Mutagenetix > Incidental Mutation

Incidental Mutation 'R0147:Irs2'

22625

Institutional Source

Beutler Lab

Gene Symbol

Irs2

Ensembl Gene

ENSMUSG00000038894

Gene Name

insulin receptor substrate 2

Synonyms

Irs-2

MMRRC Submission

038431-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.579) question?

Stock #

R0147 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

11034681-11058458 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 11057568 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Lysine at position 288 (M288K)

Ref Sequence

ENSEMBL: ENSMUSP00000038514 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000040514]

AlphaFold

P81122

PDB Structure

Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB peptide [X-RAY DIFFRACTION]
Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB peptide and ATP [X-RAY DIFFRACTION]
Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB phosphopeptide [X-RAY DIFFRACTION]

Predicted Effect

probably damaging
Transcript: ENSMUST00000040514
AA Change: M288K

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

SMART Domains

Protein: ENSMUSP00000038514
Gene: ENSMUSG00000038894
AA Change: M288K

Domain	Start	End	E-Value	Type
low complexity region	2	18	N/A	INTRINSIC
low complexity region	19	28	N/A	INTRINSIC
PH	31	146	2.83e-13	SMART
IRS	191	293	4.98e-38	SMART
PTBI	191	293	2.24e-51	SMART
low complexity region	301	309	N/A	INTRINSIC
low complexity region	364	377	N/A	INTRINSIC
low complexity region	435	473	N/A	INTRINSIC
low complexity region	478	490	N/A	INTRINSIC
low complexity region	688	710	N/A	INTRINSIC
low complexity region	721	730	N/A	INTRINSIC
low complexity region	834	846	N/A	INTRINSIC
low complexity region	923	959	N/A	INTRINSIC
low complexity region	976	984	N/A	INTRINSIC
low complexity region	997	1028	N/A	INTRINSIC
low complexity region	1137	1154	N/A	INTRINSIC
low complexity region	1191	1208	N/A	INTRINSIC
low complexity region	1274	1296	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000180750

