Mutagenetix > Incidental Mutation

Incidental Mutation 'R4451:Irs1'

328948

Institutional Source

Beutler Lab

Gene Symbol

Irs1

Ensembl Gene

ENSMUSG00000055980

Gene Name

insulin receptor substrate 1

Synonyms

G972R, IRS-1

MMRRC Submission

041712-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.620) question?

Stock #

R4451 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

82210822-82269137 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 82266749 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Cysteine at position 489 (Y489C)

Ref Sequence

ENSEMBL: ENSMUSP00000063795 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000069799]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000069799
AA Change: Y489C

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000063795
Gene: ENSMUSG00000055980
AA Change: Y489C

Domain	Start	End	E-Value	Type
PH	13	117	8.13e-14	SMART
low complexity region	123	143	N/A	INTRINSIC
IRS	155	257	1.19e-35	SMART
PTBI	155	257	7.8e-60	SMART
low complexity region	263	276	N/A	INTRINSIC
low complexity region	378	399	N/A	INTRINSIC
low complexity region	407	419	N/A	INTRINSIC
low complexity region	551	568	N/A	INTRINSIC
low complexity region	662	689	N/A	INTRINSIC
low complexity region	784	794	N/A	INTRINSIC
low complexity region	801	810	N/A	INTRINSIC
low complexity region	824	837	N/A	INTRINSIC
low complexity region	1019	1040	N/A	INTRINSIC
low complexity region	1051	1062	N/A	INTRINSIC
low complexity region	1111	1127	N/A	INTRINSIC
low complexity region	1185	1200	N/A	INTRINSIC

Meta Mutation Damage Score

0.0898

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 97.0%
20x: 94.6%

Validation Efficiency

100% (43/43)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a protein which is phosphorylated by insulin receptor tyrosine kinase. Mutations in this gene are associated with type II diabetes and susceptibility to insulin resistance. [provided by RefSeq, Nov 2009]
PHENOTYPE: Homozygotes for targeted null mutations exhibit 50 percent reductions in body weights at birth and at 4 months of age, impaired glucose tolerance, and mild insulin and IGF-1 resistance. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 38 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Arap2	A	C	5: 62,906,513 (GRCm39)	F169V	probably benign	Het
Baiap2l1	T	A	5: 144,215,362 (GRCm39)	Y381F	probably damaging	Het
Cdc27	A	T	11: 104,408,221 (GRCm39)	M563K	probably benign	Het
Cela3b	G	A	4: 137,148,355 (GRCm39)		probably benign	Het
Cyp2c29	A	T	19: 39,279,270 (GRCm39)	D50V	probably damaging	Het
Dbpht2	A	T	12: 74,345,806 (GRCm39)		noncoding transcript	Het
Dnah9	T	A	11: 65,772,467 (GRCm39)	Q3755L	probably benign	Het
Dnajc2	T	C	5: 21,962,792 (GRCm39)	T588A	possibly damaging	Het
Dync2h1	T	A	9: 6,983,477 (GRCm39)	R4022S	probably benign	Het
Gm20481	T	G	17: 35,191,109 (GRCm39)		probably benign	Het
Gm7347	A	G	5: 26,260,004 (GRCm39)	I182T	possibly damaging	Het
Gns	G	A	10: 121,212,601 (GRCm39)	G188S	probably damaging	Het
Grm5	T	G	7: 87,724,340 (GRCm39)		probably null	Het
Gstm4	T	C	3: 107,951,291 (GRCm39)		probably null	Het
Il7r	T	A	15: 9,513,034 (GRCm39)	K158N	probably benign	Het
Kcns1	C	T	2: 164,010,598 (GRCm39)	E54K	possibly damaging	Het
Klra5	T	A	6: 129,885,797 (GRCm39)	R31*	probably null	Het
Krt13	T	C	11: 100,008,827 (GRCm39)	T409A	unknown	Het
Lce1e	C	T	3: 92,614,967 (GRCm39)	G127S	unknown	Het
Mfsd14a	T	C	3: 116,456,127 (GRCm39)	M1V	probably null	Het
Micall2	T	C	5: 139,692,852 (GRCm39)	E891G	probably damaging	Het
Mpeg1	A	T	19: 12,440,596 (GRCm39)	K685*	probably null	Het
Nbea	A	G	3: 55,899,753 (GRCm39)		probably null	Het
Nup155	A	G	15: 8,180,366 (GRCm39)	M1148V	probably benign	Het
Or51aa5	A	G	7: 103,167,184 (GRCm39)	S136P	probably damaging	Het
Or5m3b	T	C	2: 85,872,303 (GRCm39)	S215P	probably damaging	Het
Otof	T	A	5: 30,542,508 (GRCm39)	D695V	possibly damaging	Het
Ptf1a	G	T	2: 19,451,092 (GRCm39)	A141S	possibly damaging	Het
Pxmp2	A	T	5: 110,425,531 (GRCm39)	V168E	probably damaging	Het
Rab11fip1	T	C	8: 27,644,505 (GRCm39)	K427E	probably damaging	Het
Susd2	A	G	10: 75,475,232 (GRCm39)	V526A	probably damaging	Het
Tbx2	T	C	11: 85,731,643 (GRCm39)	S647P	probably damaging	Het
Tg	A	G	15: 66,637,996 (GRCm39)	T651A	probably benign	Het
Trim68	T	A	7: 102,333,680 (GRCm39)	M1L	probably damaging	Het
Ttn	A	C	2: 76,584,250 (GRCm39)	L20540*	probably null	Het
Usf3	A	T	16: 44,038,251 (GRCm39)	K910N	possibly damaging	Het
Vmn1r14	T	G	6: 57,211,213 (GRCm39)	Y220D	possibly damaging	Het
Vmn1r209	T	A	13: 22,990,668 (GRCm39)	K7N	probably benign	Het

