Mutagenetix > Incidental Mutation

Incidental Mutation 'R2157:Wfs1'

234896

Institutional Source

Beutler Lab

Gene Symbol

Wfs1

Ensembl Gene

ENSMUSG00000039474

Gene Name

wolframin ER transmembrane glycoprotein

Synonyms

wolframin, Wolfram syndrome 1 homolog (human)

MMRRC Submission

040160-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.506) question?

Stock #

R2157 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

37123448-37146326 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 37125286 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Proline to Leucine at position 535 (P535L)

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: P535L

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000048053
Gene: ENSMUSG00000039474
AA Change: P535L

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 damaging
Transcript: ENSMUST00000166339
AA Change: P459L

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000132404
Gene: ENSMUSG00000039474
AA Change: P459L

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

0.9391

Coding Region Coverage

1x: 99.2%
3x: 98.7%
10x: 97.5%
20x: 95.7%

Validation Efficiency

100% (80/80)

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: 83 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310022B05Rik	A	T	8: 125,378,168 (GRCm39)		probably benign	Het
4930590J08Rik	T	A	6: 91,919,468 (GRCm39)	M709K	possibly damaging	Het
4930590J08Rik	A	G	6: 91,894,679 (GRCm39)		probably null	Het
A930011G23Rik	T	G	5: 99,379,956 (GRCm39)	I394L	probably damaging	Het
Abca13	A	C	11: 9,527,170 (GRCm39)	M4528L	probably damaging	Het
Abcb1b	G	A	5: 8,874,791 (GRCm39)	A484T	probably benign	Het
Actn1	A	T	12: 80,219,891 (GRCm39)	M660K	probably benign	Het
Adgra3	G	T	5: 50,159,283 (GRCm39)	N322K	possibly damaging	Het
Ahnak	A	G	19: 8,978,048 (GRCm39)	I56V	possibly damaging	Het
Amotl2	A	G	9: 102,607,788 (GRCm39)		probably benign	Het
Apoa1	T	C	9: 46,140,471 (GRCm39)	V34A	probably damaging	Het
Arrdc1	G	A	2: 24,816,987 (GRCm39)	A113V	probably damaging	Het
As3mt	A	G	19: 46,696,231 (GRCm39)	D13G	probably benign	Het
Cald1	A	G	6: 34,662,976 (GRCm39)	Q13R	possibly damaging	Het
Ccdc28a	G	A	10: 18,106,203 (GRCm39)	T41I	probably benign	Het
Ccdc30	A	T	4: 119,190,921 (GRCm39)		probably benign	Het
Cct2	T	C	10: 116,898,714 (GRCm39)		probably benign	Het
Cdh12	T	C	15: 21,583,873 (GRCm39)	I571T	possibly damaging	Het
Cdh15	G	A	8: 123,588,763 (GRCm39)	R279Q	probably damaging	Het
Ckm	T	C	7: 19,155,279 (GRCm39)	S372P	probably benign	Het
Comp	C	T	8: 70,832,220 (GRCm39)	Q554*	probably null	Het
Csf2ra	T	C	19: 61,215,509 (GRCm39)	T70A	probably benign	Het
Csmd3	T	C	15: 47,559,183 (GRCm39)	E2256G	probably damaging	Het
Dicer1	A	T	12: 104,669,208 (GRCm39)	V1158D	probably benign	Het
Dner	A	G	1: 84,361,659 (GRCm39)	F650S	possibly damaging	Het
Dnm3	T	C	1: 162,135,462 (GRCm39)	N437S	possibly damaging	Het
Dpy19l2	T	C	9: 24,592,076 (GRCm39)	I176V	probably benign	Het
Dpy19l2	A	T	9: 24,495,928 (GRCm39)	C597S	probably benign	Het
Edf1	T	C	2: 25,448,043 (GRCm39)		probably null	Het
Eif1ad16	A	T	12: 87,985,481 (GRCm39)	S21T	unknown	Het
Enpp3	A	G	10: 24,652,776 (GRCm39)	F727S	probably damaging	Het
Epb42	C	T	2: 120,852,243 (GRCm39)	M583I	probably benign	Het
Foxred1	A	G	9: 35,116,659 (GRCm39)	F117S	probably damaging	Het
Fstl5	T	A	3: 76,615,372 (GRCm39)	M811K	possibly damaging	Het
Gm5117	A	T	8: 32,228,222 (GRCm39)		noncoding transcript	Het
