Mutagenetix > Incidental Mutation

Incidental Mutation 'R4825:Lrp5'

371475

Institutional Source

Beutler Lab

Gene Symbol

Lrp5

Ensembl Gene

ENSMUSG00000024913

Gene Name

low density lipoprotein receptor-related protein 5

Synonyms

LR3, LRP7

MMRRC Submission

042441-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.913) question?

Stock #

R4825 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

3584828-3686564 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 3614292 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 812 (Y812H)

Ref Sequence

ENSEMBL: ENSMUSP00000025856 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000025856] [ENSMUST00000177294] [ENSMUST00000177330]

AlphaFold

Q91VN0

Predicted Effect

probably damaging
Transcript: ENSMUST00000025856
AA Change: Y812H

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000025856
Gene: ENSMUSG00000024913
AA Change: Y812H

Domain	Start	End	E-Value	Type
signal peptide	1	30	N/A	INTRINSIC
LY	54	96	1.26e0	SMART
LY	99	141	2.11e-13	SMART
LY	142	185	1.32e-14	SMART
LY	186	228	1.6e-13	SMART
LY	229	270	4e-5	SMART
EGF	297	336	1.01e-1	SMART
LY	364	406	5.15e-8	SMART
LY	407	449	4.12e-16	SMART
LY	450	493	7.68e-16	SMART
LY	494	536	6.24e-16	SMART
LY	537	577	3.73e-5	SMART
EGF	603	640	2.48e-1	SMART
LY	666	708	5.92e-8	SMART
LY	709	751	5.65e-14	SMART
LY	752	795	3.81e-11	SMART
LY	796	837	3.54e-6	SMART
LY	838	877	1.33e-1	SMART
EGF	904	941	1.22e0	SMART
LY	968	1009	4.39e-2	SMART
LY	1015	1057	1.81e0	SMART
LY	1058	1102	9.47e-7	SMART
LY	1103	1145	6.91e-9	SMART
LY	1146	1186	1.53e0	SMART
EGF	1215	1253	2.85e-1	SMART
LDLa	1257	1296	1.23e-13	SMART
LDLa	1297	1333	3.26e-9	SMART
LDLa	1334	1371	1.31e-13	SMART
transmembrane domain	1384	1406	N/A	INTRINSIC
low complexity region	1494	1503	N/A	INTRINSIC
low complexity region	1571	1578	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000177294
AA Change: Y87H

PolyPhen 2 Score 0.434 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000134771
Gene: ENSMUSG00000024913
AA Change: Y87H

Domain	Start	End	E-Value	Type
LY	1	26	1.88e1	SMART
LY	27	70	3.81e-11	SMART
LY	71	112	3.54e-6	SMART
LY	113	152	1.33e-1	SMART
EGF	179	216	1.22e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000177330

SMART Domains

Protein: ENSMUSP00000134983
Gene: ENSMUSG00000024913

Domain	Start	End	E-Value	Type
signal peptide	1	30	N/A	INTRINSIC
LY	54	96	1.26e0	SMART
LY	99	141	2.11e-13	SMART
LY	142	185	1.32e-14	SMART
LY	186	228	1.6e-13	SMART

