Incidental Mutation '2107:Wfs1'
ID |
146 |
Institutional Source |
Beutler Lab
|
Gene Symbol |
Wfs1
|
Ensembl Gene |
ENSMUSG00000039474 |
Gene Name |
wolframin ER transmembrane glycoprotein |
Synonyms |
wolframin, Wolfram syndrome 1 homolog (human) |
Accession Numbers |
|
Essential gene? |
Possibly essential
(E-score: 0.506)
|
Stock # |
2107
of strain
triaka
|
Quality Score |
|
Status
|
Validated
|
Chromosome |
5 |
Chromosomal Location |
37123448-37146326 bp(-) (GRCm39) |
Type of Mutation |
missense |
DNA Base Change (assembly) |
C to T
at 37124617 bp (GRCm39)
|
Zygosity |
Heterozygous |
Amino Acid Change |
Arginine to Histidine
at position 758
(R758H)
|
Ref Sequence |
ENSEMBL: ENSMUSP00000048053
(fasta)
|
Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000043964]
[ENSMUST00000166339]
|
AlphaFold |
P56695 |
Predicted Effect |
probably damaging
Transcript: ENSMUST00000043964
AA Change: R758H
PolyPhen 2
Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
|
SMART Domains |
Protein: ENSMUSP00000048053 Gene: ENSMUSG00000039474 AA Change: R758H
Domain | Start | End | E-Value | Type |
low complexity region
|
6 |
23 |
N/A |
INTRINSIC |
low complexity region
|
50 |
67 |
N/A |
INTRINSIC |
Blast:SEL1
|
101 |
139 |
1e-8 |
BLAST |
low complexity region
|
268 |
275 |
N/A |
INTRINSIC |
transmembrane domain
|
313 |
335 |
N/A |
INTRINSIC |
transmembrane domain
|
342 |
364 |
N/A |
INTRINSIC |
transmembrane domain
|
407 |
424 |
N/A |
INTRINSIC |
transmembrane domain
|
431 |
453 |
N/A |
INTRINSIC |
transmembrane domain
|
495 |
517 |
N/A |
INTRINSIC |
transmembrane domain
|
529 |
551 |
N/A |
INTRINSIC |
transmembrane domain
|
561 |
583 |
N/A |
INTRINSIC |
transmembrane domain
|
590 |
612 |
N/A |
INTRINSIC |
transmembrane domain
|
632 |
654 |
N/A |
INTRINSIC |
low complexity region
|
877 |
886 |
N/A |
INTRINSIC |
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000166339
AA Change: R682H
PolyPhen 2
Score 0.002 (Sensitivity: 0.99; Specificity: 0.30)
|
SMART Domains |
Protein: ENSMUSP00000132404 Gene: ENSMUSG00000039474 AA Change: R682H
Domain | Start | End | E-Value | Type |
low complexity region
|
6 |
23 |
N/A |
INTRINSIC |
low complexity region
|
50 |
67 |
N/A |
INTRINSIC |
Blast:SEL1
|
101 |
139 |
3e-8 |
BLAST |
low complexity region
|
268 |
275 |
N/A |
INTRINSIC |
low complexity region
|
334 |
345 |
N/A |
INTRINSIC |
transmembrane domain
|
419 |
441 |
N/A |
INTRINSIC |
transmembrane domain
|
453 |
475 |
N/A |
INTRINSIC |
transmembrane domain
|
485 |
507 |
N/A |
INTRINSIC |
transmembrane domain
|
514 |
536 |
N/A |
INTRINSIC |
transmembrane domain
|
556 |
578 |
N/A |
INTRINSIC |
low complexity region
|
801 |
810 |
N/A |
INTRINSIC |
|
Predicted Effect |
probably benign
Transcript: ENSMUST00000167937
|
SMART Domains |
Protein: ENSMUSP00000125779 Gene: ENSMUSG00000039474
Domain | Start | End | E-Value | Type |
Blast:SEL1
|
20 |
58 |
4e-9 |
BLAST |
|
Meta Mutation Damage Score |
0.2672 |
Coding Region Coverage |
|
Validation Efficiency |
80% (79/99) |
MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a transmembrane protein, which is located primarily in the endoplasmic reticulum and ubiquitously expressed with highest levels in brain, pancreas, heart, and insulinoma beta-cell lines. Mutations in this gene are associated with Wolfram syndrome, also called DIDMOAD (Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, and Deafness), an autosomal recessive disorder. The disease affects the brain and central nervous system. Mutations in this gene can also cause autosomal dominant deafness 6 (DFNA6), also known as DFNA14 or DFNA38. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2009] PHENOTYPE: Mice homozygous for a null allele exhibit decreased pancreatic beta cells and impaired glucose tolerance. Mice homozygous for a knock-out allele exhibit impaired glucose tolerance, decreased body weight, and abnormal behavior associated with increased sensitivity to stress. [provided by MGI curators]
|
Allele List at MGI |
All alleles(5) : Targeted, knock-out(1) Targeted, other(3) Gene trapped(1) |
Other mutations in this stock |
Total: 6 list
Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
Afmid |
T |
A |
11: 117,726,387 (GRCm39) |
N198K |
probably damaging |
Homo |
Fam184a |
T |
C |
10: 53,517,153 (GRCm39) |
E374G |
probably damaging |
Homo |
Mypn |
C |
T |
10: 63,039,530 (GRCm39) |
|
probably benign |
Homo |
Nme7 |
T |
A |
1: 164,172,922 (GRCm39) |
I211N |
possibly damaging |
Het |
Tmod4 |
G |
A |
3: 95,037,479 (GRCm39) |
|
probably null |
Homo |
Zfp112 |
T |
C |
7: 23,826,266 (GRCm39) |
C745R |
probably damaging |
Het |
|
Other mutations in Wfs1 |
Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
IGL01023:Wfs1
|
APN |
5 |
37,125,261 (GRCm39) |
nonsense |
probably null |
|
IGL01391:Wfs1
|
APN |
5 |
37,128,907 (GRCm39) |
missense |
probably benign |
0.10 |
IGL01788:Wfs1
|
APN |
5 |
37,125,980 (GRCm39) |
missense |
probably benign |
0.01 |
IGL02169:Wfs1
|
APN |
5 |
37,125,823 (GRCm39) |
missense |
probably damaging |
0.99 |
IGL02814:Wfs1
|
APN |
5 |
37,125,013 (GRCm39) |
missense |
possibly damaging |
0.88 |
IGL03294:Wfs1
|
APN |
5 |
37,132,941 (GRCm39) |
missense |
probably damaging |
1.00 |
IGL03299:Wfs1
|
APN |
5 |
37,125,731 (GRCm39) |
nonsense |
probably null |
|
R0077:Wfs1
|
UTSW |
5 |
37,130,538 (GRCm39) |
missense |
probably damaging |
1.00 |
R0180:Wfs1
|
UTSW |
5 |
37,124,372 (GRCm39) |
missense |
probably damaging |
0.96 |
R0402:Wfs1
|
UTSW |
5 |
37,134,324 (GRCm39) |
unclassified |
probably benign |
|
R0458:Wfs1
|
UTSW |
5 |
37,126,013 (GRCm39) |
missense |
probably damaging |
0.98 |
R0533:Wfs1
|
UTSW |
5 |
37,131,066 (GRCm39) |
splice site |
probably benign |
|
R0890:Wfs1
|
UTSW |
5 |
37,132,888 (GRCm39) |
missense |
probably damaging |
1.00 |
R0948:Wfs1
|
UTSW |
5 |
37,124,905 (GRCm39) |
missense |
probably damaging |
1.00 |
R1413:Wfs1
|
UTSW |
5 |
37,139,422 (GRCm39) |
missense |
possibly damaging |
0.65 |
R1759:Wfs1
|
UTSW |
5 |
37,124,359 (GRCm39) |
missense |
probably damaging |
0.99 |
R2009:Wfs1
|
