Incidental Mutation 'F5493:Frrs1l'

• ID: 566
• Institutional Source: Beutler Lab
• Gene Symbol: Frrs1l
• Ensembl Gene: ENSMUSG00000045589
• Gene Name: ferric-chelate reductase 1 like
• Synonyms: 6430704M03Rik
• Essential gene?: Possibly non essential (E-score: 0.425)
• Stock #: F5493 (G1)
• Status: Validated
• Chromosome: 4
• Chromosomal Location: 56960136-56990391 bp(-) (GRCm39)
• Type of Mutation: missense
• DNA Base Change (assembly): T to C at 56968293 bp (GRCm39)
• Zygosity: Heterozygous
• Amino Acid Change: Methionine to Valine at position 160 (M160V)
• Ref Sequence: ENSEMBL: ENSMUSP00000052507
• Gene Model: predicted gene model for transcript(s): [ENSMUST00000053681] [ENSMUST00000128276]
• AlphaFold: B1AXV0
• Predicted Effect: probably benign; Transcript: ENSMUST00000053681; AA Change: M160V; PolyPhen 2 Score 0.130 (Sensitivity: 0.93; Specificity: 0.86)
• SMART Domains: Protein: ENSMUSP00000052507; Gene: ENSMUSG00000045589; AA Change: M160V

Domain	Start	End	E-Value	Type
signal peptide	1	28	N/A	INTRINSIC
DoH	143	232	1.96e-10	SMART
transmembrane domain	267	289	N/A	INTRINSIC

• Predicted Effect: probably benign; Transcript: ENSMUST00000128276
• Meta Mutation Damage Score: 0.2123
• Coding Region Coverage:
  • 1x: 76.6%
  • 3x: 51.4%
• Het Detection Efficiency: 27.8%
• Validation Efficiency: 67% (74/111)
• MGI Phenotype: FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a component of the outer-core of an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor protein in the brain. The encoded protein is thought to interact with inner-core components of the receptor, and play a role in the modulation of glutamate signaling. Mutations in this gene are associated with early infantile epileptic encephalopathy 37. [provided by RefSeq, Jul 2016]
• Allele List at MGI:

  All alleles(8) : Gene trapped(8)

• Posted On: 2010-11-29

Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to G transition at position 598 of the 6430704M03Riktranscript in exon 4 of 5 total exons.  Multiple transcripts of the 6430704M03Rikgene are displayed on Ensembl and Vega. The mutated nucleotide causes a methionine to valine substitution at amino acid 160 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (see related file).

Protein Function and Prediction

The 6430704M03Rik gene is predicted to encode a 293 amino acid protein. SMART analysis indicates a signal peptide at amino acids 1-28 and a DoH or DOMON domain at amino acids 118-261. This predominantly beta-sheet domain is typically found in as a regulatory N-terminal domain in dopamine beta-monooxygenase and and in several other secreted and transmembrane proteins. A C-terminal transmembrane domain is located at residues 267-289.

The M160V change is located in the DoH domain, and is predicted to be possibly damaging by the PolyPhen program.