GeneBe

SACS

sacsin molecular chaperone, the group of Protein phosphatase 1 regulatory subunits|DNAJ (HSP40) heat shock proteins

Basic information

Region (hg38): 13:23288689-23433763

Links

ENSG00000151835 ∙ NCBI:26278 ∙ OMIM:604490 ∙ HGNC:10519 ∙ Uniprot:Q9NZJ4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • Charlevoix-Saguenay spastic ataxia (Definitive), mode of inheritance: AR
  • Charlevoix-Saguenay spastic ataxia (Strong), mode of inheritance: AR
  • Charlevoix-Saguenay spastic ataxia (Definitive), mode of inheritance: AR
  • Charlevoix-Saguenay spastic ataxia (Supportive), mode of inheritance: AR
  • Charlevoix-Saguenay spastic ataxia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Spastic ataxia, Charlevoix-Saguenay typeARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingMusculoskeletal; Neurologic; Ophthalmologic10655055; 12873855; 14718706; 14718708; 15985586; 18398442; 20876471; 21745802; 21993619; 22209141; 22892508; 27133561

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SACS gene.

  • Spastic_paraplegia (3317 variants)
  • Charlevoix-Saguenay_spastic_ataxia (1609 variants)
  • not_provided (674 variants)
  • Inborn_genetic_diseases (437 variants)
  • not_specified (184 variants)
  • Hereditary_spastic_paraplegia (144 variants)
  • SACS-related_disorder (76 variants)
  • See_cases (5 variants)
  • Intellectual_disability (4 variants)
  • Autosomal_recessive_spastic_ataxia (4 variants)
  • Hereditary_ataxia (3 variants)
  • Abnormal_central_motor_function (3 variants)
  • Spastic_ataxia (3 variants)
  • Abnormal_brain_morphology (2 variants)
  • Charcot-Marie-Tooth_disease (2 variants)
  • Charcot-Marie-Tooth_disease_X-linked_dominant_1 (1 variants)
  • Ataxia,_spastic,_childhood-onset,_autosomal_recessive,_with_optic_atrophy_and_intellectual_disability (1 variants)
  • Myoepithelial_tumor (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SACS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000014363.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
57
clinvar
1698
clinvar
25
clinvar
 1781
missense
15
clinvar
64
clinvar
928
clinvar
777
clinvar
55
clinvar
 1839
nonsense
112
clinvar
162
clinvar
4
clinvar
 278
start loss
2
 2
frameshift
211
clinvar
372
clinvar
9
clinvar
 592
splice donor/acceptor (+/-2bp)
15
clinvar
1
clinvar
 16
Total 338 616 999 2475 80

Highest pathogenic variant AF is 0.000109135646

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SACSprotein_codingprotein_codingENST00000382298 9104877
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
1.09e-231.0012550202461257480.000979
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.93821322.26e+30.9440.00011530262
Missense in Polyphen11021321.10.8341317801
Synonymous-1.488928381.060.00004388723
Loss of Function6.42661510.4370.000008622132

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001920.00192
Ashkenazi Jewish0.0007130.000695
East Asian0.001030.00103
Finnish0.0003710.000370
European (Non-Finnish)0.001190.00119
Middle Eastern0.001030.00103
South Asian0.0008910.000882
Other0.0005020.000489

dbNSFP

Source: dbNSFP

Function
FUNCTION: Co-chaperone which acts as a regulator of the Hsp70 chaperone machinery and may be involved in the processing of other ataxia-linked proteins. {ECO:0000269|PubMed:19208651}.;
Disease
DISEASE: Spastic ataxia Charlevoix-Saguenay type (SACS) [MIM:270550]: A neurodegenerative disease characterized by early- onset cerebellar ataxia, spasticity, retinal hypermyelination, pyramidal signs, and both axonal and demyelinating neuropathy with loss of sensory nerve conduction and reduced motor conduction velocities. Other features include dysarthria, distal muscle wasting, nystagmus, defect in conjugate pursuit ocular movements, retinal striation (from prominent retinal nerves) obscuring the retinal blood vessels in places, and the frequent presence of mitral valve prolapse. {ECO:0000269|PubMed:10655055, ECO:0000269|PubMed:12873855, ECO:0000269|PubMed:14718708, ECO:0000269|PubMed:15156359, ECO:0000269|PubMed:15985586, ECO:0000269|PubMed:16007637, ECO:0000269|PubMed:17290461, ECO:0000269|PubMed:17716690, ECO:0000269|PubMed:18398442, ECO:0000269|PubMed:18465152, ECO:0000269|PubMed:18484239, ECO:0000269|PubMed:19529988, ECO:0000269|PubMed:20876471, ECO:0000269|PubMed:27133561}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.309

Intolerance Scores

loftool
0.0165
rvis_EVS
-1.83
rvis_percentile_EVS
2.1

Haploinsufficiency Scores

pHI
0.665
hipred
N
hipred_score
0.427
ghis
0.529

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
gene_indispensability_pred
N
gene_indispensability_score
0.192

Gene Damage Prediction

AllRecessiveDominant
MendelianHighMediumHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Sacs
Phenotype
cellular phenotype; muscle phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Gene ontology

Biological process
protein folding;negative regulation of inclusion body assembly
Cellular component
nucleus;cytoplasm;mitochondrion;axon;dendrite;cell body fiber
Molecular function
Hsp70 protein binding;chaperone binding;proteasome binding