Other mutations in Irs1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00325:Irs1	APN	1	82,266,204 (GRCm39)	missense	probably benign	0.01
IGL00534:Irs1	APN	1	82,266,192 (GRCm39)	missense	probably benign
IGL01926:Irs1	APN	1	82,267,680 (GRCm39)	missense	probably damaging	0.98
IGL02130:Irs1	APN	1	82,267,188 (GRCm39)	missense	probably damaging	1.00
IGL03338:Irs1	APN	1	82,266,122 (GRCm39)	missense	probably benign	0.05
Hoverboard	UTSW	1	82,267,819 (GRCm39)	nonsense	probably null
runt	UTSW	1	82,265,453 (GRCm39)	frame shift	probably null
runt2	UTSW	1	82,264,688 (GRCm39)	nonsense	probably null
Sprite	UTSW	1	82,265,830 (GRCm39)	nonsense	probably null
R0019:Irs1	UTSW	1	82,264,977 (GRCm39)	nonsense	probably null
R0063:Irs1	UTSW	1	82,266,580 (GRCm39)	missense	probably damaging	1.00
R0063:Irs1	UTSW	1	82,266,580 (GRCm39)	missense	probably damaging	1.00
R0318:Irs1	UTSW	1	82,266,381 (GRCm39)	missense	probably benign	0.01
R1199:Irs1	UTSW	1	82,267,347 (GRCm39)	missense	probably damaging	1.00
R1363:Irs1	UTSW	1	82,265,009 (GRCm39)	missense	probably benign	0.02
R1584:Irs1	UTSW	1	82,267,165 (GRCm39)	missense	probably benign	0.24
R1874:Irs1	UTSW	1	82,267,574 (GRCm39)	frame shift	probably null
R1903:Irs1	UTSW	1	82,267,182 (GRCm39)	missense	probably damaging	1.00
R1929:Irs1	UTSW	1	82,266,180 (GRCm39)	missense	probably benign
R1986:Irs1	UTSW	1	82,266,486 (GRCm39)	missense	probably damaging	1.00
R2136:Irs1	UTSW	1	82,267,763 (GRCm39)	missense	probably damaging	1.00
R2179:Irs1	UTSW	1	82,267,940 (GRCm39)	missense	possibly damaging	0.81
R2271:Irs1	UTSW	1	82,266,180 (GRCm39)	missense	probably benign
R2760:Irs1	UTSW	1	82,266,291 (GRCm39)	missense	probably damaging	1.00
R3721:Irs1	UTSW	1	82,267,806 (GRCm39)	missense	probably benign	0.11
R3821:Irs1	UTSW	1	82,267,770 (GRCm39)	missense	probably benign
R4306:Irs1	UTSW	1	82,265,685 (GRCm39)	missense	probably benign	0.11
R4420:Irs1	UTSW	1	82,266,171 (GRCm39)	missense	possibly damaging	0.94
R4479:Irs1	UTSW	1	82,265,015 (GRCm39)	missense	probably damaging	1.00
R4771:Irs1	UTSW	1	82,265,696 (GRCm39)	missense	probably benign	0.00
R4782:Irs1	UTSW	1	82,265,184 (GRCm39)	missense	probably benign	0.00
R4836:Irs1	UTSW	1	82,265,453 (GRCm39)	frame shift	probably null
R4880:Irs1	UTSW	1	82,265,453 (GRCm39)	frame shift	probably null
R4881:Irs1	UTSW	1	82,265,453 (GRCm39)	frame shift	probably null
