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SACS sacsin molecular chaperone [ Homo sapiens (human) ]

Gene ID: 26278, updated on 7-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (23328830..23433702, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (22535642..22640549, complement)
105.20220307 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. The J Domain of Sacsin Disrupts Intermediate Filament Assembly. Dabbaghizadeh A, et al. Int J Mol Sci, 2022 Dec 12. PMID 36555380, Free PMC Article
  2. The ARSACS disease protein sacsin controls lysosomal positioning and reformation by regulating microtubule dynamics. Francis V, et al. J Biol Chem, 2022 Sep. PMID 35933016, Free PMC Article
  3. Autosomal recessive spastic ataxia of Charlevoix-Saguenay caused by novel mutations in SACS gene: A report of two Chinese families. Wang Z, et al. Neurosci Lett, 2021 May 1. PMID 33746006
  4. A novel SACS p.Pro4154GlnfsTer20 mutation in a family with autosomal recessive spastic ataxia of Charlevoix-Saguenay. Samanci B, et al. Neurol Sci, 2021 Jul. PMID 33559790
  5. A novel homozygous SACS mutation identified by whole exome sequencing-genotype phenotype correlations of all published cases. Xiromerisiou G, et al. J Mol Neurosci, 2020 Jan. PMID 31701440

See all (112) 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
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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)

Genotypes

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 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_2023_10

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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