Mutagenetix > Incidental Mutation

Incidental Mutation 'R7757:Irs2'

597617

Institutional Source

Beutler Lab

Gene Symbol

Irs2

Ensembl Gene

ENSMUSG00000038894

Gene Name

insulin receptor substrate 2

Synonyms

Irs-2

MMRRC Submission

045813-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.528) question?

Stock #

R7757 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

11034681-11058458 bp(-) (GRCm39)

Type of Mutation

nonsense

DNA Base Change (assembly)

T to A at 11056522 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Stop codon at position 637 (K637*)

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 null
Transcript: ENSMUST00000040514
AA Change: K637*

SMART Domains

Protein: ENSMUSP00000038514
Gene: ENSMUSG00000038894
AA Change: K637*

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

Meta Mutation Damage Score

0.9755

Coding Region Coverage

1x: 100.0%
3x: 100.0%
10x: 99.7%
20x: 98.9%

Validation Efficiency

96% (70/73)

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: 76 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2700049A03Rik	G	A	12: 71,236,187 (GRCm39)	M1179I	probably benign	Het
6430550D23Rik	T	C	2: 155,845,351 (GRCm39)	T18A	possibly damaging	Het
Acox2	T	C	14: 8,230,166 (GRCm38)	N659S	probably damaging	Het
Agk	T	C	6: 40,353,212 (GRCm39)	V192A	possibly damaging	Het
Ap3b1	T	A	13: 94,664,666 (GRCm39)		probably null	Het
Bche	T	A	3: 73,608,454 (GRCm39)	D324V	probably damaging	Het
Bsn	A	G	9: 107,991,939 (GRCm39)	I1271T	possibly damaging	Het
Capn12	T	C	7: 28,582,246 (GRCm39)	L120P	probably damaging	Het
Cep290	T	A	10: 100,399,296 (GRCm39)	S2273T	probably benign	Het
Ckap4	T	C	10: 84,364,331 (GRCm39)	E244G	probably damaging	Het
Clcn7	T	C	17: 25,375,796 (GRCm39)	Y545H	probably damaging	Het
Cmya5	T	A	13: 93,234,780 (GRCm39)	T103S	possibly damaging	Het
Cplane1	A	T	15: 8,281,711 (GRCm39)	E2850V	unknown	Het
Cpne9	G	A	6: 113,261,406 (GRCm39)	V121M	possibly damaging	Het
Csmd2	T	A	4: 128,377,249 (GRCm39)	I2043N		Het
Disc1	A	G	8: 125,814,243 (GRCm39)	T36A	probably benign	Het
Disp2	T	C	2: 118,621,391 (GRCm39)	Y708H	probably damaging	Het
Dnah3	A	G	7: 119,670,793 (GRCm39)	V635A	probably benign	Het
Dnah3	A	T	7: 119,570,438 (GRCm39)		probably null	Het
Dync1li1	A	G	9: 114,538,345 (GRCm39)	H234R	possibly damaging	Het
Egfr	T	C	11: 16,839,966 (GRCm39)	V660A	possibly damaging	Het
Epb42	T	C	2: 120,858,200 (GRCm39)	R253G	possibly damaging	Het
Fat2	T	A	11: 55,202,247 (GRCm39)	T276S	probably benign	Het
Fcho2	A	G	13: 98,901,011 (GRCm39)		probably null	Het
Ginm1	A	T	10: 7,655,119 (GRCm39)	I41N	probably damaging	Het
Gm4744	A	G	6: 40,927,367 (GRCm39)		probably benign	Het
Gm49368	C	T	7: 127,711,398 (GRCm39)	R701C	probably damaging	Het
Gpr37	T	A	6: 25,688,207 (GRCm39)	I297F	probably benign	Het
Gprc5a	T	A	6: 135,056,342 (GRCm39)	I263N	possibly damaging	Het
Gys2	A	T	6: 142,400,177 (GRCm39)	S345T	probably benign	Het
Hk2	T	C	6: 82,719,896 (GRCm39)	M255V	possibly damaging	Het
Ibtk	A	C	9: 85,579,290 (GRCm39)	S1202A	possibly damaging	Het
Il23r	T	G	6: 67,400,965 (GRCm39)	D455A	probably benign	Het
