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    SACS sacsin molecular chaperone [ Homo sapiens (human) ]

    Gene ID: 26278, updated on 10-Dec-2024

    Summary

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    Official Symbol
    SACSprovided by HGNC
    Official Full Name
    sacsin molecular chaperoneprovided by HGNC
    Primary source
    HGNC:HGNC:10519
    See related
    Ensembl:ENSG00000151835 MIM:604490; AllianceGenome:HGNC:10519
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    SPAX6; ARSACS; DNAJC29; PPP1R138
    Summary
    This gene encodes the sacsin protein, which includes a UbL domain at the N-terminus, a DnaJ domain, and a HEPN domain at the C-terminus. The gene is highly expressed in the central nervous system, also found in skin, skeletal muscles and at low levels in the pancreas. This gene includes a very large exon spanning more than 12.8 kb. 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. The authors of a publication on the effects of siRNA-mediated sacsin knockdown concluded that sacsin protects against mutant ataxin-1 and suggest that "the large multi-domain sacsin protein is able to recruit Hsp70 chaperone action and has the potential to regulate the effects of other ataxia proteins" (Parfitt et al., PubMed: 19208651). A pseudogene associated with this gene is located on chromosome 11. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2013]
    Expression
    Ubiquitous expression in brain (RPKM 7.1), appendix (RPKM 2.8) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See SACS in Genome Data Viewer
    Location:
    13q12.12
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (23328830..23433702, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (22535642..22640549, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (23902969..24007841, complement)

    Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene sarcoglycan gamma Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7449 Neighboring gene SDA1 domain containing 1 pseudogene 4 Neighboring gene uncharacterized LOC107984585 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7450 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7451 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5171 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5172 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7452 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7453 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7454 Neighboring gene ribosomal protein lateral stalk subunit P1 pseudogene 13 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr13:24007093-24007660 Neighboring gene SACS antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:24014794-24015294 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:24015295-24015795 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr13:24022765-24023604 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7455 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_32713 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5173 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7456 Neighboring gene long intergenic non-protein coding RNA 327 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:24066632-24067132 Neighboring gene uncharacterized LOC124903135 Neighboring gene NANOG hESC enhancer GRCh37_chr13:24081975-24082502 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr13:24100455-24101050

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Cerebellar cognitive affective syndrome and autosomal recessive spastic ataxia of charlevoix-saguenay: a report of two male sibs. Verhoeven WM, et al. Psychopathology, 2012. PMID 22441213
    2. Mutations in SACS cause atypical and late-onset forms of ARSACS. Baets J, et al. Neurology, 2010 Sep 28. PMID 20876471
    3. Characteristic MRI and funduscopic findings help diagnose ARSACS outside Quebec. Gerwig M, et al. Neurology, 2010 Dec 7. PMID 21135390
    4. Myelinated retinal fibers in autosomal recessive spastic ataxia of Charlevoix-Saguenay. Vingolo EM, et al. Eur J Neurol, 2011 Sep. PMID 21410841
    5. Computational analysis of a novel SACS gene mutation with BioExtract server. Bouhlal Y, et al. J Mol Neurosci, 2011 May. PMID 21416271