Coding Region Coverage

1x: 99.1%
3x: 98.4%
10x: 96.8%
20x: 93.8%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis. This protein also acts as a co-receptor with Frizzled protein family members for transducing signals by Wnt proteins and was originally cloned on the basis of its association with type 1 diabetes mellitus in humans. This protein plays a key role in skeletal homeostasis and many bone density related diseases are caused by mutations in this gene. Mutations in this gene also cause familial exudative vitreoretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
PHENOTYPE: Homozygous mutants show variable bone loss, decreased osteoblast proliferation, impaired glucose tolerance, increased plasma cholesterol on high-fat diet and persistent embryonic eye vascularization, depending on allelic combination and strain background. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 130 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
1700012B07Rik	C	A	11: 109,791,672	L229F	probably benign	Het
A930002H24Rik	A	C	17: 63,863,608	S62A	unknown	Het
Abca12	T	A	1: 71,302,685	Q1039L	possibly damaging	Het
Adgrg5	T	A	8: 94,941,734	F476I	possibly damaging	Het
AI314180	G	A	4: 58,850,911	L421F	probably damaging	Het
Alms1	A	G	6: 85,678,245	K2789E	probably damaging	Het
Arrdc2	G	A	8: 70,839,277		probably null	Het
Atp2b1	T	A	10: 99,009,564	I743K	probably damaging	Het
Atp6v1c2	C	T	12: 17,289,060	G230D	probably benign	Het
AU040320	G	A	4: 126,791,793	C54Y	probably damaging	Het
BC024139	C	T	15: 76,120,317	V680I	possibly damaging	Het
Bckdhb	A	G	9: 83,988,905	D156G	probably damaging	Het
Canx	T	A	11: 50,308,809	D143V	probably benign	Het
Ccdc180	T	A	4: 45,912,794	V591E	possibly damaging	Het
Ccno	T	C	13: 112,988,099	S68P	probably benign	Het
Cdc45	C	T	16: 18,784,863	E527K	probably damaging	Het
Cep290	T	A	10: 100,488,348	D14E	probably damaging	Het
Cgnl1	A	G	9: 71,630,524	V1238A	probably benign	Het
Ciz1	C	T	2: 32,371,741	A455V	probably damaging	Het
Coro2b	T	A	9: 62,454,623	Y86F	probably benign	Het
Csf2ra	C	T	19: 61,226,552	R158Q	probably benign	Het
Cubn	A	T	2: 13,325,225	I2615N	probably damaging	Het
Dhx8	C	T	11: 101,738,170	R129*	probably null	Het
Disc1	T	A	8: 125,135,302	M471K	possibly damaging	Het
Dmxl2	G	T	9: 54,404,041	L1799I	probably benign	Het
Dnah2	A	G	11: 69,423,205	S4108P	probably damaging	Het
Ehmt2	C	G	17: 34,906,964	P211R	probably benign	Het
Eif4g3	A	G	4: 138,194,081	D1557G	probably benign	Het
Epha5	T	C	5: 84,233,840	D384G	probably damaging	Het
Etl4	A	G	2: 20,806,927	I1274V	probably damaging	Het
Fam160a1	G	A	3: 85,673,432	P489S	possibly damaging	Het
Fip1l1	G	A	5: 74,588,205		probably null	Het
Fubp1	T	C	3: 152,217,890		probably null	Het
Glul	T	C	1: 153,903,044	V33A	probably benign	Het
Gm4846	A	G	1: 166,491,668	F167S	probably damaging	Het
Heatr6	T	A	11: 83,758,322	L168M	probably damaging	Het
Hif1a	T	A	12: 73,932,401	I233N	probably damaging	Het
Hivep2	T	A	10: 14,131,319	H1220Q	possibly damaging	Het
Igkv8-21	T	C	6: 70,315,426	I9M	probably benign	Het
Izumo1	T	A	7: 45,624,987	C62*	probably null	Het
Jakmip3	G	A	7: 139,026,766	E424K	probably damaging	Het
Klhl2	A	G	8: 64,752,813	V358A	probably damaging	Het
Klk10	C	G	7: 43,783,598	D139E	probably damaging	Het
Klk14	T	C	7: 43,692,076	C51R	probably damaging	Het
Klk5	T	G	7: 43,845,390	I99S	probably damaging	Het
L3hypdh	T	C	12: 72,077,393	T258A	probably benign	Het
Lrrc40	T	A	3: 158,061,330	L474*	probably null	Het
Mkks	A	T	2: 136,880,655	M194K	probably benign	Het
Mmp20	A	G	9: 7,654,120	D347G	probably damaging	Het
Mmp27	A	G	9: 7,581,194	E460G	probably damaging	Het
Mms22l	T	C	4: 24,536,226	F605S	probably damaging	Het
Mpzl3	A	G	9: 45,068,329	S193G	probably benign	Het
Muc4	A	T	16: 32,751,747	T542S	probably benign	Het
Muc5b	T	C	7: 141,868,465	L4446P	possibly damaging	Het
Mxi1	C	A	19: 53,370,338	S131*	probably null	Het
Nanog	G	T	6: 122,713,340	A210S	probably benign	Het
