Mutagenetix > Incidental Mutation

Incidental Mutation 'N/A - 287:Fndc5'

167

Institutional Source

Beutler Lab

Gene Symbol

Fndc5

Ensembl Gene

ENSMUSG00000001334

Gene Name

fibronectin type III domain containing 5

Synonyms

Pxp, 1500001L03Rik, PeP

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.098) question?

Stock #

N/A - 287 of strain 287

Quality Score

Status

Validated

Chromosome

Chromosomal Location

129030792-129038386 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 129033142 bp (GRCm39)

Zygosity

Homozygous

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]

AlphaFold

Q8K4Z2

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

Domain	Start	End	E-Value	Type
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

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
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Fbxo10	G	A	4: 45,044,708 (GRCm39)		probably benign	Het
Pkhd1l1	A	G	15: 44,445,654 (GRCm39)	T3779A	probably damaging	Het
Sorl1	A	T	9: 41,952,892 (GRCm39)	C716*	probably null	Homo

Other mutations in Fndc5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02656:Fndc5	APN	4	129,033,239 (GRCm39)	missense	probably damaging	1.00
IGL03336:Fndc5	APN	4	129,033,711 (GRCm39)	missense	probably benign	0.00
R0645:Fndc5	UTSW	4	129,033,630 (GRCm39)	splice site	probably benign
R1202:Fndc5	UTSW	4	129,033,238 (GRCm39)	missense	probably damaging	0.97
R3962:Fndc5	UTSW	4	129,033,688 (GRCm39)	missense	probably benign	0.23
R4408:Fndc5	UTSW	4	129,036,322 (GRCm39)	splice site	probably null
R5379:Fndc5	UTSW	4	129,035,887 (GRCm39)	missense	probably damaging	1.00
R5539:Fndc5	UTSW	4	129,032,514 (GRCm39)	missense	probably damaging	1.00
R6242:Fndc5	UTSW	4	129,033,688 (GRCm39)	missense	probably benign	0.23
R6951:Fndc5	UTSW	4	129,032,573 (GRCm39)	missense	possibly damaging	0.77
R7027:Fndc5	UTSW	4	129,033,316 (GRCm39)	missense	probably benign	0.00
R7112:Fndc5	UTSW	4	129,035,915 (GRCm39)	missense	probably benign	0.09
R8254:Fndc5	UTSW	4	129,032,514 (GRCm39)	missense	possibly damaging	0.86
R8947:Fndc5	UTSW	4	129,030,929 (GRCm39)	missense	probably benign	0.04
RF014:Fndc5	UTSW	4	129,035,960 (GRCm39)	missense	probably benign	0.00
Z31818:Fndc5	UTSW	4	129,033,142 (GRCm39)	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 On

2010-04-08