Meta Mutation Damage Score

0.7989

Coding Region Coverage

1x: 98.9%
3x: 98.0%
10x: 94.5%
20x: 86.1%

Validation Efficiency

67% (88/131)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes the insulin receptor substrate 2, a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, as well as by an interleukin 4 receptor-associated kinase in response to IL4 treatment. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous disruption of this gene results in type 2 diabetes due to insulin resistance and pancreatic beta cell dysfunction, causes defects in leptin action, energy balance, lipid homeostasis and vascular wound healing, and leads to female infertility due to hypothalamic and ovarian dysfunction. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 88 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A2m	T	C	6: 121,639,405 (GRCm39)		probably null	Het
Abtb2	A	G	2: 103,397,480 (GRCm39)	I137V	probably benign	Het
Ank1	T	A	8: 23,613,993 (GRCm39)	N1545K	probably damaging	Het
Arl6	T	C	16: 59,439,153 (GRCm39)		probably benign	Het
Avl9	T	A	6: 56,713,487 (GRCm39)	D248E	probably benign	Het
Becn1	T	C	11: 101,192,562 (GRCm39)	E40G	probably damaging	Het
Bod1l	G	T	5: 41,976,040 (GRCm39)	A1758E	possibly damaging	Het
Btbd16	C	T	7: 130,381,324 (GRCm39)	T19I	probably damaging	Het
Casc3	T	A	11: 98,713,325 (GRCm39)	N246K	possibly damaging	Het
Celf1	G	T	2: 90,835,035 (GRCm39)		probably benign	Het
Chrm3	G	T	13: 9,928,780 (GRCm39)	N85K	probably damaging	Het
Cluh	T	A	11: 74,556,764 (GRCm39)	Y935N	probably damaging	Het
Col1a2	G	A	6: 4,518,822 (GRCm39)		probably benign	Het
Col6a5	T	C	9: 105,802,993 (GRCm39)	D1324G	unknown	Het
Ctcfl	T	C	2: 172,960,340 (GRCm39)	D81G	possibly damaging	Het
D630003M21Rik	C	T	2: 158,044,987 (GRCm39)		probably benign	Het
Ddx39a	C	T	8: 84,449,105 (GRCm39)	R298C	possibly damaging	Het
Dnmt3b	T	G	2: 153,503,377 (GRCm39)	N9K	possibly damaging	Het
Dock8	T	C	19: 25,096,823 (GRCm39)	L577P	probably benign	Het
Drc1	A	T	5: 30,486,487 (GRCm39)	N13I	possibly damaging	Het
Eml4	T	A	17: 83,729,081 (GRCm39)	N85K	probably damaging	Het
Epb41l4a	T	C	18: 33,931,853 (GRCm39)	T581A	probably damaging	Het
Epha3	T	C	16: 63,433,307 (GRCm39)	D446G	possibly damaging	Het
Fam209	G	T	2: 172,315,900 (GRCm39)	G92C	probably damaging	Het
Fam98c	T	A	7: 28,852,146 (GRCm39)	R340*	probably null	Het
Fbxw10	T	G	11: 62,738,307 (GRCm39)		probably null	Het
Galr1	A	G	18: 82,423,695 (GRCm39)	L194P	probably benign	Het
Gar1	T	C	3: 129,623,122 (GRCm39)	H89R	probably damaging	Het
Gbp4	T	A	5: 105,267,362 (GRCm39)	Y519F	probably benign	Het
Gm28042	T	A	2: 119,866,944 (GRCm39)	S196T	probably benign	Het
Grid2	T	C	6: 64,510,571 (GRCm39)	Y734H	probably benign	Het
Grm6	T	A	11: 50,750,144 (GRCm39)	I466N	possibly damaging	Het
Hectd3	T	C	4: 116,854,237 (GRCm39)		probably benign	Het
Hpse2	A	C	19: 42,920,099 (GRCm39)		probably null	Het
Hspb7	T	C	4: 141,151,302 (GRCm39)	I148T	probably damaging	Het
Htr1d	C	A	4: 136,170,788 (GRCm39)	T339K	probably damaging	Het
Ip6k1	T	A	9: 107,923,093 (GRCm39)	D408E	probably damaging	Het
