Mutagenetix > Incidental Mutation

Incidental Mutation 'R5405:Ins2'

428673

Institutional Source

Beutler Lab

Gene Symbol

Ins2

Ensembl Gene

ENSMUSG00000000215

Gene Name

insulin II

Synonyms

Mody, Mody4, InsII, Ins-2

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.301) question?

Stock #

R5405 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

142232393-142233463 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 142233134 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Histidine at position 46 (R46H)

Ref Sequence

ENSEMBL: ENSMUSP00000124643 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000000220] [ENSMUST00000105930] [ENSMUST00000105931] [ENSMUST00000105932] [ENSMUST00000105933] [ENSMUST00000105934] [ENSMUST00000125933] [ENSMUST00000162317] [ENSMUST00000210288]

AlphaFold

P01326

Predicted Effect

probably damaging
Transcript: ENSMUST00000000220
AA Change: R46H

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000000220
Gene: ENSMUSG00000000215
AA Change: R46H

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
IlGF	28	109	2.21e-35	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000105930
AA Change: R46H

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000101550
Gene: ENSMUSG00000000215
AA Change: R46H

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
IlGF	28	79	2.13e-5	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000105931
AA Change: R46H

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000101551
Gene: ENSMUSG00000000215
AA Change: R46H

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
IlGF	28	69	2.81e-5	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000105932
AA Change: R46H

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000101552
Gene: ENSMUSG00000000215
AA Change: R46H

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
IlGF	28	109	2.21e-35	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000105933
AA Change: R46H

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000101553
Gene: ENSMUSG00000000215
AA Change: R46H

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
IlGF	28	109	2.21e-35	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000105934
AA Change: R46H

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000101554
Gene: ENSMUSG00000000215
AA Change: R46H

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
IlGF	28	109	2.21e-35	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000125933
AA Change: R46H

PolyPhen 2 Score 0.954 (Sensitivity: 0.79; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000115147
Gene: ENSMUSG00000000215
AA Change: R46H

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
IlGF	28	70	6.3e-9	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000162317
AA Change: R46H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000124643
Gene: ENSMUSG00000000215
AA Change: R46H

Domain	Start	End	E-Value	Type
signal peptide	1	24	N/A	INTRINSIC
IlGF	28	97	1.32e-33	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000210288
AA Change: R46H

