Mutagenetix > Incidental Mutations

Incidental Mutation 'R0063:Irs1'

43758

Institutional Source

Beutler Lab

Gene Symbol

Irs1

Ensembl Gene

ENSMUSG00000055980

Gene Name

insulin receptor substrate 1

Synonyms

G972R, IRS-1

MMRRC Submission

038355-MU

Accession Numbers

Is this an essential gene?

Possibly essential (E-score: 0.584) question?

Stock #

R0063 (G1)

Quality Score

220

Status

Validated

Chromosome

Chromosomal Location

82233101-82291416 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 82288859 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Aspartic acid at position 545 (E545D)

Ref Sequence

ENSEMBL: ENSMUSP00000063795 (fasta)

Gene Model

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

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000069799
AA Change: E545D

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000063795
Gene: ENSMUSG00000055980
AA Change: E545D

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

0.6467

Coding Region Coverage

1x: 99.2%
3x: 98.4%
10x: 96.6%
20x: 93.8%

Validation Efficiency

97% (69/71)

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: 68 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930562C15Rik	C	T	16: 4,861,048	R245*	probably null	Het
4930563I02Rik	T	A	14: 60,096,028		probably benign	Het
9330182L06Rik	T	C	5: 9,440,709		probably benign	Het
Acss1	T	C	2: 150,627,292	T435A	probably damaging	Het
Aoc2	T	A	11: 101,326,071	S327T	probably damaging	Het
Arid5a	T	A	1: 36,318,564	Y252N	probably damaging	Het
AU040320	T	C	4: 126,839,672	Y662H	probably damaging	Het
B4gat1	T	A	19: 5,039,707	L244*	probably null	Het
Bcam	C	T	7: 19,766,848	V134I	probably benign	Het
Btbd16	A	T	7: 130,823,166	T426S	probably benign	Het
Btn1a1	C	T	13: 23,465,097		probably null	Het
Cap2	T	C	13: 46,638,032		probably benign	Het
Capn8	T	A	1: 182,602,112	D299E	probably damaging	Het
Cdipt	G	A	7: 126,979,600	V160I	probably benign	Het
Cep164	A	G	9: 45,768,618	S1267P	possibly damaging	Het
Cic	T	A	7: 25,287,140	S1299T	probably damaging	Het
Cic	C	A	7: 25,287,141	S1299Y	probably damaging	Het
Col3a1	T	C	1: 45,330,541		probably benign	Het
Cyb5r3	T	C	15: 83,161,936	T60A	probably benign	Het
Dgkb	T	G	12: 38,604,113	S744A	probably benign	Het
Dock2	T	A	11: 34,756,284		probably null	Het
Ece1	C	T	4: 137,948,581	T422M	probably benign	Het