Kansl3	A	T	1: 36,392,897 (GRCm39)	C225S	probably damaging	Het
Knop1	C	A	7: 118,445,061 (GRCm39)	R301L	probably benign	Het
Lama5	T	C	2: 179,832,199 (GRCm39)	H1714R	probably benign	Het
Mettl14	G	A	3: 123,165,043 (GRCm39)	T316I	probably damaging	Het
Mmp15	A	T	8: 96,098,945 (GRCm39)	N591Y	probably benign	Het
Mprip	T	A	11: 59,627,899 (GRCm39)	D93E	possibly damaging	Het
Mtmr14	T	A	6: 113,237,627 (GRCm39)		probably benign	Het
Muc5ac	T	C	7: 141,364,776 (GRCm39)	S1917P	probably benign	Het
Muc6	C	T	7: 141,238,255 (GRCm39)	C75Y	probably damaging	Het
Naip1	A	T	13: 100,563,418 (GRCm39)	H582Q	possibly damaging	Het
Nbeal2	G	A	9: 110,471,211 (GRCm39)	R264*	probably null	Het
Neb	T	C	2: 52,139,388 (GRCm39)	K140E	probably damaging	Het
Nfya	A	G	17: 48,706,026 (GRCm39)	V48A	possibly damaging	Het
Ngf	G	T	3: 102,417,119 (GRCm39)		probably benign	Het
Nsmce2	T	G	15: 59,250,806 (GRCm39)	S26A	probably damaging	Het
Or52s19	T	C	7: 103,007,613 (GRCm39)	T263A	possibly damaging	Het
Or5m13b	T	A	2: 85,754,362 (GRCm39)	I250N	possibly damaging	Het
Or7e177	T	G	9: 20,212,387 (GRCm39)	M297R	probably damaging	Het
Pax1	A	G	2: 147,215,654 (GRCm39)	S424G	probably benign	Het
Pcdhb19	A	T	18: 37,630,235 (GRCm39)	Q10L	probably benign	Het
Pdcl	T	C	2: 37,242,142 (GRCm39)	I203V	probably benign	Het
Pknox1	T	A	17: 31,823,764 (GRCm39)	N379K	probably benign	Het
Plxna1	C	T	6: 89,297,692 (GRCm39)	A1831T	possibly damaging	Het
Prodh	T	G	16: 17,895,677 (GRCm39)	Q360P	probably damaging	Het
Pygo2	T	C	3: 89,340,610 (GRCm39)	V299A	probably damaging	Het
Raf1	C	T	6: 115,609,934 (GRCm39)	G202S	probably benign	Het
Rgs11	T	A	17: 26,426,433 (GRCm39)		probably null	Het
Rmc1	C	T	18: 12,322,328 (GRCm39)	R594C	probably damaging	Het
Rnf13	A	G	3: 57,709,889 (GRCm39)	D144G	probably damaging	Het
Rtel1	T	C	2: 180,962,839 (GRCm39)	C31R	probably damaging	Het
Rubcnl	T	A	14: 75,279,898 (GRCm39)	I427K	probably damaging	Het
Sec23ip	C	T	7: 128,380,775 (GRCm39)		probably benign	Het
Slc25a26	T	A	6: 94,569,507 (GRCm39)		probably null	Het
Slc6a7	A	G	18: 61,135,183 (GRCm39)		probably benign	Het
Slco6b1	A	T	1: 96,915,562 (GRCm39)		noncoding transcript	Het
Spata17	A	G	1: 186,844,798 (GRCm39)	V111A	probably damaging	Het
Spata22	T	A	11: 73,221,979 (GRCm39)	M1K	probably null	Het
Svep1	C	T	4: 58,116,608 (GRCm39)	D881N	possibly damaging	Het
Sypl2	T	A	3: 108,126,411 (GRCm39)	N67I	possibly damaging	Het
Tasor	A	G	14: 27,193,725 (GRCm39)	D975G	probably benign	Het
Tenm3	T	C	8: 48,689,755 (GRCm39)	Y1944C	probably damaging	Het
Tm9sf4	G	T	2: 153,037,233 (GRCm39)	V365L	probably benign	Het
Tmc3	T	C	7: 83,256,950 (GRCm39)	V401A	probably damaging	Het
Trpm2	C	T	10: 77,761,659 (GRCm39)	G997D	probably damaging	Het
Unc5b	A	T	10: 60,608,076 (GRCm39)	S675T	probably damaging	Het
Vmn1r217	A	G	13: 23,298,107 (GRCm39)	M265T	probably benign	Het
Vps54	T	A	11: 21,250,259 (GRCm39)	D548E	probably benign	Het
Wdfy3	A	G	5: 102,065,277 (GRCm39)	V1297A	probably benign	Het
Wdr46	T	A	17: 34,159,997 (GRCm39)	F70I	probably benign	Het
Zdbf2	C	T	1: 63,343,165 (GRCm39)	Q515*	probably null	Het
Zfp710	T	A	7: 79,731,721 (GRCm39)	C299*	probably null	Het

