Mutagenetix > Incidental Mutation

Incidental Mutation 'R0565:Irs2'

46126

Institutional Source

Beutler Lab

Gene Symbol

Irs2

Ensembl Gene

ENSMUSG00000038894

Gene Name

insulin receptor substrate 2

Synonyms

Irs-2

MMRRC Submission

038756-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.579) question?

Stock #

R0565 (G1)

Quality Score

171

Status

Validated

Chromosome

Chromosomal Location

11034681-11058458 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 11054592 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Valine to Alanine at position 1280 (V1280A)

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: V1280A

PolyPhen 2 Score 0.976 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000038514
Gene: ENSMUSG00000038894
AA Change: V1280A

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

0.0995

Coding Region Coverage

1x: 99.6%
3x: 98.8%
10x: 96.8%
20x: 93.6%

Validation Efficiency

100% (73/73)

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: 71 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930562C15Rik	A	T	16: 4,682,200 (GRCm39)	H1010L	probably benign	Het
A2ml1	C	A	6: 128,545,706 (GRCm39)	E474*	probably null	Het
Agtr1b	T	C	3: 20,369,838 (GRCm39)	H256R	probably damaging	Het
Amacr	C	T	15: 10,982,032 (GRCm39)	A46V	possibly damaging	Het
Atosb	A	T	4: 43,034,647 (GRCm39)		probably benign	Het
Cabp5	A	T	7: 13,135,260 (GRCm39)	M67L	probably damaging	Het
Caskin2	T	C	11: 115,691,842 (GRCm39)	E981G	probably damaging	Het
Ccdc88a	A	G	11: 29,411,042 (GRCm39)		probably benign	Het
Cd180	A	G	13: 102,839,382 (GRCm39)		probably benign	Het
Cd200l1	T	A	16: 45,264,536 (GRCm39)		probably benign	Het
Cemip	G	A	7: 83,613,318 (GRCm39)	H627Y	probably damaging	Het
Cep131	G	T	11: 119,964,588 (GRCm39)	H289Q	probably damaging	Het
Cep350	G	A	1: 155,836,941 (GRCm39)		probably benign	Het
Cfap52	A	T	11: 67,840,425 (GRCm39)	C169S	probably benign	Het
Cps1	A	T	1: 67,205,608 (GRCm39)	T544S	possibly damaging	Het
Cul7	T	C	17: 46,962,929 (GRCm39)	S187P	probably damaging	Het
Dhx40	C	A	11: 86,661,993 (GRCm39)	R688L	probably damaging	Het
E330034G19Rik	C	A	14: 24,356,985 (GRCm39)	Q174K	probably benign	Het
Efna5	T	C	17: 63,188,031 (GRCm39)	Y32C	probably damaging	Het
Ethe1	A	G	7: 24,307,314 (GRCm39)	H176R	probably benign	Het
Exoc3	A	G	13: 74,330,394 (GRCm39)		probably null	Het
Fam135b	T	A	15: 71,362,686 (GRCm39)	N232Y	possibly damaging	Het
Fndc9	C	T	11: 46,128,984 (GRCm39)	L168F	probably damaging	Het
Fpr-rs3	G	A	17: 20,844,283 (GRCm39)	A286V	probably damaging	Het
Immt	T	A	6: 71,823,467 (GRCm39)		probably benign	Het
Ipo7	T	C	7: 109,648,800 (GRCm39)		probably benign	Het
Ipo8	A	T	6: 148,688,221 (GRCm39)	L747H	probably damaging	Het
Ireb2	A	T	9: 54,807,267 (GRCm39)	N610Y	probably damaging	Het
Kcnj3	T	A	2: 55,485,276 (GRCm39)	M458K	probably benign	Het