Ece2	A	G	16: 20,642,317	T442A	probably benign	Het
Eml3	C	A	19: 8,938,478	A644D	probably damaging	Het
Fbp2	A	T	13: 62,854,048	F118I	probably damaging	Het
Foxp1	A	G	6: 98,944,723		probably benign	Het
Gm10801	G	T	2: 98,663,840	S109I	probably benign	Het
Il17rd	G	A	14: 27,082,733	C88Y	probably damaging	Het
Il17rd	C	A	14: 27,082,734	C88*	probably null	Het
Ino80c	A	G	18: 24,106,624	F160S	probably damaging	Het
Ints8	T	C	4: 11,252,857	N75S	probably damaging	Het
Irf2bp1	C	T	7: 19,005,847	R471C	possibly damaging	Het
Lama3	T	C	18: 12,528,705		probably benign	Het
Mast4	C	A	13: 103,334,215		probably benign	Het
Mcc	C	G	18: 44,519,516		probably benign	Het
Nat8f2	A	T	6: 85,867,833	S182R	possibly damaging	Het
Nrcam	G	T	12: 44,550,028	V343F	possibly damaging	Het
Opn5	T	C	17: 42,596,626	S120G	probably damaging	Het
Pdk2	T	C	11: 95,032,480	H106R	probably benign	Het
Pkhd1	G	A	1: 20,211,950	T2889I	probably benign	Het
Pkhd1l1	T	A	15: 44,529,237	L1656H	probably damaging	Het
Plxna2	A	T	1: 194,644,939	T394S	probably benign	Het
Pnpla8	T	A	12: 44,282,832	C56S	probably damaging	Het
Prdm8	G	T	5: 98,184,594	R118L	probably damaging	Het
Prkce	T	C	17: 86,482,111		probably benign	Het
Ptprk	T	A	10: 28,263,767	Y163N	probably damaging	Het
Rbbp8	T	A	18: 11,734,557		probably benign	Het
Rnh1	A	T	7: 141,164,196		probably null	Het
Rtn4	T	A	11: 29,705,527		probably benign	Het
Sephs1	A	G	2: 4,899,560	T250A	probably benign	Het
Slc2a2	T	C	3: 28,717,440	M173T	probably damaging	Het
Slc2a8	T	A	2: 32,979,999		probably null	Het
Tdpoz1	A	T	3: 93,670,814	M221K	probably benign	Het
Tgm7	G	T	2: 121,094,096	H533Q	probably benign	Het
Timm29	C	A	9: 21,593,008	A17E	probably benign	Het
Tmem131	C	T	1: 36,819,128	V713I	probably benign	Het
Tmem89	A	G	9: 108,914,812	N60S	probably benign	Het
Tpx2	A	G	2: 152,880,123	T212A	probably damaging	Het
Trio	G	T	15: 27,881,437		probably benign	Het
Tulp2	T	C	7: 45,520,860		probably benign	Het
Uggt2	A	G	14: 119,007,130		probably benign	Het
Vmn2r5	T	A	3: 64,503,800	E449V	probably benign	Het
Vwa8	A	G	14: 79,164,216		probably benign	Het
Xirp2	A	G	2: 67,509,083	D556G	probably damaging	Het
Xrn1	T	C	9: 95,969,535	L202P	probably damaging	Het
Zfp354a	A	T	11: 51,069,571	H203L	probably damaging	Het
Zfp53	A	C	17: 21,508,105	R133S	probably benign	Het
Zfp787	C	T	7: 6,132,323		probably null	Het