Nrcam	C	T	12: 44,575,986	Q988*	probably null	Het
Nsg1	C	A	5: 38,159,047		probably benign	Het
Ogfod3	G	A	11: 121,195,201	A189V	probably benign	Het
Olfr1121	T	A	2: 87,372,088	C185*	probably null	Het
Olfr1228	T	C	2: 89,248,690		probably null	Het
Olfr1240	A	G	2: 89,439,865	V138A	probably benign	Het
Olfr1260	G	A	2: 89,978,153	C125Y	probably damaging	Het
Olfr1465	A	T	19: 13,314,320		probably null	Het
Olfr548-ps1	T	A	7: 102,542,380	V148E	possibly damaging	Het
Olfr58	T	G	9: 19,783,576	S148A	possibly damaging	Het
Olfr632	T	C	7: 103,937,503	V41A	probably benign	Het
Olfr920	A	T	9: 38,756,407	T240S	probably damaging	Het
Olfr980	A	T	9: 40,006,742	M69K	possibly damaging	Het
Orc3	A	T	4: 34,571,774	M665K	possibly damaging	Het
Pabpc1	A	G	15: 36,597,011	S591P	probably damaging	Het
Parp6	T	A	9: 59,624,362		probably null	Het
Pcdh1	T	C	18: 38,189,859	M974V	possibly damaging	Het
Pcdhb22	T	A	18: 37,520,660	V727E	possibly damaging	Het
Pex5l	T	C	3: 32,992,985	E272G	probably damaging	Het
Pglyrp2	G	T	17: 32,418,261	N264K	probably benign	Het
Phxr4	T	A	9: 13,431,586		probably benign	Het
Piezo2	A	G	18: 63,144,954	F293S	probably damaging	Het
Pkhd1	T	C	1: 20,537,401	D1077G	probably damaging	Het
Plekhs1	A	G	19: 56,473,268		probably null	Het
Prex1	G	T	2: 166,585,857	C788*	probably null	Het
Prrt3	A	T	6: 113,498,138	M41K	probably benign	Het
Ptgir	T	C	7: 16,908,843	V326A	probably damaging	Het
Ptprg	T	A	14: 12,220,654	D455E	probably damaging	Het
Ptpru	T	A	4: 131,799,603	Q686L	probably benign	Het
Pxdc1	G	T	13: 34,630,360	T190K	probably benign	Het
Rap1b	A	T	10: 117,818,582	C118S	probably benign	Het
Rapgef2	T	C	3: 79,083,227	M915V	probably benign	Het
Rnd2	C	T	11: 101,468,999	L57F	probably damaging	Het
Rpe65	C	T	3: 159,624,681	A495V	probably benign	Het
Samd15	A	G	12: 87,200,834	T98A	possibly damaging	Het
Sdk1	T	G	5: 141,582,294	D82E	probably benign	Het
Slc26a7	T	C	4: 14,546,309	D340G	probably benign	Het
Slc6a15	T	A	10: 103,418,060	M619K	probably benign	Het
Slc7a4	C	A	16: 17,574,521	D350Y	probably damaging	Het
Slk	T	G	19: 47,619,956	N449K	probably benign	Het
Spta1	A	T	1: 174,244,042		probably null	Het
Sptbn5	A	T	2: 120,055,893		probably benign	Het
Srd5a2	A	T	17: 74,047,805	V8D	probably benign	Het
Srgap3	G	A	6: 112,727,310	A906V	probably benign	Het
Stab2	A	T	10: 86,947,147	M679K	probably benign	Het
Stk3	T	C	15: 34,999,908	I291V	probably benign	Het
Supt6	T	A	11: 78,208,134	Q1637L	possibly damaging	Het
Svil	T	C	18: 5,114,564	F2047S	probably damaging	Het
Swsap1	A	G	9: 21,955,988	E76G	probably benign	Het
Syndig1	G	T	2: 149,899,553	G20C	probably damaging	Het
Synj2bp	A	T	12: 81,502,152	N104K	probably damaging	Het
Synpo2	T	A	3: 123,114,419	D416V	probably damaging	Het
Tacc3	G	T	5: 33,672,013	C620F	probably damaging	Het
Tanc1	A	G	2: 59,699,422	E19G	probably damaging	Het
Tarsl2	C	T	7: 65,647,554	A139V	probably benign	Het
Tbc1d22a	T	A	15: 86,351,734	C365S	probably damaging	Het
Tdpoz2	T	C	3: 93,652,074	H197R	possibly damaging	Het
Tha1	A	T	11: 117,869,379	N300K	probably damaging	Het
Tm6sf1	T	A	7: 81,865,260	F70L	probably damaging	Het
Tmem132b	T	A	5: 125,783,433	S581T	probably benign	Het
Tmem206	A	T	1: 191,340,843	I154F	probably damaging	Het
Tnfsf13	G	T	11: 69,685,249	S4*	probably null	Het
Tonsl	G	A	15: 76,633,248	S757L	probably benign	Het
Trem2	G	T	17: 48,351,691	R161S	possibly damaging	Het
Trpm2	A	T	10: 77,941,173	V430E	probably damaging	Het
Ttc14	T	A	3: 33,801,369	D154E	possibly damaging	Het
Ugt2b37	T	C	5: 87,250,639	M313V	possibly damaging	Het
Uhrf1bp1	G	A	17: 27,877,394	A107T	probably damaging	Het
Vmn2r24	A	G	6: 123,815,780	I689V	probably benign	Het
Wdr76	A	G	2: 121,542,494	T601A	probably benign	Het
Xirp1	T	C	9: 120,017,003	D938G	possibly damaging	Het
Zfp608	A	T	18: 54,897,969	D966E	probably benign	Het
Zfp957	A	G	14: 79,214,356	M1T	probably null	Het
Zkscan16	A	T	4: 58,957,809	H697L	possibly damaging	Het