Kl	A	G	5: 150,904,409 (GRCm39)	K387R	possibly damaging	Het
L3mbtl2	C	A	15: 81,568,487 (GRCm39)		probably benign	Het
Lamb1	A	C	12: 31,348,914 (GRCm39)	I649L	probably benign	Het
Lipm	A	C	19: 34,093,906 (GRCm39)	L274F	probably benign	Het
Lrfn3	A	G	7: 30,060,216 (GRCm39)	V3A	probably benign	Het
Lrrc8c	A	C	5: 105,754,894 (GRCm39)	D223A	probably damaging	Het
Ltn1	C	A	16: 87,212,898 (GRCm39)	K554N	probably benign	Het
Mertk	T	C	2: 128,613,403 (GRCm39)	I473T	probably benign	Het
Mfsd12	C	A	10: 81,197,243 (GRCm39)	N245K	probably benign	Het
Mmp16	A	G	4: 17,987,705 (GRCm39)	D89G	probably damaging	Het
Myo5a	T	A	9: 75,087,394 (GRCm39)	N1083K	probably benign	Het
Ncapd3	C	T	9: 26,999,294 (GRCm39)	A1290V	probably benign	Het
Nefm	A	G	14: 68,362,070 (GRCm39)	S65P	probably damaging	Het
Nt5c2	C	T	19: 46,886,064 (GRCm39)	R220H	probably damaging	Het
Or4c102	T	A	2: 88,422,353 (GRCm39)	D68E	probably benign	Het
Osbpl1a	A	T	18: 12,892,501 (GRCm39)	S438R	probably damaging	Het
Pcdhb5	T	C	18: 37,453,820 (GRCm39)	S67P	possibly damaging	Het
Per3	A	T	4: 151,118,409 (GRCm39)	I228N	probably damaging	Het
Pnpla7	T	G	2: 24,870,129 (GRCm39)		probably benign	Het
Ppp1r15b	G	T	1: 133,064,391 (GRCm39)		probably benign	Het
Psmd2	G	T	16: 20,479,176 (GRCm39)	L678F	probably null	Het
Ptch2	A	G	4: 116,963,340 (GRCm39)		probably benign	Het
Ranbp2	T	A	10: 58,312,158 (GRCm39)	D959E	probably benign	Het
Rph3al	C	T	11: 75,724,227 (GRCm39)		probably null	Het
Sec31b	T	A	19: 44,512,992 (GRCm39)	E499V	probably damaging	Het
Sel1l	T	C	12: 91,778,663 (GRCm39)	I667M	probably benign	Het
Sel1l	C	A	12: 91,780,719 (GRCm39)	V641L	possibly damaging	Het
Slc7a1	T	A	5: 148,288,879 (GRCm39)	I123F	probably damaging	Het
Smarca2	G	A	19: 26,659,275 (GRCm39)	R855Q	possibly damaging	Het
Sphk1	G	T	11: 116,427,184 (GRCm39)		probably benign	Het
Spink12	C	A	18: 44,237,755 (GRCm39)	S11*	probably null	Het
Sstr2	A	T	11: 113,516,445 (GRCm39)	I342F	probably benign	Het
Stxbp1	T	C	2: 32,709,860 (GRCm39)	T78A	probably benign	Het
Trim11	T	A	11: 58,881,410 (GRCm39)	S434R	probably damaging	Het
Ubr2	T	C	17: 47,266,812 (GRCm39)	E1113G	probably damaging	Het
Upb1	T	A	10: 75,264,188 (GRCm39)		probably benign	Het
Vit	T	A	17: 78,932,266 (GRCm39)	C458S	probably damaging	Het
Vmn1r58	T	C	7: 5,414,165 (GRCm39)	I22V	probably benign	Het
Vps25	T	C	11: 101,149,731 (GRCm39)		probably benign	Het
Wbp2	G	T	11: 115,973,211 (GRCm39)	D65E	possibly damaging	Het
Wdr72	A	G	9: 74,124,588 (GRCm39)	D980G	probably benign	Het
Xkr8	A	C	4: 132,458,228 (GRCm39)		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
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'- GTTGGCAATTAAGCCAAGGAAGCAC -3'
(R):5'- CCTTTGCCCACAATTCCAAGCG -3'

Sequencing Primer
(F):5'- GCACTAGTAAGAGTGGCATCC -3'
(R):5'- CTGTGGAAAATGTCTCACTCAGG -3'

Posted On

2013-06-11