Other mutations in Irs1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00325:Irs1	APN	1	82288483	missense	probably benign	0.01
IGL00534:Irs1	APN	1	82288471	missense	probably benign
IGL01926:Irs1	APN	1	82289959	missense	probably damaging	0.98
IGL02130:Irs1	APN	1	82289467	missense	probably damaging	1.00
IGL03338:Irs1	APN	1	82288401	missense	probably benign	0.05
Hoverboard	UTSW	1	82290098	nonsense	probably null
runt	UTSW	1	82287732	frame shift	probably null
runt2	UTSW	1	82286967	nonsense	probably null
Sprite	UTSW	1	82288109	nonsense	probably null
R0019:Irs1	UTSW	1	82287256	nonsense	probably null
R0063:Irs1	UTSW	1	82288859	missense	probably damaging	1.00
R0318:Irs1	UTSW	1	82288660	missense	probably benign	0.01
R1199:Irs1	UTSW	1	82289626	missense	probably damaging	1.00
R1363:Irs1	UTSW	1	82287288	missense	probably benign	0.02
R1584:Irs1	UTSW	1	82289444	missense	probably benign	0.24
R1874:Irs1	UTSW	1	82289853	frame shift	probably null
R1903:Irs1	UTSW	1	82289461	missense	probably damaging	1.00
R1929:Irs1	UTSW	1	82288459	missense	probably benign
R1986:Irs1	UTSW	1	82288765	missense	probably damaging	1.00
R2136:Irs1	UTSW	1	82290042	missense	probably damaging	1.00
R2179:Irs1	UTSW	1	82290219	missense	possibly damaging	0.81
R2271:Irs1	UTSW	1	82288459	missense	probably benign
R2760:Irs1	UTSW	1	82288570	missense	probably damaging	1.00
R3721:Irs1	UTSW	1	82290085	missense	probably benign	0.11
R3821:Irs1	UTSW	1	82290049	missense	probably benign
R4306:Irs1	UTSW	1	82287964	missense	probably benign	0.11
R4420:Irs1	UTSW	1	82288450	missense	possibly damaging	0.94
R4451:Irs1	UTSW	1	82289028	missense	probably benign	0.00
R4479:Irs1	UTSW	1	82287294	missense	probably damaging	1.00
R4771:Irs1	UTSW	1	82287975	missense	probably benign	0.00
R4782:Irs1	UTSW	1	82287463	missense	probably benign	0.00
R4836:Irs1	UTSW	1	82287732	frame shift	probably null
R4880:Irs1	UTSW	1	82287732	frame shift	probably null
R4881:Irs1	UTSW	1	82287732	frame shift	probably null
R5031:Irs1	UTSW	1	82286967	nonsense	probably null
R5053:Irs1	UTSW	1	82286922	missense	probably benign
R5418:Irs1	UTSW	1	82288770	missense	probably damaging	1.00
R5595:Irs1	UTSW	1	82289925	missense	probably damaging	1.00
R5698:Irs1	UTSW	1	82288734	missense	probably benign	0.01
R6381:Irs1	UTSW	1	82287684	missense	possibly damaging	0.66
R6563:Irs1	UTSW	1	82288407	missense	probably damaging	0.98
R7002:Irs1	UTSW	1	82288260	missense	probably benign	0.13
R7095:Irs1	UTSW	1	82290098	nonsense	probably null
R7195:Irs1	UTSW	1	82287456	missense	probably benign	0.13
R7216:Irs1	UTSW	1	82289755	missense	probably damaging	0.98
R7361:Irs1	UTSW	1	82289114	nonsense	probably null
R7490:Irs1	UTSW	1	82287264	missense	probably damaging	0.99
R7540:Irs1	UTSW	1	82288002	missense	not run
R7706:Irs1	UTSW	1	82287691	missense	probably damaging	1.00
R7910:Irs1	UTSW	1	82290081	missense	probably benign	0.06
R7912:Irs1	UTSW	1	82289884	missense	probably benign
R7962:Irs1	UTSW	1	82288722	missense	possibly damaging	0.57
R8139:Irs1	UTSW	1	82289739	missense	probably damaging	1.00
R8158:Irs1	UTSW	1	82289533	missense	probably damaging	1.00
R8159:Irs1	UTSW	1	82288569	missense	probably damaging	1.00
R8187:Irs1	UTSW	1	82288300	missense	probably damaging	1.00
R8288:Irs1	UTSW	1	82287961	nonsense	probably null
R8436:Irs1	UTSW	1	82290249	missense	possibly damaging	0.96
R8865:Irs1	UTSW	1	82288109	nonsense	probably null
R8950:Irs1	UTSW	1	82286931	missense	probably benign
X0063:Irs1	UTSW	1	82288908	missense	probably damaging	1.00
X0065:Irs1	UTSW	1	82289365	missense	probably damaging	1.00
Z1177:Irs1	UTSW	1	82288996	missense	possibly damaging	0.87
Z1177:Irs1	UTSW	1	82290394	missense	probably benign	0.29

Predicted Primers

PCR Primer
(F):5'- ACCCCAGGAGACATGGGCATATAG -3'
(R):5'- AAGTTCCTTCCGCAGTGTCACC -3'

Sequencing Primer
(F):5'- TGGGCATATAGCCATCATCAGTG -3'
(R):5'- GGAGCTGAGCAATTATATCTGC -3'

Posted On

2013-05-29