    See all (121) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The J Domain of Sacsin Disrupts Intermediate Filament Assembly.
      Title: The J Domain of Sacsin Disrupts Intermediate Filament Assembly.
    2. The ARSACS disease protein sacsin controls lysosomal positioning and reformation by regulating microtubule dynamics.
      Title: The ARSACS disease protein sacsin controls lysosomal positioning and reformation by regulating microtubule dynamics.
    3. Autosomal recessive spastic ataxia of Charlevoix-Saguenay caused by novel mutations in SACS gene: A report of two Chinese families.
      Title: Autosomal recessive spastic ataxia of Charlevoix-Saguenay caused by novel mutations in SACS gene: A report of two Chinese families.
    4. Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth.
      Title: Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth.
    5. A novel SACS p.Pro4154GlnfsTer20 mutation in a family with autosomal recessive spastic ataxia of Charlevoix-Saguenay.
      Title: A novel SACS p.Pro4154GlnfsTer20 mutation in a family with autosomal recessive spastic ataxia of Charlevoix-Saguenay.
    6. A novel homozygous SACS mutation identified by whole exome sequencing-genotype phenotype correlations of all published cases.
      Title: A novel homozygous SACS mutation identified by whole exome sequencing-genotype phenotype correlations of all published cases.
    7. Loss of SACSIN expression is associated with autosomal recessive spastic ataxia of the Charlevoix-Saguenay.
      Title: Sacsin, mutated in the ataxia ARSACS, regulates intermediate filament assembly and dynamics.
    8. novel pathogenic mutation of the SACS gene was discovered
      Title: [Analysis of SACS mutation in a family affected with autosomal recessive spastic ataxia of Charlevoix-Saguenay].
    9. The c.5236dupA (p.T1746fs) and c.13085T to G (p.I4362R) mutations of the SACS gene probably underlie spastic ataxia of Charlevoix-Saguenay
      Title: [Identification of compound heterozygous mutations of SACS gene in two patients from a pedigree with spastic ataxia of Charlevoix-Saguenay].
    10. Novel homozygous variants in ATCAY, MCOLN1, and SACS in a complex movement disorder in five consanguineous Pakistani families.
      Title: Novel homozygous variants in ATCAY, MCOLN1, and SACS in complex neurological disorders.
    Submit: New GeneRIF Correction See all GeneRIFs (51)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Charlevoix-Saguenay spastic ataxia
    MedGen: C1849140 OMIM: 270550 GeneReviews: Hereditary Ataxia Overview, ARSACS
    		Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide association study identifies protein quantitative trait loci (pQTLs).
    EBI GWAS Catalog
    Gene-Smoking Interactions Identify Several Novel Blood Pressure Loci in the Framingham Heart Study.
    EBI GWAS Catalog
    Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India.
    EBI GWAS Catalog
    Novel associations for hypothyroidism include known autoimmune risk loci.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • DKFZp686B15167

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables Hsp70 protein binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables Hsp70 protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables low-density lipoprotein particle receptor binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables proteasome binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein-folding chaperone binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in negative regulation of inclusion body assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein folding NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in axon TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in cell body fiber TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in dendrite TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    sacsin
    Names
    dnaJ homolog subfamily C member 29
    protein phosphatase 1, regulatory subunit 138
    spastic ataxia of Charlevoix-Saguenay (sacsin)

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_012342.1 RefSeqGene

      Range
      5001..109873
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001278055.2 → NP_001264984.1  sacsin isoform 2

      See identical proteins and their annotated locations for NP_001264984.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in its 5' UTR, lacks a segment of the 5' coding region and initiates translation at an in-frame downstream start codon, compared to variant 1. It encodes isoform 2 which is shorter than isoform 1 at the N-terminus.
      Source sequence(s)
      AK125458, AL157766, DB309987
      Conserved Domains (2) summary
      smart00748
      Location:4304 → 4420
      HEPN; Higher Eukarytoes and Prokaryotes Nucleotide-binding domain
      cl02542
      Location:4175 → 4213
      DnaJ; DnaJ domain or J-domain. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, ...

    2. NM_014363.6 → NP_055178.3  sacsin isoform 1

      See identical proteins and their annotated locations for NP_055178.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AK125458, AL157766, AW295072, AW296712, DB213398, DB309987
      Consensus CDS
      CCDS9300.2
      UniProtKB/Swiss-Prot
      O94835, Q5T9J5, Q5T9J7, Q5T9J8, Q68DF5, Q6MZR4, Q8NBF9, Q9NZJ4
      Related
      ENSP00000371729.3, ENST00000382292.9
      Conserved Domains (3) summary
      cd01769
      Location:19 → 60
      UBL; Ubiquitin-like domain of UBL
      smart00748
      Location:4451 → 4567
      HEPN; Higher Eukarytoes and Prokaryotes Nucleotide-binding domain
      cl02542
      Location:4322 → 4360
      DnaJ; DnaJ domain or J-domain. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, ...