R5031:Irs1	UTSW	1	82,264,688 (GRCm39)	nonsense	probably null
R5053:Irs1	UTSW	1	82,264,643 (GRCm39)	missense	probably benign
R5418:Irs1	UTSW	1	82,266,491 (GRCm39)	missense	probably damaging	1.00
R5595:Irs1	UTSW	1	82,267,646 (GRCm39)	missense	probably damaging	1.00
R5698:Irs1	UTSW	1	82,266,455 (GRCm39)	missense	probably benign	0.01
R6381:Irs1	UTSW	1	82,265,405 (GRCm39)	missense	possibly damaging	0.66
R6563:Irs1	UTSW	1	82,266,128 (GRCm39)	missense	probably damaging	0.98
R7002:Irs1	UTSW	1	82,265,981 (GRCm39)	missense	probably benign	0.13
R7095:Irs1	UTSW	1	82,267,819 (GRCm39)	nonsense	probably null
R7195:Irs1	UTSW	1	82,265,177 (GRCm39)	missense	probably benign	0.13
R7216:Irs1	UTSW	1	82,267,476 (GRCm39)	missense	probably damaging	0.98
R7361:Irs1	UTSW	1	82,266,835 (GRCm39)	nonsense	probably null
R7490:Irs1	UTSW	1	82,264,985 (GRCm39)	missense	probably damaging	0.99
R7540:Irs1	UTSW	1	82,265,723 (GRCm39)	missense	not run
R7706:Irs1	UTSW	1	82,265,412 (GRCm39)	missense	probably damaging	1.00
R7910:Irs1	UTSW	1	82,267,802 (GRCm39)	missense	probably benign	0.06
R7912:Irs1	UTSW	1	82,267,605 (GRCm39)	missense	probably benign
R7962:Irs1	UTSW	1	82,266,443 (GRCm39)	missense	possibly damaging	0.57
R8139:Irs1	UTSW	1	82,267,460 (GRCm39)	missense	probably damaging	1.00
R8158:Irs1	UTSW	1	82,267,254 (GRCm39)	missense	probably damaging	1.00
R8159:Irs1	UTSW	1	82,266,290 (GRCm39)	missense	probably damaging	1.00
R8187:Irs1	UTSW	1	82,266,021 (GRCm39)	missense	probably damaging	1.00
R8288:Irs1	UTSW	1	82,265,682 (GRCm39)	nonsense	probably null
R8436:Irs1	UTSW	1	82,267,970 (GRCm39)	missense	possibly damaging	0.96
R8865:Irs1	UTSW	1	82,265,830 (GRCm39)	nonsense	probably null
R8950:Irs1	UTSW	1	82,264,652 (GRCm39)	missense	probably benign
R9591:Irs1	UTSW	1	82,265,969 (GRCm39)	missense	probably benign	0.00
X0063:Irs1	UTSW	1	82,266,629 (GRCm39)	missense	probably damaging	1.00
X0065:Irs1	UTSW	1	82,267,086 (GRCm39)	missense	probably damaging	1.00
Z1177:Irs1	UTSW	1	82,268,115 (GRCm39)	missense	probably benign	0.29
Z1177:Irs1	UTSW	1	82,266,717 (GRCm39)	missense	possibly damaging	0.87

Predicted Primers

PCR Primer
(F):5'- TTCCTCAATAGAAGCCACTGAAG -3'
(R):5'- CATGGCTCCACTTCAGACTG -3'

Sequencing Primer
(F):5'- CTCAATAGAAGCCACTGAAGACTGTG -3'
(R):5'- AGACTGTCTCTTCCCGAGG -3'

Posted On

2015-07-21