Mutagenetix > Incidental Mutations

Incidental Mutation 'R1468:Lrp5'

197777

Institutional Source

Beutler Lab

Gene Symbol

Lrp5

Ensembl Gene

ENSMUSG00000024913

Gene Name

low density lipoprotein receptor-related protein 5

Synonyms

LR3, LRP7

MMRRC Submission

039521-MU

Accession Numbers

Is this an essential gene?

Probably essential (E-score: 0.934) question?

Stock #

R1468 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

3584828-3686564 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 3620191 bp

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 638 (T638A)

Ref Sequence

ENSEMBL: ENSMUSP00000025856 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000025856] [ENSMUST00000176867] [ENSMUST00000177294] [ENSMUST00000177330]

Predicted Effect

possibly damaging
Transcript: ENSMUST00000025856
AA Change: T638A

PolyPhen 2 Score 0.763 (Sensitivity: 0.85; Specificity: 0.92)

SMART Domains

Protein: ENSMUSP00000025856
Gene: ENSMUSG00000024913
AA Change: T638A

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: ENSMUST00000176867

SMART Domains

Protein: ENSMUSP00000135654
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
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

Predicted Effect

probably benign
Transcript: ENSMUST00000177294

SMART Domains

Protein: ENSMUSP00000134771
Gene: ENSMUSG00000024913

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

Meta Mutation Damage Score

0.2078

Coding Region Coverage

1x: 97.4%
3x: 96.7%
10x: 94.6%
20x: 90.1%

Validation Efficiency

98% (106/108)

