10.1074%2Fmcp.M500324-MCP200). [PMID](/source/PMID_(identifier)) [16263699](https://pubmed.ncbi.nlm.nih.gov/16263699).

v t e Metabolism, lipid metabolism, glycolipid enzymes Sphingolipid To glycosphingolipid Glycosyltransferase Sulfotransferase To ceramide From ganglioside β-Galactosidase Hexosaminidase A Neuraminidase Glucocerebrosidase From globoside Hexosaminidase B α-Galactosidase β-Galactosidase Glucocerebrosidase From sphingomyelin Sphingomyelin phosphodiesterase Sphingomyelin phosphodiesterase 1 From sulfatide Arylsulfatase A Galactosylceramidase To sphingosine Ceramidase ACER1 ACER2 ACER3 ASAH1 ASAH2 ASAH2B ASAH2C Other Sphingosine kinase NCL Palmitoyl protein thioesterase Tripeptidyl peptidase I CLN3 CLN5 CLN6 CLN8 Ceramide synthesis Serine C-palmitoyltransferase (SPTLC1) Ceramide glucosyltransferase (UGCG)

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