UTSW |
5 |
37,125,653 (GRCm39) |
missense |
probably damaging |
0.96 |
R2137:Wfs1
|
UTSW |
5 |
37,124,845 (GRCm39) |
missense |
probably damaging |
0.99 |
R2157:Wfs1
|
UTSW |
5 |
37,125,286 (GRCm39) |
missense |
probably damaging |
1.00 |
R2216:Wfs1
|
UTSW |
5 |
37,124,564 (GRCm39) |
nonsense |
probably null |
|
R3779:Wfs1
|
UTSW |
5 |
37,125,968 (GRCm39) |
missense |
probably benign |
0.01 |
R3850:Wfs1
|
UTSW |
5 |
37,125,968 (GRCm39) |
missense |
probably benign |
0.01 |
R3853:Wfs1
|
UTSW |
5 |
37,125,968 (GRCm39) |
missense |
probably benign |
0.01 |
R3918:Wfs1
|
UTSW |
5 |
37,125,968 (GRCm39) |
missense |
probably benign |
0.01 |
R4093:Wfs1
|
UTSW |
5 |
37,124,809 (GRCm39) |
missense |
probably damaging |
0.97 |
R5056:Wfs1
|
UTSW |
5 |
37,132,931 (GRCm39) |
missense |
probably benign |
0.00 |
R5849:Wfs1
|
UTSW |
5 |
37,130,608 (GRCm39) |
missense |
probably damaging |
1.00 |
R5997:Wfs1
|
UTSW |
5 |
37,125,094 (GRCm39) |
missense |
probably damaging |
0.99 |
R6666:Wfs1
|
UTSW |
5 |
37,124,963 (GRCm39) |
missense |
possibly damaging |
0.94 |
R7024:Wfs1
|
UTSW |
5 |
37,124,294 (GRCm39) |
missense |
probably damaging |
1.00 |
R7157:Wfs1
|
UTSW |
5 |
37,124,516 (GRCm39) |
missense |
probably benign |
0.00 |
R7264:Wfs1
|
UTSW |
5 |
37,125,190 (GRCm39) |
missense |
probably damaging |
1.00 |
R7269:Wfs1
|
UTSW |
5 |
37,125,134 (GRCm39) |
nonsense |
probably null |
|
R7365:Wfs1
|
UTSW |
5 |
37,125,076 (GRCm39) |
missense |
probably benign |
0.33 |
R7657:Wfs1
|
UTSW |
5 |
37,125,578 (GRCm39) |
missense |
probably benign |
0.01 |
R8422:Wfs1
|
UTSW |
5 |
37,131,219 (GRCm39) |
missense |
probably benign |
0.17 |
R8427:Wfs1
|
UTSW |
5 |
37,125,431 (GRCm39) |
missense |
probably damaging |
1.00 |
R8446:Wfs1
|
UTSW |
5 |
37,128,953 (GRCm39) |
missense |
probably benign |
0.00 |
R8949:Wfs1
|
UTSW |
5 |
37,124,287 (GRCm39) |
missense |
probably damaging |
0.99 |
R9673:Wfs1
|
UTSW |
5 |
37,125,113 (GRCm39) |
missense |
probably damaging |
0.99 |
|
Nature of Mutation |
DNA sequencing using the SOLiD technique identified a G to A transition at position 2395 of the Wfs1 transcript in exon 8 of 8 total exons. The mutated nucleotide causes an arginine to histidine substitution at amino acid 758 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
|
Protein Function and Prediction |
The Wfs1 gene encodes an 890 amino acid protein known as Wolframin. Wolframin is a multi-pass endoplasmic reticulum (ER) membrane protein that participates in the regulation of cellular Ca 2+ homeostasis, at least partly, by modulating the filling state of the endoplasmic reticulum Ca 2+ store (Uniprot P56695). Mice homozygous for a null allele exhibit decreased numbers of pancreatic beta cells and impaired glucose tolerance. Mice homozygous for another knock-out allele exhibit impaired glucose tolerance, decreased body weight, and abnormal behavior associated with increased sensitivity to stress.
The R758H change is predicted to be possibly damaging by the PolyPhen program.
|
Posted On |
2010-03-19 |