Aliases: ARSACS, DNAJC29, PPP1R138, SPAX6
Chromosome No: 13
Chromosome Band: 13q12.12
Genetic Category: Rare single gene variant
ASD Reports: 7
Recent Reports: 0
Annotated variants: 10
Associated CNVs: 9
Evidence score: 3
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Relevance to Autism
TADA-de novo analysis of published de novo variants in nuclear-encoded mitochondrial-related genes (NEMGs) observed in 31,058 probands with undiagnosed developmental disorder (UDD), 10,318 ASD probands, and 4,262 controls in Luo et al., 2023 identified SACS as an ASD candidate gene with a false discovery rate less than 0.01 (FDR < 0.01); among the published ASD-associated variants in this gene that were used in the TADA analysis were a de novo loss-of-function variant and four de novo damaging missense variants (Yuen et al., 2017; Takata et al., 2018; Feliciano et al., 2019; Satterstrom et al., 2020). Additional de novo coding variants in SACS have been identified in ASD probands (Iossifov et al., 2014; Zhou et al., 2022).
Molecular Function
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.
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