|Institutional Source||Beutler Lab|
|Stock #||F6893 (G3) of strain busy|
|Chromosomal Location||61138457-61240695 bp(+) (GRCm38)|
|Type of Mutation||missense|
|DNA Base Change (assembly)||T to C at 61212976 bp|
|Amino Acid Change||Methionine to Threonine at position 4157 (M4157T)|
|Ref Sequence||ENSEMBL: ENSMUSP00000113377 (fasta)|
|Gene Model||predicted gene model for transcript(s): [ENSMUST00000119943]|
|Predicted Effect||probably benign
AA Change: M4157T
PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
AA Change: M4157T
|Meta Mutation Damage Score||0.102|
|Coding Region Coverage||
|Validation Efficiency||88% (165/188)|
|Allele List at MGI|
|Other mutations in this stock||
|Other mutations in Sacs||
|Nature of Mutation|
DNA sequencing using the SOLiD technique identified a T to C transition at position 12470 of the Sacs transcript using Ensembl record ENSMUST00000119943 in exon 9 of 9 total exons. Multiple transcripts of the Sacs gene are displayed on Ensembl. The mutated nucleotide causes a methionine to threonine substitution at amino acid 4157 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
|Protein Function & Prediction|
If using the Ensembl record ENSMUST00000119943, the Sacs gene encodes a 4582 amino acid protein sacsin that may function in chaperone-mediated protein folding, and contains one protein-interacting J domain at residues 4309-4396 and one nucleotide-binding HEPN domain at residues 4454-4570 (Uniprot Q9JLC8). The NCBI record NM_172809 predicts a 768 amino acid protein that is identical with the first 731 amino acids of the longer protein, but does not contain the residue altered in busy mice (Uniprot B2RRL5). Humans with mutations in the SACS gene develop an early-onset neurodegenerative disease, spastic ataxia of the Charlevoix-Saguenay type (OMIM #270550).
The M4157T change is predicted to be benign by the PolyPhen program.
|Posted On||May 04, 2010|