Mutagenetix > Incidental Mutation

Incidental Mutation 'R0077:Wfs1'

19466

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

038364-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.506) question?

Stock #

R0077 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

37123448-37146326 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 37130538 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Isoleucine at position 236 (S236I)

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: S236I

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000048053
Gene: ENSMUSG00000039474
AA Change: S236I

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: S236I

PolyPhen 2 Score 0.975 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000132404
Gene: ENSMUSG00000039474
AA Change: S236I

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

unknown
Transcript: ENSMUST00000167937
AA Change: S154I

SMART Domains

Protein: ENSMUSP00000125779
Gene: ENSMUSG00000039474
AA Change: S154I

Domain	Start	End	E-Value	Type
Blast:SEL1	20	58	4e-9	BLAST

Meta Mutation Damage Score

0.4853

Coding Region Coverage

1x: 98.9%
3x: 97.9%
10x: 95.4%
20x: 90.5%

Validation Efficiency

83% (159/192)

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: 73 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adgrl3	T	C	5: 81,919,532 (GRCm39)		probably benign	Het
Adgrl4	A	G	3: 151,223,418 (GRCm39)	I624V	probably damaging	Het
AI661453	A	G	17: 47,780,287 (GRCm39)		probably benign	Het
Alg12	C	T	15: 88,700,181 (GRCm39)	E60K	probably damaging	Het
Angel2	A	T	1: 190,665,284 (GRCm39)	N72Y	possibly damaging	Het
Ank1	C	A	8: 23,630,183 (GRCm39)	P81Q	probably damaging	Het
Atp6v1c2	A	T	12: 17,371,613 (GRCm39)	D61E	probably damaging	Het
Bpi	T	A	2: 158,103,254 (GRCm39)	M83K	probably damaging	Het
Capn7	A	G	14: 31,090,072 (GRCm39)	I642V	probably benign	Het
Ccdc134	T	C	15: 82,015,938 (GRCm39)		probably benign	Het
Ccr3	C	T	9: 123,829,061 (GRCm39)	T132I	probably damaging	Het
Cfap65	C	A	1: 74,971,077 (GRCm39)	W80C	probably damaging	Het
Chaf1a	T	A	17: 56,354,384 (GRCm39)	I218K	unknown	Het
Ddx23	A	G	15: 98,554,481 (GRCm39)		probably null	Het
Dmkn	A	G	7: 30,464,719 (GRCm39)	S231G	probably benign	Het
Ep300	T	C	15: 81,525,514 (GRCm39)	I1446T	unknown	Het
Fmnl1	T	C	11: 103,080,795 (GRCm39)	F318S	probably damaging	Het
Grik5	A	T	7: 24,722,805 (GRCm39)	V497E	probably damaging	Het
Gtf2ird2	T	C	5: 134,242,925 (GRCm39)	Y380H	probably damaging	Het
Hecw2	C	T	1: 53,907,990 (GRCm39)		probably benign	Het
Hspb7	A	G	4: 141,151,358 (GRCm39)	I167V	probably damaging	Het
Kcnh2	T	A	5: 24,527,700 (GRCm39)	N884I	probably benign	Het
Krba1	T	C	6: 48,382,159 (GRCm39)		probably benign	Het
Krt18	G	T	15: 101,939,409 (GRCm39)	R294L	probably benign	Het
Lctl	T	A	9: 64,029,389 (GRCm39)	M1K	probably null	Het
Lingo2	G	A	4: 35,708,375 (GRCm39)	S535F	possibly damaging	Het
Lrba	A	C	3: 86,449,995 (GRCm39)	N2105H	probably damaging	Het
Lrrc10	A	G	10: 116,881,419 (GRCm39)	D31G	probably damaging	Het