Jak2	T	C	19: 29,260,946 (GRCm39)	V314A	probably benign	Het
Mei1	C	T	15: 81,966,824 (GRCm39)		probably benign	Het
Mill1	T	C	7: 17,996,391 (GRCm39)	M69T	probably benign	Het
Mms22l	T	C	4: 24,598,884 (GRCm39)		probably null	Het
Mup8	C	A	4: 60,220,332 (GRCm39)	Q133H	probably benign	Het
Mup8	T	A	4: 60,220,333 (GRCm39)	Q133L	probably benign	Het
Mycbp2	A	T	14: 103,429,055 (GRCm39)	Y2374N	probably damaging	Het
Nbeal1	A	T	1: 60,296,609 (GRCm39)	K1166N	probably damaging	Het
Nlrc4	T	A	17: 74,755,191 (GRCm39)	R8S	probably benign	Het
Nrcam	C	T	12: 44,596,681 (GRCm39)	Q25*	probably null	Het
Nudt16	A	C	9: 105,008,760 (GRCm39)	M47R	probably damaging	Het
Nup62	T	C	7: 44,478,419 (GRCm39)	S145P	probably benign	Het
Or10d1	A	G	9: 39,483,761 (GRCm39)	W265R	probably benign	Het
Or4c117	T	C	2: 88,955,333 (GRCm39)	I247M	possibly damaging	Het
Osbpl1a	A	T	18: 13,066,657 (GRCm39)	V34D	probably benign	Het
Otogl	T	A	10: 107,712,782 (GRCm39)	N521Y	probably damaging	Het
Pcdhb14	T	A	18: 37,582,887 (GRCm39)	D664E	possibly damaging	Het
Pex5l	T	C	3: 33,136,300 (GRCm39)		probably benign	Het
Pkhd1	A	G	1: 20,632,639 (GRCm39)	L592P	probably damaging	Het
Plxdc2	A	G	2: 16,734,187 (GRCm39)	H480R	probably benign	Het
Rnf216	T	A	5: 143,065,991 (GRCm39)	K532N	probably damaging	Het
Schip1	C	A	3: 68,525,028 (GRCm39)	Q358K	probably damaging	Het
Sdc2	A	T	15: 33,028,233 (GRCm39)	E117V	possibly damaging	Het
Septin11	A	T	5: 93,319,323 (GRCm39)		probably null	Het
Shprh	A	T	10: 11,037,924 (GRCm39)	E420V	probably benign	Het
Ska1	T	A	18: 74,330,044 (GRCm39)	H232L	probably benign	Het
Slc36a4	A	G	9: 15,630,956 (GRCm39)	N25S	possibly damaging	Het
Slitrk3	G	A	3: 72,958,172 (GRCm39)	T200M	probably damaging	Het
Smad2	C	T	18: 76,421,084 (GRCm39)	H138Y	probably benign	Het
Snx21	T	C	2: 164,628,085 (GRCm39)	S34P	probably damaging	Het
Sos2	A	G	12: 69,695,359 (GRCm39)	V126A	probably damaging	Het
Srcap	C	T	7: 127,129,966 (GRCm39)	T596I	probably damaging	Het
Stk31	T	G	6: 49,383,877 (GRCm39)		probably null	Het
Stox1	T	C	10: 62,499,743 (GRCm39)	D939G	probably damaging	Het
Syne2	G	T	12: 76,108,553 (GRCm39)	C979F	possibly damaging	Het
Tanc2	C	A	11: 105,667,684 (GRCm39)	N88K	possibly damaging	Het
Tll2	A	T	19: 41,084,447 (GRCm39)	V677E	probably damaging	Het
Ttn	T	C	2: 76,748,834 (GRCm39)	T4072A	probably benign	Het
Unc13b	CAGAGC	CAGAGCGAGAGC	4: 43,177,341 (GRCm39)		probably benign	Het
Unc13b	CGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGC	CGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGCCAGAGC	4: 43,177,312 (GRCm39)		probably benign	Het
Unc13b	AGAGCC	AGAGCCCGAGCC	4: 43,177,330 (GRCm39)		probably benign	Het
Vmn2r43	A	T	7: 8,258,253 (GRCm39)	F320Y	possibly damaging	Het
Zscan4f	G	T	7: 11,135,205 (GRCm39)	G204*	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
R0147:Irs2	UTSW	8	11,057,568 (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
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'- TTTACTGGGAAGGTCCTGCC -3'
(R):5'- GGACTTATTCCCTAACCACGC -3'

Sequencing Primer
(F):5'- TCCTGCCCACCCCTGAAG -3'
(R):5'- TAACCACGCCTGCCAGG -3'

Posted On

2019-11-26