Sphingomyelin phosphodiesterase 1 explained

Sphingomyelin phosphodiesterase 1 (SMPD1), also known as acid sphingomyelinase (ASM), is an enzyme that in humans is encoded by the SMPD1 gene.

Sphingomyelin phosphodiesterase 1 belongs to the sphingomyelin phosphodiesterase family.^[1]

Clinical significance

Defects in the SMPD1 gene cause Niemann–Pick disease, SMPD1-associated.^[1]

A mutation from leucine to proline at amino acid residue 302 encoded by the SMPD1 gene was identified by Gan-Or et al. (2013) as a risk factor for Parkinson disease.^[2]

Further reading

• Stoffel W . Functional analysis of acid and neutral sphingomyelinases in vitro and in vivo . Chemistry and Physics of Lipids . 102 . 1–2 . 107–21 . November 1999 . 11001565 . 10.1016/S0009-3084(99)00079-1 .
• Newrzella D, Stoffel W . Molecular cloning of the acid sphingomyelinase of the mouse and the organization and complete nucleotide sequence of the gene . Biological Chemistry Hoppe-Seyler . 373 . 12 . 1233–8 . December 1992 . 1292508 . 10.1515/bchm3.1992.373.2.1233 .
• Takahashi T, Desnick RJ, Takada G, Schuchman EH . Identification of a missense mutation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease . Human Mutation . 1 . 1 . 70–1 . 1993 . 1301192 . 10.1002/humu.1380010111 . 31754300 .
• Levran O, Desnick RJ, Schuchman EH . Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients . Blood . 80 . 8 . 2081–7 . October 1992 . 1391960 . 10.1182/blood.V80.8.2081.2081. free .
• Takahashi T, Suchi M, Desnick RJ, Takada G, Schuchman EH . Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms . The Journal of Biological Chemistry . 267 . 18 . 12552–8 . June 1992 . 10.1016/S0021-9258(18)42312-5 . 1618760 . free .
• Schuchman EH, Levran O, Suchi M, Desnick RJ . An MspI polymorphism in the human acid sphingomyelinase gene (SMPD1) . Nucleic Acids Research . 19 . 11 . 3160 . June 1991 . 1711683 . 328296 . 10.1093/nar/19.11.3160 .
• Ferlinz K, Hurwitz R, Sandhoff K . Molecular basis of acid sphingomyelinase deficiency in a patient with Niemann-Pick disease type A . Biochemical and Biophysical Research Communications . 179 . 3 . 1187–91 . September 1991 . 1718266 . 10.1016/0006-291X(91)91697-B .
• Schuchman EH, Levran O, Pereira LV, Desnick RJ . Structural organization and complete nucleotide sequence of the gene encoding human acid sphingomyelinase (SMPD1) . Genomics . 12 . 2 . 197–205 . February 1992 . 1740330 . 10.1016/0888-7543(92)90366-Z .
• Schuchman EH, Suchi M, Takahashi T, Sandhoff K, Desnick RJ . Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs . The Journal of Biological Chemistry . 266 . 13 . 8531–9 . May 1991 . 10.1016/S0021-9258(18)93007-3 . 1840600 . free .
• Levran O, Desnick RJ, Schuchman EH . Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients . The Journal of Clinical Investigation . 88 . 3 . 806–10 . September 1991 . 1885770 . 295465 . 10.1172/JCI115380 .
• da Veiga Pereira L, Desnick RJ, Adler DA, Disteche CM, Schuchman EH . Regional assignment of the human acid sphingomyelinase gene (SMPD1) by PCR analysis of somatic cell hybrids and in situ hybridization to 11p15.1----p15.4 . Genomics . 9 . 2 . 229–34 . February 1991 . 2004772 . 10.1016/0888-7543(91)90246-B .