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

Coding Region Coverage

1x: 99.3%
3x: 98.5%
10x: 96.8%
20x: 94.1%

Validation Efficiency

MGI Phenotype

FUNCTION: This gene encodes insulin, a peptide hormone that plays a vital role in the regulation of carbohydrate and lipid metabolism. The encoded precursor protein undergoes proteolytic cleavage to produce a disulfide-linked heterodimeric functional protein that is stored in secretory granules. An increase in blood glucose levels, among others, induces the release of insulin from the secretory granules. Mice deficient in the functional hormone encoded by this gene develop diabetes mellitus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]
PHENOTYPE: Mice homozygous for spontaneous or knock-out alleles exhibit increased mortality, abnormal growth, abnormal glucose homeostasis, impaired pancreatic function, and phenotypes associated with type 2 diabetes. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 43 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Add2	A	T	6: 86,078,179 (GRCm39)	T298S	probably benign	Het
Atad2b	G	A	12: 4,990,098 (GRCm39)	R141Q	possibly damaging	Het
B3glct	A	G	5: 149,632,818 (GRCm39)	Q56R	probably damaging	Het
Cdc42bpa	A	G	1: 179,894,894 (GRCm39)	Y358C	probably damaging	Het
Cdc42bpa	A	G	1: 179,966,085 (GRCm39)	E1136G	possibly damaging	Het
Ceacam1	A	T	7: 25,163,290 (GRCm39)	N314K	probably benign	Het
Ces1g	A	T	8: 94,032,496 (GRCm39)	I488N	probably benign	Het
Chd6	C	T	2: 160,807,310 (GRCm39)	R1968K	probably benign	Het
Cyp27b1	C	T	10: 126,886,255 (GRCm39)	T312I	possibly damaging	Het
Cyp39a1	C	T	17: 43,987,831 (GRCm39)	A99V	probably damaging	Het
Dipk1a	C	T	5: 108,057,827 (GRCm39)	V199I	probably benign	Het
Dnaaf9	A	G	2: 130,554,380 (GRCm39)	S890P	probably damaging	Het
Efcab3	A	T	11: 104,612,018 (GRCm39)	D620V	probably benign	Het
Elapor1	A	T	3: 108,375,102 (GRCm39)	C588*	probably null	Het
Erc1	A	T	6: 119,801,905 (GRCm39)	S37R	probably damaging	Het
Gm10801	TC	TCGAC	2: 98,494,151 (GRCm39)		probably benign	Het
Gm14443	T	C	2: 175,013,644 (GRCm39)	I43V	possibly damaging	Het
Krt77	T	C	15: 101,769,523 (GRCm39)	I413V	probably damaging	Het
Lpin3	A	G	2: 160,745,849 (GRCm39)	D660G	probably damaging	Het
Mpp3	T	C	11: 101,901,047 (GRCm39)	Q318R	probably benign	Het
Mpzl2	T	C	9: 44,958,503 (GRCm39)	S80P	probably damaging	Het
Mrpl2	T	C	17: 46,960,036 (GRCm39)		probably null	Het
Mrpl48	T	C	7: 100,209,000 (GRCm39)	Y108C	probably damaging	Het
Ndufaf7	C	A	17: 79,246,044 (GRCm39)	F92L	probably damaging	Het
Or14c43	T	C	7: 86,115,383 (GRCm39)	Y255H	probably damaging	Het
Or6c8	T	A	10: 128,915,265 (GRCm39)	D189V	probably damaging	Het
Rec114	T	C	9: 58,567,624 (GRCm39)	S121G	probably benign	Het
Rnase10	A	T	14: 51,247,317 (GRCm39)	I195F	probably damaging	Het
Rnd2	C	T	11: 101,359,825 (GRCm39)	L57F	probably damaging	Het
Rreb1	A	G	13: 38,133,087 (GRCm39)	E1754G	probably damaging	Het
Sec31a	G	T	5: 100,531,657 (GRCm39)	C238*	probably null	Het
Slc12a6	T	C	2: 112,169,724 (GRCm39)	V337A	probably damaging	Het
Slc25a37	A	G	14: 69,482,344 (GRCm39)	V319A	possibly damaging	Het
Slc26a10	T	C	10: 127,010,864 (GRCm39)	Y456C	probably benign	Het
Slc27a3	G	A	3: 90,294,382 (GRCm39)	T463I	probably benign	Het
Slc66a3	A	G	12: 17,043,315 (GRCm39)		probably benign	Het
Stard9	T	A	2: 120,524,149 (GRCm39)	D781E	probably benign	Het
Tle1	T	C	4: 72,057,208 (GRCm39)		probably benign	Het
Tmem229b-ps	T	C	10: 53,351,325 (GRCm39)		noncoding transcript	Het
Vmn2r114	ATTT	ATT	17: 23,509,906 (GRCm39)		probably null	Het
Vmn2r71	A	G	7: 85,268,622 (GRCm39)	D275G	probably benign	Het
Wdr1	T	C	5: 38,692,543 (GRCm39)	T121A	probably benign	Het
Zdhhc19	C	T	16: 32,325,869 (GRCm39)	R240C	possibly damaging	Het

Other mutations in Ins2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01902:Ins2	APN	7	142,233,179 (GRCm39)	missense	probably damaging	1.00
R6125:Ins2	UTSW	7	142,233,430 (GRCm39)	splice site	probably null
R7766:Ins2	UTSW	7	142,232,494 (GRCm39)	missense	probably benign	0.36
R7814:Ins2	UTSW	7	142,233,323 (GRCm39)	intron	probably benign
R8064:Ins2	UTSW	7	142,232,553 (GRCm39)	missense	probably benign	0.04
R9151:Ins2	UTSW	7	142,232,505 (GRCm39)	missense	possibly damaging	0.89
R9760:Ins2	UTSW	7	142,233,185 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GGCAGGATTCTTACTCATTCCTGG -3'
(R):5'- AACCCAGCCTATCTTCCAGG -3'

Sequencing Primer
(F):5'- GCAGCTGCCATGTTTACATATG -3'
(R):5'- AGGTTATTGTTTCAACATGGCCC -3'

Posted On

2016-09-06