Mutagenetix > Incidental Mutation

Incidental Mutation 'R9229:Irs2'

700099

Institutional Source

Beutler Lab

Gene Symbol

Irs2

Ensembl Gene

ENSMUSG00000038894

Gene Name

insulin receptor substrate 2

Synonyms

Irs-2

MMRRC Submission

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.528) question?

Stock #

R9229 (G1)

Quality Score

175.009

Status

Validated

Chromosome

Chromosomal Location

11034681-11058458 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to C at 11057400 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Leucine to Arginine at position 344 (L344R)

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: L344R

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

SMART Domains

Protein: ENSMUSP00000038514
Gene: ENSMUSG00000038894
AA Change: L344R

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 98.9%

Validation Efficiency

97% (77/79)

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: 83 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Actr10	A	G	12: 70,990,259 (GRCm39)	T104A	probably damaging	Het
Agbl1	G	A	7: 76,774,270 (GRCm39)	V1065I	unknown	Het
Agpat1	G	T	17: 34,830,663 (GRCm39)	V196L	probably null	Het
Agxt2	T	A	15: 10,409,597 (GRCm39)	V499E	probably damaging	Het
Amy2a1	T	A	3: 113,325,955 (GRCm39)		probably benign	Het
Ankrd35	A	G	3: 96,592,215 (GRCm39)	T834A	probably benign	Het
Arhgef18	T	A	8: 3,479,314 (GRCm39)	S51T	probably benign	Het
Armc12	A	C	17: 28,751,345 (GRCm39)	D113A	probably benign	Het
Azin1	T	A	15: 38,490,646 (GRCm39)	I436F	probably benign	Het
B3galnt2	T	C	13: 14,166,107 (GRCm39)	V334A	probably damaging	Het
Ccdc68	C	T	18: 70,080,203 (GRCm39)	H183Y	probably benign	Het
Cd180	TA	TAA	13: 102,841,514 (GRCm39)		probably null	Het
Cemip	A	T	7: 83,606,833 (GRCm39)	W795R	probably damaging	Het
Cenpj	C	T	14: 56,802,176 (GRCm39)	E130K	possibly damaging	Het
Ciao1	G	C	2: 127,089,062 (GRCm39)	C52W	probably damaging	Het
Cmya5	A	G	13: 93,232,176 (GRCm39)	S971P	possibly damaging	Het
Cnot2	A	T	10: 116,384,960 (GRCm39)	L9*	probably null	Het
Coro1c	G	T	5: 114,003,747 (GRCm39)	H91N	probably damaging	Het
Crbn	A	T	6: 106,777,017 (GRCm39)	M1K	probably null	Het
Ctsb	T	A	14: 63,373,112 (GRCm39)	W90R	probably damaging	Het
Ctse	A	G	1: 131,595,862 (GRCm39)	I185V	probably damaging	Het
Dennd1b	G	T	1: 138,981,100 (GRCm39)	E105*	probably null	Het
Eif4a3l1	A	G	6: 136,306,141 (GRCm39)	I201V	possibly damaging	Het
Exoc5	G	A	14: 49,251,710 (GRCm39)	Q679*	probably null	Het
Firrm	A	T	1: 163,794,659 (GRCm39)	W512R	probably damaging	Het
Gabrg3	G	A	7: 56,374,268 (GRCm39)	R433C	probably damaging	Het
Gria2	C	A	3: 80,709,689 (GRCm39)	M1I	probably null	Het
H1f6	T	C	13: 23,880,029 (GRCm39)	S61P	probably damaging	Het
Hoxb6	A	T	11: 96,191,645 (GRCm39)	Q189L	probably damaging	Het
Hoxd10	A	G	2: 74,524,600 (GRCm39)	N304S	possibly damaging	Het
Hps4	G	A	5: 112,525,905 (GRCm39)	S642N	possibly damaging	Het
Htra4	A	T	8: 25,528,557 (GRCm39)	C112S	probably damaging	Het
Ide	T	C	19: 37,261,598 (GRCm39)	T715A		Het
Ipo13	A	T	4: 117,758,801 (GRCm39)	I688N	probably damaging	Het
Kat6a	A	G	8: 23,429,987 (GRCm39)	T1781A	unknown	Het
Lin7a	G	T	10: 107,247,844 (GRCm39)	V172L	probably damaging	Het
Lpcat1	G	T	13: 73,653,650 (GRCm39)	E282D	probably damaging	Het
