Sacsin

SACS
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1IUR, 3O10
Identifiers
Aliases	SACS, ARDNAJC29, PPP1R138, SPAX6, sacsin molecular chaperone
External IDs	OMIM: 604490; MGI: 1354724; HomoloGene: 8653; GeneCards: SACS; OMA:SACS - orthologs
Gene location (Human) Chr. Chromosome 13 (human) Band 13q12.12 Start 23,288,689 bp End 23,433,763 bp
Gene location (Mouse) Chr. Chromosome 14 (mouse) Band 14 D1|14 32.13 cM Start 61,375,906 bp End 61,478,144 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Brodmann area 23 middle frontal gyrus frontal pole Brodmann area 10 thoracic diaphragm Skeletal muscle tissue of rectus abdominis lateral nuclear group of thalamus middle temporal gyrus biceps brachii Skeletal muscle tissue of biceps brachii Top expressed in pontine nuclei deep cerebellar nuclei medial geniculate nucleus medial dorsal nucleus medial vestibular nucleus lateral geniculate nucleus inferior colliculi dorsal striatum substantia nigra primary motor cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function Hsp70 protein binding proteasome binding chaperone binding Cellular component cytoplasm axon dendrite mitochondrion nucleus cell body fiber Biological process protein folding negative regulation of inclusion body assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 26278 50720 Ensembl ENSG00000151835 ENSMUSG00000048279 UniProt Q9NZJ4 Q9JLC8 RefSeq (mRNA) NM_001278055 NM_014363 NM_152752 NM_015788 NM_172809 RefSeq (protein) NP_001264984 NP_055178 NP_766397 NP_056603 Location (UCSC) Chr 13: 23.29 – 23.43 Mb Chr 14: 61.38 – 61.48 Mb PubMed search
Wikidata
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Sacsin also known as DnaJ homolog subfamily C member 29 (DNAJC29) is a protein that in humans is encoded by the SACS gene. Sacsin is a Hsp70 co-chaperone.

Function

This gene consists of nine exons including a gigantic exon spanning more than 12.8k bp. It encodes the sacsin protein, which includes a UBQ region at the N-terminus, a HEPN domain at the C-terminus and a DnaJ region upstream of the HEPN domain. This modular protein is essential for normal mitochondrial network organization. The gene is highly expressed in the central nervous system, also found in skin, skeletal muscles and at low levels in the pancreas. Mutations in this gene result in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), a neurodegenerative disorder characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy.

Clinical significance

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a very rare neurodegenerative genetic disorder that results from mutations in the gene that produces Sacsin. Afflicted persons suffer from loss of balance, loss of muscle control and spasticity.

Further reading

• Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (October 1998). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 5 (5): 277–86. doi:10.1093/dnares/5.5.277. PMID 9872452.
• Engert JC, Bérubé P, Mercier J, Doré C, Lepage P, Ge B, Bouchard JP, Mathieu J, Melançon SB, Schalling M, Lander ES, Morgan K, Hudson TJ, Richter A (February 2000). "ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF". Nature Genetics. 24 (2): 120–5. doi:10.1038/72769. PMID 10655055. S2CID 19667726.
• Mercier J, Prévost C, Engert JC, Bouchard JP, Mathieu J, Richter A (2001). "Rapid detection of the sacsin mutations causing autosomal recessive spastic ataxia of Charlevoix-Saguenay". Genetic Testing. 5 (3): 255–9. doi:10.1089/10906570152742326. PMID 11788093.
• Criscuolo C, Banfi S, Orio M, Gasparini P, Monticelli A, Scarano V, Santorelli FM, Perretti A, Santoro L, De Michele G, Filla A (January 2004). "A novel mutation in SACS gene in a family from southern Italy". Neurology. 62 (1): 100–2. doi:10.1212/wnl.62.1.100. PMID 14718706. S2CID 42697050.
• Grieco GS, Malandrini A, Comanducci G, Leuzzi V, Valoppi M, Tessa A, Palmeri S, Benedetti L, Pierallini A, Gambelli S, Federico A, Pierelli F, Bertini E, Casali C, Santorelli FM (January 2004). "Novel SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay type". Neurology. 62 (1): 103–6. doi:10.1212/01.wnl.0000104491.66816.77. PMID 14718707. S2CID 8767156.
• Ogawa T, Takiyama Y, Sakoe K, Mori K, Namekawa M, Shimazaki H, Nakano I, Nishizawa M (January 2004). "Identification of a SACS gene missense mutation in ARSACS". Neurology. 62 (1): 107–9. doi:10.1212/01.wnl.0000099371.14478.73. PMID 14718708. S2CID 46133910.
• Richter AM, Ozgul RK, Poisson VC, Topaloglu H (September 2004). "Private SACS mutations in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) families from Turkey". Neurogenetics. 5 (3): 165–70. doi:10.1007/s10048-004-0179-y. PMID 15156359. S2CID 13187102.
• Shimazaki H, Takiyama Y, Sakoe K, Ando Y, Nakano I (June 2005). "A phenotype without spasticity in sacsin-related ataxia". Neurology. 64 (12): 2129–31. doi:10.1212/01.WNL.0000166031.91514.B3. PMID 15985586. S2CID 22975541.
• Yamamoto Y, Hiraoka K, Araki M, Nagano S, Shimazaki H, Takiyama Y, Sakoda S (December 2005). "Novel compound heterozygous mutations in sacsin-related ataxia". Journal of the Neurological Sciences. 239 (1): 101–4. doi:10.1016/j.jns.2005.08.005. PMID 16198375. S2CID 22286305.
• Ouyang Y, Takiyama Y, Sakoe K, Shimazaki H, Ogawa T, Nagano S, Yamamoto Y, Nakano I (April 2006). "Sacsin-related ataxia (ARSACS): expanding the genotype upstream from the gigantic exon". Neurology. 66 (7): 1103–4. doi:10.1212/01.wnl.0000204300.94261.ea. PMID 16606928. S2CID 19513985.
• Takado Y, Hara K, Shimohata T, Tokiguchi S, Onodera O, Nishizawa M (April 2007). "New mutation in the non-gigantic exon of SACS in Japanese siblings". Movement Disorders. 22 (5): 748–9. doi:10.1002/mds.21365. PMID 17290461. S2CID 23132322.

External links

• GeneReviews/NCBI/NIH/UW entry on ARSACS - Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay
• OMIM entries on ARSACS - Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay

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