Lrrtm1	T	A	6: 77,220,855 (GRCm39)	V104E	probably damaging	Het
Mgat3	C	T	15: 80,096,778 (GRCm39)	T535I	probably benign	Het
Nav3	T	C	10: 109,552,503 (GRCm39)	I1780V	possibly damaging	Het
Nlrc4	A	G	17: 74,753,826 (GRCm39)	W186R	probably damaging	Het
Nr2c1	T	A	10: 94,024,117 (GRCm39)	F441I	probably benign	Het
Obscn	A	G	11: 58,942,347 (GRCm39)		probably benign	Het
Or1p1	T	C	11: 74,179,501 (GRCm39)	F10L	probably benign	Het
Or2a56	T	C	6: 42,932,707 (GRCm39)	S92P	probably benign	Het
Or56b34	T	C	7: 104,937,726 (GRCm39)	V142A	probably damaging	Het
Or5au1	T	C	14: 52,273,442 (GRCm39)	N42S	possibly damaging	Het
Osr1	A	T	12: 9,629,691 (GRCm39)	Y188F	probably damaging	Het
Pak2	A	T	16: 31,852,661 (GRCm39)	N293K	possibly damaging	Het
Pappa	A	T	4: 65,226,049 (GRCm39)	T1301S	probably damaging	Het
Pde4dip	G	A	3: 97,660,442 (GRCm39)	Q679*	probably null	Het
Pik3r5	T	A	11: 68,377,448 (GRCm39)		probably null	Het
Plbd2	C	T	5: 120,624,104 (GRCm39)		probably null	Het
Ppp1r3a	G	T	6: 14,754,516 (GRCm39)	P244T	possibly damaging	Het
Pum1	C	A	4: 130,499,985 (GRCm39)	R960S	probably benign	Het
Ralgapb	T	C	2: 158,315,169 (GRCm39)	Y845H	probably damaging	Het
Rbms1	A	T	2: 60,589,179 (GRCm39)	M287K	possibly damaging	Het
Rdh1	A	T	10: 127,595,906 (GRCm39)	I34F	probably damaging	Het
Rgl3	T	A	9: 21,885,398 (GRCm39)	Q644L	probably benign	Het
Rpap2	T	C	5: 107,768,340 (GRCm39)	S393P	probably damaging	Het
Rsad2	T	C	12: 26,506,376 (GRCm39)	S15G	probably damaging	Het
Rspo1	G	A	4: 124,885,190 (GRCm39)	R22Q	probably benign	Het
S100a11	A	C	3: 93,431,509 (GRCm39)		probably null	Het
Septin4	T	C	11: 87,472,022 (GRCm39)	S11P	probably benign	Het
Serpina1c	T	C	12: 103,862,350 (GRCm39)	S322G	probably benign	Het
Setdb1	A	T	3: 95,248,762 (GRCm39)	C385S	probably damaging	Het
Shank2	A	T	7: 143,746,204 (GRCm39)	I193F	possibly damaging	Het
Slc4a11	G	T	2: 130,528,221 (GRCm39)		probably benign	Het
Snrnp40	C	G	4: 130,271,836 (GRCm39)		probably null	Het
Tbcd	C	A	11: 121,485,100 (GRCm39)	Q761K	probably benign	Het
Tmed6	C	T	8: 107,792,198 (GRCm39)	V16M	probably damaging	Het
Tmem229a	T	C	6: 24,955,701 (GRCm39)	T18A	probably benign	Het
Tsc1	T	A	2: 28,568,955 (GRCm39)		probably benign	Het
Ube2m	T	C	7: 12,769,657 (GRCm39)	N49D	probably damaging	Het
Ubqlnl	T	C	7: 103,799,254 (GRCm39)	D81G	probably damaging	Het
Vmn2r56	A	G	7: 12,449,332 (GRCm39)	V302A	probably benign	Het
Vmn2r73	T	A	7: 85,525,075 (GRCm39)	R24S	probably benign	Het
Xpot	A	T	10: 121,441,544 (GRCm39)	N560K	probably benign	Het
Yipf3	A	G	17: 46,562,503 (GRCm39)	T303A	probably benign	Het
Zfp790	T	C	7: 29,524,300 (GRCm39)	W19R	probably damaging	Het
Zfp846	T	C	9: 20,505,303 (GRCm39)	C388R	probably benign	Het
Zpr1	T	A	9: 46,184,634 (GRCm39)	I47N	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
2107:Wfs1	UTSW	5	37,124,617 (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

Predicted Primers

PCR Primer
(F):5'- TGACCTTTCAGCTCACTCAGGCAC -3'
(R):5'- TCACGGAACATGCTGACACTCCTC -3'

Sequencing Primer
(F):5'- TCCCAGTGTACAAAGGCTTAG -3'
(R):5'- CCATGTGATTCCTGAGAACAGTG -3'

Posted On

2013-04-11