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

      Range
      23328830..23433702 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047430261.1 → XP_047286217.1  sacsin isoform X10

    2. XM_047430257.1 → XP_047286213.1  sacsin isoform X7

    3. XM_005266338.3 → XP_005266395.1  sacsin isoform X2

      UniProtKB/TrEMBL
      A0A804HIQ1
      Related
      ENSP00000507173.1, ENST00000682944.1
      Conserved Domains (3) summary
      cd01769
      Location:19 → 60
      UBL; Ubiquitin-like domain of UBL
      smart00748
      Location:4460 → 4576
      HEPN; Higher Eukarytoes and Prokaryotes Nucleotide-binding domain
      cl28246
      Location:4318 → 4379
      DnaJ; DnaJ-class molecular chaperone with C-terminal Zn finger domain [Posttranslational modification, protein turnover, chaperones]

    4. XM_047430262.1 → XP_047286218.1  sacsin isoform X10

    5. XM_047430258.1 → XP_047286214.1  sacsin isoform X7

    6. XM_047430256.1 → XP_047286212.1  sacsin isoform X5

      UniProtKB/Swiss-Prot
      O94835, Q5T9J5, Q5T9J7, Q5T9J8, Q68DF5, Q6MZR4, Q8NBF9, Q9NZJ4

    7. XM_024449337.2 → XP_024305105.1  sacsin isoform X2

      UniProtKB/TrEMBL
      A0A804HIQ1
      Conserved Domains (3) summary
      cd01769
      Location:19 → 60
      UBL; Ubiquitin-like domain of UBL
      smart00748
      Location:4460 → 4576
      HEPN; Higher Eukarytoes and Prokaryotes Nucleotide-binding domain
      cl28246
      Location:4318 → 4379
      DnaJ; DnaJ-class molecular chaperone with C-terminal Zn finger domain [Posttranslational modification, protein turnover, chaperones]

    8. XM_047430259.1 → XP_047286215.1  sacsin isoform X8

    9. XM_047430255.1 → XP_047286211.1  sacsin isoform X3

    10. XM_047430254.1 → XP_047286210.1  sacsin isoform X1

    11. XM_047430263.1 → XP_047286219.1  sacsin isoform X11

    12. XM_047430260.1 → XP_047286216.1  sacsin isoform X9

    13. XM_017020539.2 → XP_016876028.1  sacsin isoform X6

    14. XM_011535039.3 → XP_011533341.1  sacsin isoform X4

      Conserved Domains (3) summary
      cd01769
      Location:16 → 57
      UBL; Ubiquitin-like domain of UBL
      smart00748
      Location:4457 → 4573
      HEPN; Higher Eukarytoes and Prokaryotes Nucleotide-binding domain
      cl02542
      Location:4328 → 4366
      DnaJ; DnaJ domain or J-domain. DnaJ/Hsp40 (heat shock protein 40) proteins are highly conserved and play crucial roles in protein translation, folding, unfolding, translocation, and degradation. They act primarily by stimulating the ATPase activity of Hsp70s, ...

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060937.1 Alternate T2T-CHM13v2.0

      Range
      22535642..22640549 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054374430.1 → XP_054230405.1  sacsin isoform X5

      UniProtKB/Swiss-Prot
      O94835, Q5T9J5, Q5T9J7, Q5T9J8, Q68DF5, Q6MZR4, Q8NBF9, Q9NZJ4

    2. XM_054374437.1 → XP_054230412.1  sacsin isoform X10

    3. XM_054374433.1 → XP_054230408.1  sacsin isoform X7

    4. XM_054374427.1 → XP_054230402.1  sacsin isoform X2

      UniProtKB/TrEMBL
      A0A804HIQ1

    5. XM_054374436.1 → XP_054230411.1  sacsin isoform X10

    6. XM_054374432.1 → XP_054230407.1  sacsin isoform X7

    7. XM_054374426.1 → XP_054230401.1  sacsin isoform X2

      UniProtKB/TrEMBL
      A0A804HIQ1

    8. XM_054374431.1 → XP_054230406.1  sacsin isoform X6

    9. XM_054374429.1 → XP_054230404.1  sacsin isoform X4

    10. XM_054374428.1 → XP_054230403.1  sacsin isoform X3

    11. XM_054374438.1 → XP_054230413.1  sacsin isoform X11

    12. XM_054374435.1 → XP_054230410.1  sacsin isoform X9

    13. XM_054374425.1 → XP_054230400.1  sacsin isoform X1

    14. XM_054374434.1 → XP_054230409.1  sacsin isoform X8

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_152752.1: Suppressed sequence

      Description
      NM_152752.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NZJ4.2 GenPept UniProtKB/Swiss-Prot:Q9NZJ4

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