Mcf2l	A	G	8: 13,063,584 (GRCm39)	T963A	probably benign	Het
Mfsd14a	G	A	3: 116,439,118 (GRCm39)	A128V	probably benign	Het
Mfsd6	C	G	1: 52,747,903 (GRCm39)	G321R	probably damaging	Het
Mill2	C	T	7: 18,590,475 (GRCm39)	T185I	probably damaging	Het
Mpped1	C	T	15: 83,738,673 (GRCm39)	T270I	possibly damaging	Het
Mrtfb	G	T	16: 13,230,185 (GRCm39)	A957S	possibly damaging	Het
Myh9	T	A	15: 77,675,017 (GRCm39)	Y300F	possibly damaging	Het
Nlrp2	T	A	7: 5,304,052 (GRCm39)	T953S	possibly damaging	Het
Nlrp4e	T	A	7: 23,020,799 (GRCm39)	S429T	probably benign	Het
Nphp3	T	A	9: 103,913,376 (GRCm39)	Y1003N	probably damaging	Het
Nrap	T	C	19: 56,310,339 (GRCm39)	K1588R	probably benign	Het
Odad2	C	A	18: 7,127,324 (GRCm39)	R963L	possibly damaging	Het
Or10ag56	G	A	2: 87,139,165 (GRCm39)	V31I	probably benign	Het
Or5b124	T	A	19: 13,611,414 (GRCm39)	V313D	probably damaging	Het
Pam	A	G	1: 97,753,660 (GRCm39)	V870A	probably benign	Het
Peg10	CCACATCAGGATCCACATCAGGATGCACATCAGCATCAGGATCCCCATCAGGATGCACATCAGGATCCACATCAGGATGCACATCAG	CCACATCAGGATCCACATCAGGATGCACATCAG	6: 4,756,398 (GRCm39)		probably benign	Het
Pierce1	C	A	2: 28,352,390 (GRCm39)	M124I	probably damaging	Het
Plin3	A	T	17: 56,591,315 (GRCm39)	V155E	probably damaging	Het
Pmepa1	T	C	2: 173,117,962 (GRCm39)	T6A	probably benign	Het
Pnpla7	G	A	2: 24,873,503 (GRCm39)	V170I	probably damaging	Het
Pramel34	A	T	5: 93,784,089 (GRCm39)	C458*	probably null	Het
Ptprz1	A	G	6: 22,986,283 (GRCm39)	H361R	probably null	Het
Pvalb	T	A	15: 78,086,767 (GRCm39)	I50F	possibly damaging	Het
Relch	A	T	1: 105,614,709 (GRCm39)	I218F	possibly damaging	Het
Rhag	G	A	17: 41,142,081 (GRCm39)	A175T	probably damaging	Het
Slc24a4	T	C	12: 102,200,983 (GRCm39)	V291A	possibly damaging	Het
Slc9b2	G	A	3: 135,042,295 (GRCm39)	E525K	probably benign	Het
Smg7	A	G	1: 152,720,971 (GRCm39)	F747S	possibly damaging	Het
Sorcs1	T	G	19: 50,141,300 (GRCm39)	I1144L	probably benign	Het
Sox1	A	T	8: 12,447,390 (GRCm39)	I344F	possibly damaging	Het
Speer4e2	A	T	5: 15,027,718 (GRCm39)	S53T	probably benign	Het
Spta1	A	T	1: 174,067,750 (GRCm39)	E2059V	probably damaging	Het
Sva	T	A	6: 42,017,050 (GRCm39)	N52K	possibly damaging	Het
Sva	T	A	6: 42,017,052 (GRCm39)	M53K	probably benign	Het
Thsd7b	A	G	1: 129,849,027 (GRCm39)	Y913C	probably damaging	Het
Tiam1	A	G	16: 89,634,719 (GRCm39)	S864P	possibly damaging	Het
Tma16	A	G	8: 66,936,779 (GRCm39)	V16A	probably benign	Het
Tmco1	C	T	1: 167,136,132 (GRCm39)		probably benign	Het
Treml1	A	G	17: 48,673,774 (GRCm39)	S262G	probably benign	Het
Ttn	A	T	2: 76,597,797 (GRCm39)	D19705E	probably benign	Het
Utp20	A	G	10: 88,594,239 (GRCm39)	L2162P	possibly damaging	Het
Vmn2r60	A	G	7: 41,791,723 (GRCm39)	I549V	possibly damaging	Het
Xpo4	T	C	14: 57,851,156 (GRCm39)	N329S	probably benign	Het
Zfp879	T	A	11: 50,723,886 (GRCm39)	H390L	probably damaging	Het
Zranb1	C	T	7: 132,583,117 (GRCm39)	S512F	probably damaging	Het
Zswim8	A	G	14: 20,766,393 (GRCm39)	H847R	probably benign	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
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
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'- TCGTCAAGGGACATGAAACCC -3'
(R):5'- TGAAGGCACTCAAAGAGCTC -3'

Sequencing Primer
(F):5'- AGAGTCACTTTGCTCGGGC -3'
(R):5'- AAAGAGCTCTTCGAGTTCCG -3'

Posted On

2022-02-07