Gpm6a	T	C	8: 55,511,833 (GRCm39)	S236P	probably damaging	Het
Grik1	G	A	16: 87,853,012 (GRCm39)	A57V	probably damaging	Het
Hdgfl2	G	A	17: 56,405,691 (GRCm39)	V476I	possibly damaging	Het
Il17b	G	T	18: 61,823,439 (GRCm39)	W91L	probably damaging	Het
Jph4	C	A	14: 55,350,984 (GRCm39)	R344L	probably benign	Het
Map3k21	A	G	8: 126,664,005 (GRCm39)	D522G	probably benign	Het
Mast2	A	G	4: 116,179,480 (GRCm39)	L398S	probably damaging	Het
Mbtd1	A	G	11: 93,801,214 (GRCm39)	T132A	probably benign	Het
Mbtps1	G	T	8: 120,269,466 (GRCm39)	T208K	probably benign	Het
Mr1	A	G	1: 155,022,376 (GRCm39)		probably null	Het
Mthfsd	G	A	8: 121,828,240 (GRCm39)	L140F	probably damaging	Het
Mybpc2	C	G	7: 44,159,269 (GRCm39)	D594H	possibly damaging	Het
Nalcn	T	C	14: 123,647,164 (GRCm39)	M570V	probably benign	Het
Ncam2	T	C	16: 81,287,277 (GRCm39)	I397T	probably damaging	Het
Ndufs4	C	T	13: 114,453,514 (GRCm39)	V75I	probably damaging	Het
Nek4	T	A	14: 30,701,925 (GRCm39)		probably null	Het
Nfatc1	G	T	18: 80,679,060 (GRCm39)	A762D	possibly damaging	Het
Nhsl3	C	T	4: 129,117,917 (GRCm39)	R249H	possibly damaging	Het
Npc1	A	G	18: 12,324,866 (GRCm39)	I1209T	probably damaging	Het
Or10k2	T	C	8: 84,268,250 (GRCm39)	I159T	probably benign	Het
Or4c11	A	T	2: 88,695,213 (GRCm39)	N88I	probably benign	Het
Pak5	T	C	2: 135,942,877 (GRCm39)	D421G	probably damaging	Het
Pias1	A	G	9: 62,820,112 (GRCm39)	V285A	possibly damaging	Het
Pigg	T	A	5: 108,466,755 (GRCm39)	I212N	probably damaging	Het
Plcd3	A	T	11: 102,961,974 (GRCm39)	C711S	probably benign	Het
Plscr5	G	A	9: 92,080,550 (GRCm39)	R12K	probably benign	Het
Plxna4	T	C	6: 32,493,909 (GRCm39)	I236V	probably benign	Het
Ppp1r26	T	C	2: 28,342,370 (GRCm39)	F667L	probably benign	Het
Prkx	A	G	X: 76,814,920 (GRCm39)	F247L	probably benign	Het
Qpct	G	A	17: 79,378,115 (GRCm39)	R95Q	probably benign	Het
Ralgapb	G	T	2: 158,279,392 (GRCm39)	M159I	probably benign	Het
Rnf145	T	C	11: 44,445,997 (GRCm39)	L277P	probably damaging	Het
Scn9a	A	G	2: 66,366,669 (GRCm39)	S705P	probably damaging	Het
Slc4a8	A	G	15: 100,704,254 (GRCm39)	T750A	probably damaging	Het
Slc66a1	A	T	4: 139,029,166 (GRCm39)	V106D	probably damaging	Het
Syne2	A	G	12: 76,141,230 (GRCm39)	E6114G	probably damaging	Het
Tat	T	C	8: 110,724,236 (GRCm39)	M375T	probably damaging	Het
Tex10	C	T	4: 48,436,522 (GRCm39)		probably benign	Het
Tmprss11e	T	C	5: 86,861,587 (GRCm39)	K320E	probably benign	Het
Tnr	T	C	1: 159,685,840 (GRCm39)	I357T	probably damaging	Het
Vmn1r229	A	T	17: 21,035,638 (GRCm39)	R294S	possibly damaging	Het
Vmn2r116	G	A	17: 23,620,443 (GRCm39)	D726N	probably damaging	Het
Vpreb1b	T	A	16: 17,798,934 (GRCm39)	L140*	probably null	Het
Xdh	A	G	17: 74,229,532 (GRCm39)	L307P	probably damaging	Het
Zfp160	A	G	17: 21,241,090 (GRCm39)	S53G	probably benign	Het
Zfp319	A	G	8: 96,054,659 (GRCm39)	C515R	probably damaging	Het
Zfp747	A	G	7: 126,974,929 (GRCm39)	F24L	possibly damaging	Het
Zzef1	A	T	11: 72,739,460 (GRCm39)		probably benign	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
2107:Wfs1	UTSW	5	37,124,617 (GRCm39)	missense	probably damaging	1.00
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
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

Predicted Primers

PCR Primer
(F):5'- AGGAACCATCGGGCAAACTG -3'
(R):5'- TCTGCTGAGCCCTATACCAG -3'

Sequencing Primer
(F):5'- TGCACCGTGCCCATCAAG -3'
(R):5'- TGAGCCCTATACCAGGCGTG -3'

Posted On

2014-10-01