Other mutations in Lrp5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00834:Lrp5	APN	19	3649404	missense	probably benign
IGL00902:Lrp5	APN	19	3600774	missense	probably damaging	1.00
IGL02032:Lrp5	APN	19	3615886	splice site	probably benign
IGL02331:Lrp5	APN	19	3591816	missense	possibly damaging	0.64
IGL02401:Lrp5	APN	19	3593585	missense	probably damaging	1.00
IGL02471:Lrp5	APN	19	3602408	missense	probably benign	0.31
IGL02572:Lrp5	APN	19	3614283	missense	probably benign	0.17
IGL02637:Lrp5	APN	19	3630269	missense	probably benign	0.03
IGL02696:Lrp5	APN	19	3602253	missense	probably benign
IGL02742:Lrp5	APN	19	3604022	missense	probably damaging	0.99
IGL02804:Lrp5	APN	19	3600777	missense	possibly damaging	0.63
IGL03089:Lrp5	APN	19	3620314	splice site	probably null
IGL03243:Lrp5	APN	19	3630159	missense	probably benign	0.12
Contrarian	UTSW	19	3659355	missense	probably damaging	1.00
Contrarian2	UTSW	19	3652296	missense	probably damaging	1.00
lucent	UTSW	19	3686353	critical splice donor site	probably null
Microtome	UTSW	19	3622638	missense	probably damaging	1.00
r18	UTSW	19		small insertion
Spicule	UTSW	19	3612197	critical splice donor site	probably null
Stirrup	UTSW	19	3600753	missense	probably damaging	1.00
PIT4494001:Lrp5	UTSW	19	3610091	missense	probably damaging	1.00
R0219:Lrp5	UTSW	19	3597349	missense	probably damaging	1.00
R0526:Lrp5	UTSW	19	3628295	missense	probably damaging	1.00
R0597:Lrp5	UTSW	19	3600777	missense	possibly damaging	0.63
R0883:Lrp5	UTSW	19	3605308	missense	probably damaging	1.00
R1086:Lrp5	UTSW	19	3649476	missense	probably benign	0.28
R1417:Lrp5	UTSW	19	3586425	missense	probably benign	0.04
R1468:Lrp5	UTSW	19	3620191	missense	possibly damaging	0.76
R1468:Lrp5	UTSW	19	3620191	missense	possibly damaging	0.76
R1533:Lrp5	UTSW	19	3614234	missense	probably benign	0.17
R1538:Lrp5	UTSW	19	3647585	missense	possibly damaging	0.70
R1856:Lrp5	UTSW	19	3597346	missense	probably benign	0.18
R1930:Lrp5	UTSW	19	3610131	missense	probably benign	0.02
R1931:Lrp5	UTSW	19	3610131	missense	probably benign	0.02
R1932:Lrp5	UTSW	19	3610131	missense	probably benign	0.02
R1951:Lrp5	UTSW	19	3620298	missense	possibly damaging	0.89
R2016:Lrp5	UTSW	19	3610056	missense	probably benign	0.04
R2131:Lrp5	UTSW	19	3622708	missense	possibly damaging	0.87
R2153:Lrp5	UTSW	19	3614339	missense	probably benign	0.22
R2403:Lrp5	UTSW	19	3597430	missense	probably damaging	1.00
R3158:Lrp5	UTSW	19	3615849	missense	probably damaging	0.97
R3771:Lrp5	UTSW	19	3612330	missense	probably damaging	1.00
R3772:Lrp5	UTSW	19	3612330	missense	probably damaging	1.00
R3773:Lrp5	UTSW	19	3612330	missense	probably damaging	1.00
R3825:Lrp5	UTSW	19	3605290	nonsense	probably null
R3887:Lrp5	UTSW	19	3612330	missense	probably damaging	1.00