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: 112 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2900092C05Rik	T	G	7: 12,512,580	M1R	probably null	Het
4933440N22Rik	C	A	6: 117,907,579		probably benign	Het
5031439G07Rik	G	T	15: 84,953,144	P280T	probably damaging	Het
Abca2	C	T	2: 25,441,296	S1267L	probably damaging	Het
Acsl3	A	T	1: 78,706,409	R719S	probably benign	Het
Adam1a	A	T	5: 121,519,776		probably null	Het
Adamts7	T	C	9: 90,188,798		probably benign	Het
Adgrf3	G	A	5: 30,202,229		probably benign	Het
Aldh6a1	T	C	12: 84,441,770	E89G	possibly damaging	Het
Ankrd36	A	G	11: 5,575,752	Y238C	probably damaging	Het
Ankrd65	G	A	4: 155,792,905	R291Q	probably benign	Het
Ano2	C	T	6: 125,796,264	R287W	probably damaging	Het
Ap1ar	A	G	3: 127,812,566	I125T	probably benign	Het
Arid1b	A	G	17: 5,242,922	D705G	probably damaging	Het
Asb18	T	A	1: 89,996,283	N86I	probably damaging	Het
Bicral	A	T	17: 46,824,593	S564T	probably benign	Het
Bpifa6	A	G	2: 153,989,272	M253V	probably benign	Het
Braf	T	C	6: 39,665,083	D194G	probably damaging	Het
Brinp3	C	A	1: 146,901,962	P716T	probably benign	Het
C7	T	A	15: 5,012,149	Y425F	probably damaging	Het
Ccdc102a	T	C	8: 94,906,086	K421R	probably benign	Het
Cep89	G	A	7: 35,420,963		probably null	Het
Chgb	A	T	2: 132,792,800	M221L	probably benign	Het
Chst14	A	G	2: 118,927,664	Y313C	probably damaging	Het
Ciita	G	A	16: 10,513,288		probably null	Het
Clec12b	A	T	6: 129,380,640	I85N	probably damaging	Het
Clec2e	G	T	6: 129,093,496	Y187*	probably null	Het
Crbn	T	C	6: 106,790,843	K229E	probably benign	Het
Ctdspl2	A	T	2: 121,981,281	Q201L	probably benign	Het
Ctrb1	G	T	8: 111,689,409		probably benign	Het
Cyp2c55	T	A	19: 39,011,081	V77E	probably damaging	Het
Cyp2c69	A	C	19: 39,849,395	D414E	probably damaging	Het
Ddx47	T	C	6: 135,011,740		probably benign	Het
Dlg1	A	G	16: 31,842,822		probably null	Het
Dnah5	C	A	15: 28,230,463	S169*	probably null	Het
Dock4	C	A	12: 40,755,810	T927K	probably benign	Het
Esrp2	T	G	8: 106,133,821	D259A	probably damaging	Het
Fam169a	A	G	13: 97,118,530	K418R	probably benign	Het
Fam207a	A	G	10: 77,497,526		probably benign	Het
Fancm	A	T	12: 65,099,293	I597F	probably damaging	Het
Fastkd2	G	T	1: 63,732,226		probably benign	Het
Fat1	G	A	8: 45,010,545	V1375M	probably damaging	Het
Fbxw10	A	T	11: 62,862,638	D486V	probably damaging	Het
Fech	C	T	18: 64,470,673		probably benign	Het
Fermt1	C	T	2: 132,925,022	E342K	probably benign	Het
Foxp1	T	A	6: 98,978,220	H195L	possibly damaging	Het
Gfra1	T	A	19: 58,451,975	I138L	probably benign	Het
Gm12185	T	C	11: 48,915,674	D230G	possibly damaging	Het
Gm14403	T	A	2: 177,507,231		probably benign	Het
Gpd2	A	C	2: 57,355,774	T439P	probably damaging	Het
Gpm6a	A	T	8: 55,037,350	K20N	probably damaging	Het
Hc	A	T	2: 34,983,807	Y158*	probably null	Het
Hectd4	A	T	5: 121,349,172	D3410V	possibly damaging	Het
Il17b	G	A	18: 61,690,412		probably null	Het
Irx4	G	T	13: 73,265,576	R55L	possibly damaging	Het
Itgav	A	T	2: 83,765,901		probably benign	Het
Lama3	T	C	18: 12,441,107	V582A	probably benign	Het
Ldhd	G	T	8: 111,627,293	A425E	possibly damaging	Het
Lrp1b	C	T	2: 40,927,829		probably null	Het
Lrrk1	A	C	7: 66,259,974	F1996C	probably damaging	Het
Ly6h	G	A	15: 75,566,137	S21L	probably benign	Het
Mctp1	T	C	13: 76,825,273	V431A	probably benign	Het
Metap2	C	T	10: 93,871,483		probably null	Het
Mfsd2b	T	A	12: 4,870,536	K94*	probably null	Het
Micall2	A	G	5: 139,719,342	L79P	probably damaging	Het
Mucl2	T	C	15: 103,897,407	T95A	possibly damaging	Het
Myo15	A	T	11: 60,506,006	T2634S	probably damaging	Het
Myo5b	G	T	18: 74,740,503	V1467L	probably damaging	Het
Nfic	G	T	10: 81,420,580	D105E	probably damaging	Het
Nrd1	T	A	4: 109,016,668	F227Y	probably benign	Het
Nrp2	A	T	1: 62,738,299	I88F	probably damaging	Het
Nup160	A	T	2: 90,700,543	H515L	probably benign	Het
Nup205	G	A	6: 35,225,982		probably null	Het
Oas1g	G	A	5: 120,882,006	T179I	probably benign	Het
Ogfr	A	T	2: 180,594,750	E376V	probably damaging	Het
Olfr1212	T	G	2: 88,959,043	Y192*	probably null	Het
Olfr1241	A	T	2: 89,482,511	V208D	possibly damaging	Het
Olfr166	T	G	16: 19,487,628	S263R	probably benign	Het
Olfr478	C	T	7: 108,032,388		probably null	Het
Olfr646	G	T	7: 104,106,689	V137F	possibly damaging	Het
Pard3b	T	C	1: 62,345,029	V851A	probably benign	Het
Pcdhb16	A	T	18: 37,478,089	Y34F	probably damaging	Het
Pikfyve	T	C	1: 65,251,666	Y1215H	probably damaging	Het
Pkhd1	A	T	1: 20,523,341	V1516E	probably damaging	Het
Pla2g4a	A	T	1: 149,887,593		probably benign	Het
Ptprg	A	T	14: 12,190,767	I818F	probably benign	Het
Ralgapb	A	G	2: 158,462,253	E644G	possibly damaging	Het
Rbm45	A	G	2: 76,372,115	I127M	probably damaging	Het
Rtp2	T	C	16: 23,927,470	Y157C	probably damaging	Het
Sema3f	A	T	9: 107,687,572		probably benign	Het
Sf3b3	A	T	8: 110,837,374	Y329N	probably damaging	Het
Sfxn1	A	G	13: 54,085,627		probably null	Het
Shkbp1	A	T	7: 27,345,326	C447S	probably damaging	Het
Sipa1l3	A	G	7: 29,322,260	S689P	possibly damaging	Het
Slc7a8	A	G	14: 54,733,199	S332P	probably damaging	Het
Slit1	C	A	19: 41,608,384	C1092F	probably damaging	Het
Stard9	A	G	2: 120,703,197	I619V	possibly damaging	Het
Sycp3	T	C	10: 88,469,592	V185A	possibly damaging	Het
Taar9	A	T	10: 24,109,484	N17K	possibly damaging	Het
Tbkbp1	T	C	11: 97,148,988	E102G	probably damaging	Het
Tex44	A	G	1: 86,427,112	N248D	probably benign	Het
Tmem63b	C	G	17: 45,678,978	R88P	possibly damaging	Het
Tnpo1	C	T	13: 98,850,157	V781I	probably benign	Het
Tonsl	C	T	15: 76,636,561		probably null	Het
Ttc6	A	G	12: 57,674,677	K984R	possibly damaging	Het
Usp34	A	G	11: 23,441,171	E2263G	probably damaging	Het
Usp8	A	G	2: 126,754,927	K875E	probably damaging	Het
Vapb	C	T	2: 173,762,112		probably benign	Het
Vmn1r223	A	G	13: 23,249,868	I211V	possibly damaging	Het
Vmn2r81	G	A	10: 79,293,662	V796I	probably damaging	Het
Wdr90	A	T	17: 25,854,053	V856D	probably damaging	Het
Wnk2	T	A	13: 49,082,095	T615S	probably 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
r18	UTSW	19		small insertion
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
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
R4825:Lrp5	UTSW	19	3614292	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

Predicted Primers

PCR Primer
(F):5'- AGGCGTTTACAACCTCATGCCAG -3'
(R):5'- TAGGTGGCAGGAATCCAGTCACAC -3'

Sequencing Primer
(F):5'- CTGACATCAGTCCAGTAGATGTG -3'
(R):5'- CACACAACTGTGAGCTGGTG -3'

Posted On

2014-05-23