• Levran O, Desnick RJ, Schuchman EH . Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients . Proceedings of the National Academy of Sciences of the United States of America . 88 . 9 . 3748–52 . May 1991 . 2023926 . 51530 . 10.1073/pnas.88.9.3748 . 1991PNAS...88.3748L . free .
• Quintern LE, Schuchman EH, Levran O, Suchi M, Ferlinz K, Reinke H, Sandhoff K, Desnick RJ . Isolation of cDNA clones encoding human acid sphingomyelinase: occurrence of alternatively processed transcripts . The EMBO Journal . 8 . 9 . 2469–73 . September 1989 . 2555181 . 401234 . 10.1002/j.1460-2075.1989.tb08382.x.
• Horinouchi K, Erlich S, Perl DP, Ferlinz K, Bisgaier CL, Sandhoff K, Desnick RJ, Stewart CL, Schuchman EH . Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease . Nature Genetics . 10 . 3 . 288–93 . July 1995 . 7670466 . 10.1038/ng0795-288 . 37065681 .
• Sperl W, Bart G, Vanier MT, Christomanou H, Baldissera I, Steichen-Gersdorf E, Paschke E . A family with visceral course of Niemann-Pick disease, macular halo syndrome and low sphingomyelin degradation rate . Journal of Inherited Metabolic Disease . 17 . 1 . 93–103 . 1994 . 8051942 . 10.1007/BF00735404 . 12743175 .
• Ida H, Rennert OM, Eto Y, Chan WY . Cloning of a human acid sphingomyelinase cDNA with a new mutation that renders the enzyme inactive . Journal of Biochemistry . 114 . 1 . 15–20 . July 1993 . 8407868 . 10.1093/oxfordjournals.jbchem.a124131.
• Ida H, Rennert OM, Maekawa K, Eto Y . Identification of three novel mutations in the acid sphinogomyelinase gene of Japanese patients with Niemann-Pick disease type A and B . Human Mutation . 7 . 1 . 65–7 . 1996 . 8664904 . 10.1002/(SICI)1098-1004(1996)7:1<65::AID-HUMU10>3.0.CO;2-Q . 6033746 . free .
• Schuchman EH . Two new mutations in the acid sphingomyelinase gene causing type a Niemann-pick disease: N389T and R441X . Human Mutation . 6 . 4 . 352–4 . 1996 . 8680412 . 10.1002/humu.1380060412 . 44787586 . free .
• Takahashi T, Suchi M, Sato W, Ten SB, Sakuragawa N, Desnick RJ, Schuchman EH, Takada G . Identification and expression of a missense mutation (Y446C) in the acid sphingomyelinase gene from a Japanese patient with type A Niemann-Pick disease . The Tohoku Journal of Experimental Medicine . 177 . 2 . 117–23 . October 1995 . 8693491 . 10.1620/tjem.177.117 . free .
• Ferlinz K, Hurwitz R, Moczall H, Lansmann S, Schuchman EH, Sandhoff K . Functional characterization of the N-glycosylation sites of human acid sphingomyelinase by site-directed mutagenesis . European Journal of Biochemistry . 243 . 1–2 . 511–7 . January 1997 . 9030779 . 10.1111/j.1432-1033.1997.511_1a.x . free .

External links

• GeneReviews/NCBI/NIH/UW entry on Acid Sphingomyelinase Deficiency Includes: Niemann-Pick Disease Type A, Niemann-Pick Disease Type B
• OMIM entries on Acid Sphingomyelinase Deficiency

Notes and References

1. Web site: Entrez Gene: SMPD1 sphingomyelin phosphodiesterase 1, acid lysosomal (acid sphingomyelinase).
2. Gan-Or Z, Ozelius LJ, Bar-Shira A, Saunders-Pullman R, Mirelman A, Kornreich R, Gana-Weisz M, Raymond D, Rozenkrantz L, Deik A, Gurevich T, Gross SJ, Schreiber-Agus N, Giladi N, Bressman SB, Orr-Urtreger A . The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease . Neurology . 80 . 17 . 1606–10 . April 2013 . 23535491 . 3662322 . 10.1212/WNL.0b013e31828f180e .