R3888:Lrp5	UTSW	19	3612330	missense	probably damaging	1.00
R3893:Lrp5	UTSW	19	3612330	missense	probably damaging	1.00
R3917:Lrp5	UTSW	19	3612330	missense	probably damaging	1.00
R4279:Lrp5	UTSW	19	3591778	missense	possibly damaging	0.94
R4714:Lrp5	UTSW	19	3659454	missense	probably damaging	1.00
R5102:Lrp5	UTSW	19	3659304	missense	probably damaging	0.96
R5138:Lrp5	UTSW	19	3628319	missense	probably benign	0.03
R5497:Lrp5	UTSW	19	3602319	missense	probably damaging	1.00
R5632:Lrp5	UTSW	19	3622512	missense	probably benign
R5887:Lrp5	UTSW	19	3604094	missense	probably benign	0.01
R5950:Lrp5	UTSW	19	3602333	missense	probably benign	0.17
R5987:Lrp5	UTSW	19	3628299	missense	probably damaging	1.00
R6080:Lrp5	UTSW	19	3628316	missense	probably benign	0.32
R6181:Lrp5	UTSW	19	3628427	missense	probably damaging	1.00
R6236:Lrp5	UTSW	19	3630483	splice site	probably null
R6332:Lrp5	UTSW	19	3659355	missense	probably damaging	1.00
R6511:Lrp5	UTSW	19	3652296	missense	probably damaging	1.00
R6641:Lrp5	UTSW	19	3652287	missense	probably damaging	1.00
R6791:Lrp5	UTSW	19	3600753	missense	probably damaging	1.00
R6865:Lrp5	UTSW	19	3620013	critical splice donor site	probably null
R6906:Lrp5	UTSW	19	3622638	missense	probably damaging	1.00
R6922:Lrp5	UTSW	19	3605301	missense	probably damaging	1.00
R7091:Lrp5	UTSW	19	3630184	missense	probably damaging	1.00
R7303:Lrp5	UTSW	19	3591774	missense	probably damaging	0.99
R7368:Lrp5	UTSW	19	3620085	missense	possibly damaging	0.95
R7381:Lrp5	UTSW	19	3593588	missense	probably benign	0.20
R7385:Lrp5	UTSW	19	3612197	critical splice donor site	probably null
R7392:Lrp5	UTSW	19	3610199	missense	probably damaging	1.00
R7448:Lrp5	UTSW	19	3649439	missense	probably benign	0.01
R7585:Lrp5	UTSW	19	3604094	missense	possibly damaging	0.88
R7662:Lrp5	UTSW	19	3686353	critical splice donor site	probably null
R7984:Lrp5	UTSW	19	3612342	missense	probably damaging	1.00
R8056:Lrp5	UTSW	19	3597337	missense	probably damaging	0.98
R8391:Lrp5	UTSW	19	3604185	missense	probably damaging	1.00
R8881:Lrp5	UTSW	19	3591015	missense	probably damaging	0.98
R8885:Lrp5	UTSW	19	3652170	missense	probably damaging	1.00
R9051:Lrp5	UTSW	19	3630156	missense	possibly damaging	0.89
R9263:Lrp5	UTSW	19	3604190	missense	probably damaging	1.00
R9376:Lrp5	UTSW	19	3620286	missense	probably benign	0.00
R9400:Lrp5	UTSW	19	3585272	missense	probably benign	0.00
R9536:Lrp5	UTSW	19	3622672	missense	probably damaging	1.00
R9600:Lrp5	UTSW	19	3591712	missense	probably benign	0.00
Z1177:Lrp5	UTSW	19	3628345	nonsense	probably null

Predicted Primers

PCR Primer
(F):5'- CCAAGTGACTCATTGGACAGAG -3'
(R):5'- GGGAAACATCACTGACCAGC -3'

Sequencing Primer
(F):5'- CTCATTGGACAGAGCAGGCTG -3'
(R):5'- CTCTGTTTAGCAAGGATTCAACTAAG -3'

Posted On

2016-03-01