Incidental Mutation 'N/A - 287:Fndc5'
ID167
Institutional Source Beutler Lab
Gene Symbol Fndc5
Ensembl Gene ENSMUSG00000001334
Gene Namefibronectin type III domain containing 5
Synonyms1500001L03Rik, PeP, Pxp
Accession Numbers

Genbank: NM_027402; MGI: 1917614  

Is this an essential gene? Probably non essential (E-score: 0.104) question?
Stock #N/A - 287 of strain 287
Quality Score
Status Validated
Chromosome4
Chromosomal Location129136999-129144593 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) G to A at 129139349 bp
ZygosityHomozygous
Amino Acid Change Aspartic acid to Asparagine at position 70 (D70N)
Ref Sequence ENSEMBL: ENSMUSP00000099660 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000102600]
Predicted Effect probably damaging
Transcript: ENSMUST00000102600
AA Change: D70N

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)
SMART Domains Protein: ENSMUSP00000099660
Gene: ENSMUSG00000001334
AA Change: D70N

DomainStartEndE-ValueType
FN3 31 111 7.34e-9 SMART
Pfam:DUF4808 146 204 4.7e-10 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000124746
Meta Mutation Damage Score 0.1699 question?
Coding Region Coverage
  • 1x: 88.3%
  • 3x: 72.3%
Validation Efficiency 81% (138/170)
MGI Phenotype FUNCTION: This gene encodes a type I transmembrane protein containing fibronectin type III repeat. The encoded transmembrane protein undergoes proteolytic processing to generate a soluble hormone named irisin that is secreted into the bloodstream. The expression of this gene followed by the secretion of irisin from skeletal muscle is induced by exercise. The ectopic expression of the encoded protein in mice causes an elevation of irisin in blood and improves metabolic health. [provided by RefSeq, Jul 2016]
Allele List at MGI

All alleles(1) : Gene trapped(1)

Other mutations in this stock
Total: 3 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Fbxo10 G A 4: 45,044,708 probably benign Het
Pkhd1l1 A G 15: 44,582,258 T3779A probably damaging Het
Sorl1 A T 9: 42,041,596 C716* probably null Homo
Other mutations in Fndc5
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02656:Fndc5 APN 4 129139446 missense probably damaging 1.00
IGL03336:Fndc5 APN 4 129139918 missense probably benign 0.00
R0645:Fndc5 UTSW 4 129139837 splice site probably benign
R1202:Fndc5 UTSW 4 129139445 missense probably damaging 0.97
R3962:Fndc5 UTSW 4 129139895 missense probably benign 0.23
R4408:Fndc5 UTSW 4 129142529 splice site probably null
R5379:Fndc5 UTSW 4 129142094 missense probably damaging 1.00
R5539:Fndc5 UTSW 4 129138721 missense probably damaging 1.00
R6242:Fndc5 UTSW 4 129139895 missense probably benign 0.23
R6951:Fndc5 UTSW 4 129138780 missense possibly damaging 0.77
R7027:Fndc5 UTSW 4 129139523 missense probably benign 0.00
R7112:Fndc5 UTSW 4 129142122 missense probably benign 0.09
R8254:Fndc5 UTSW 4 129138721 missense possibly damaging 0.86
RF014:Fndc5 UTSW 4 129142167 missense probably benign 0.00
Z31818:Fndc5 UTSW 4 129139349 missense probably damaging 1.00
Nature of Mutation

DNA sequencing using the SOLiD technique identified a G to A transition at position 227 of the Fndc5 transcript in exon 3 of 6 total exons.  The mutated nucleotide causes an aspartic acid to asparagine substitution at amino acid 70 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

 
Protein Function and Prediction
The Fndc5 gene encodes a 209 amino acid single-pass type I membrane protein that is localized to peroxisome membranes. It is highly expressed in skeletal muscle, heart and brain, and is detected mostly in skeletal muscle during embryonic development. The protein contains one extracellular fibronectin type III domain at amino acids 31-121. A peroxisome targeting motif is present at amino acids 207-209 (Uniprot Q8K4Z2).
 
The D70N change occurs in the fibronectin type III domain, and is predicted to be benign by the PolyPhen program.
Posted On2010-04-08