Other mutations in Irs2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00963:Irs2	APN	8	11,055,867 (GRCm39)	missense	probably benign	0.00
IGL01328:Irs2	APN	8	11,054,792 (GRCm39)	missense	probably damaging	0.99
IGL01875:Irs2	APN	8	11,056,221 (GRCm39)	missense	probably damaging	0.98
IGL02444:Irs2	APN	8	11,056,306 (GRCm39)	missense	probably benign	0.03
IGL02448:Irs2	APN	8	11,057,862 (GRCm39)	missense	probably benign	0.21
IGL02945:Irs2	APN	8	11,057,781 (GRCm39)	missense	probably damaging	1.00
IGL03068:Irs2	APN	8	11,054,974 (GRCm39)	missense	probably damaging	0.99
beefed	UTSW	8	11,056,522 (GRCm39)	nonsense	probably null
Dum_dum	UTSW	8	11,037,012 (GRCm39)	makesense	probably null
Lush	UTSW	8	11,056,678 (GRCm39)	nonsense	probably null
muscular	UTSW	8	11,054,659 (GRCm39)	nonsense	probably null
Plink	UTSW	8	11,055,121 (GRCm39)	missense	probably damaging	0.99
R0062:Irs2	UTSW	8	11,055,723 (GRCm39)	missense	possibly damaging	0.65
R0062:Irs2	UTSW	8	11,055,723 (GRCm39)	missense	possibly damaging	0.65
R0107:Irs2	UTSW	8	11,054,691 (GRCm39)	missense	probably damaging	1.00
R0501:Irs2	UTSW	8	11,056,396 (GRCm39)	missense	probably damaging	1.00
R0565:Irs2	UTSW	8	11,054,592 (GRCm39)	missense	probably damaging	0.98
R2042:Irs2	UTSW	8	11,057,580 (GRCm39)	missense	probably damaging	0.99
R2268:Irs2	UTSW	8	11,057,586 (GRCm39)	missense	probably damaging	0.98
R2518:Irs2	UTSW	8	11,055,352 (GRCm39)	missense	probably benign	0.00
R2762:Irs2	UTSW	8	11,056,408 (GRCm39)	missense	probably damaging	1.00
R3623:Irs2	UTSW	8	11,057,643 (GRCm39)	missense	probably damaging	1.00
R3624:Irs2	UTSW	8	11,057,643 (GRCm39)	missense	probably damaging	1.00
R5022:Irs2	UTSW	8	11,037,012 (GRCm39)	makesense	probably null
R5270:Irs2	UTSW	8	11,056,678 (GRCm39)	nonsense	probably null
R5377:Irs2	UTSW	8	11,055,277 (GRCm39)	missense	probably benign	0.00
R5604:Irs2	UTSW	8	11,055,007 (GRCm39)	missense	possibly damaging	0.84
R6049:Irs2	UTSW	8	11,056,805 (GRCm39)	missense	probably benign	0.01
R6219:Irs2	UTSW	8	11,055,121 (GRCm39)	missense	probably damaging	0.99
R6654:Irs2	UTSW	8	11,056,486 (GRCm39)	missense	probably damaging	1.00
R6726:Irs2	UTSW	8	11,054,961 (GRCm39)	missense	possibly damaging	0.86
R6813:Irs2	UTSW	8	11,054,659 (GRCm39)	nonsense	probably null
R6934:Irs2	UTSW	8	11,054,697 (GRCm39)	missense	probably damaging	0.99
R7261:Irs2	UTSW	8	11,057,018 (GRCm39)	missense	possibly damaging	0.95
R7285:Irs2	UTSW	8	11,056,797 (GRCm39)	missense	probably damaging	0.99
R7458:Irs2	UTSW	8	11,057,739 (GRCm39)	missense	probably damaging	0.99
R7757:Irs2	UTSW	8	11,056,522 (GRCm39)	nonsense	probably null
R8347:Irs2	UTSW	8	11,058,000 (GRCm39)	missense	possibly damaging	0.82
R8348:Irs2	UTSW	8	11,054,974 (GRCm39)	missense	probably damaging	0.98
R8377:Irs2	UTSW	8	11,054,848 (GRCm39)	nonsense	probably null
R8444:Irs2	UTSW	8	11,056,683 (GRCm39)	missense	probably damaging	0.99
R8912:Irs2	UTSW	8	11,056,655 (GRCm39)	missense	probably damaging	0.96
R9229:Irs2	UTSW	8	11,057,400 (GRCm39)	missense	probably damaging	1.00
R9344:Irs2	UTSW	8	11,057,289 (GRCm39)	nonsense	probably null
R9405:Irs2	UTSW	8	11,055,061 (GRCm39)	missense	possibly damaging	0.95
R9484:Irs2	UTSW	8	11,057,334 (GRCm39)	missense	probably damaging	0.99
R9736:Irs2	UTSW	8	11,058,217 (GRCm39)	missense	probably damaging	1.00
Z1176:Irs2	UTSW	8	11,056,185 (GRCm39)	missense	probably damaging	0.97

Predicted Primers

PCR Primer
(F):5'- ACTCGTCAAGGGACATGAAACCCG -3'
(R):5'- GCAGCTTATGAACATTCGCCGC -3'

Sequencing Primer
(F):5'- GCCAGAGTCACTTTGCTCG -3'
(R):5'- GACAGCTTCTTCTTCATCGAGG -3'

Posted On

2013-04-16