Mutagenetix > Incidental Mutation

Incidental Mutation 'R6511:Lrp5'

519936

Institutional Source

Beutler Lab

Gene Symbol

Lrp5

Ensembl Gene

ENSMUSG00000024913

Gene Name

low density lipoprotein receptor-related protein 5

Synonyms

LRP7, LR3

MMRRC Submission

044639-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.923) question?

Stock #

R6511 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

3634828-3736564 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 3702296 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Tryptophan at position 174 (R174W)

Ref Sequence

ENSEMBL: ENSMUSP00000134983 (fasta)

Gene Model

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

AlphaFold

Q91VN0

Predicted Effect

probably damaging
Transcript: ENSMUST00000025856
AA Change: R174W

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

SMART Domains

Protein: ENSMUSP00000025856
Gene: ENSMUSG00000024913
AA Change: R174W

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 damaging
Transcript: ENSMUST00000176867
AA Change: R174W

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

SMART Domains

Protein: ENSMUSP00000135654
Gene: ENSMUSG00000024913
AA Change: R174W

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 damaging
Transcript: ENSMUST00000177330
AA Change: R174W

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

SMART Domains

Protein: ENSMUSP00000134983
Gene: ENSMUSG00000024913
AA Change: R174W

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

0.5835

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 97.9%
20x: 93.5%

Validation Efficiency

100% (39/39)

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: 38 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcc5	G	A	16: 20,195,344 (GRCm39)	H718Y	probably damaging	Het
Abcc8	G	A	7: 45,800,285 (GRCm39)	T499I	possibly damaging	Het
Azin2	C	A	4: 128,828,259 (GRCm39)	R316L	probably damaging	Het
Cep85l	C	T	10: 53,154,188 (GRCm39)	V702I	probably benign	Het
Cfap69	A	T	5: 5,667,220 (GRCm39)	C442S	probably damaging	Het
Commd3	G	A	2: 18,679,650 (GRCm39)	G148R	probably benign	Het
Cyfip2	T	C	11: 46,087,135 (GRCm39)	T1252A	probably benign	Het
Cyp4a30b	A	T	4: 115,313,905 (GRCm39)	D162V	probably damaging	Het
Exoc3l	G	T	8: 106,019,887 (GRCm39)	T346K	probably benign	Het
Gas8	T	C	8: 124,250,896 (GRCm39)	V123A	probably benign	Het
Hmcn2	T	G	2: 31,246,354 (GRCm39)	D774E	possibly damaging	Het
Itga1	G	T	13: 115,129,037 (GRCm39)	S540R	probably damaging	Het
Itpr2	T	C	6: 146,231,225 (GRCm39)	N1145S	probably damaging	Het
Kcnc2	C	T	10: 112,297,972 (GRCm39)		probably benign	Het
Lrrn4	T	G	2: 132,712,246 (GRCm39)	S526R	probably benign	Het
Map3k6	G	A	4: 132,975,389 (GRCm39)	R708H	probably damaging	Het
Mefv	T	C	16: 3,533,810 (GRCm39)	T154A	probably benign	Het
Mrtfb	T	A	16: 13,197,714 (GRCm39)	S66R	probably damaging	Het
Mtif2	G	T	11: 29,486,949 (GRCm39)	A320S	possibly damaging	Het
Nos2	A	G	11: 78,846,290 (GRCm39)		probably null	Het
Or4k15b	A	G	14: 50,272,266 (GRCm39)	L198P	probably damaging	Het
Or9g4	A	G	2: 85,505,184 (GRCm39)	S104P	possibly damaging	Het
Pip5k1c	T	C	10: 81,146,651 (GRCm39)	Y44H	probably damaging	Het
Ppp1r13b	T	C	12: 111,798,001 (GRCm39)	E972G	probably damaging	Het
Prdm12	T	C	2: 31,530,321 (GRCm39)	S71P	probably damaging	Het
Prkag2	G	T	5: 25,305,286 (GRCm39)		probably benign	Het
Ptprb	T	C	10: 116,182,725 (GRCm39)	L1467P	probably damaging	Het
Rnf43	G	A	11: 87,622,989 (GRCm39)	V697I	probably benign	Het
Rpl7	C	A	1: 16,173,889 (GRCm39)	A12S	probably benign	Het
Slc25a54	T	G	3: 109,001,572 (GRCm39)	I120S	possibly damaging	Het
Slc41a2	T	C	10: 83,119,652 (GRCm39)	H370R	probably damaging	Het
Speer1d	A	G	5: 11,307,275 (GRCm39)	Y51C	probably benign	Het
Sv2c	C	T	13: 96,185,033 (GRCm39)	V215I	probably benign	Het
Synpo2l	T	C	14: 20,712,518 (GRCm39)	E34G	probably damaging	Het
Tubgcp5	T	A	7: 55,467,140 (GRCm39)	C703*	probably null	Het
Vmn1r158	T	C	7: 22,490,116 (GRCm39)	K31R	probably benign	Het
Vmn2r106	C	T	17: 20,488,725 (GRCm39)	C558Y	probably damaging	Het
Zfp2	A	T	11: 50,791,234 (GRCm39)	C270S	probably damaging	Het

Other mutations in Lrp5

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00834:Lrp5	APN	19	3,699,404 (GRCm39)	missense	probably benign
IGL00902:Lrp5	APN	19	3,650,774 (GRCm39)	missense	probably damaging	1.00
IGL02032:Lrp5	APN	19	3,665,886 (GRCm39)	splice site	probably benign
IGL02331:Lrp5	APN	19	3,641,816 (GRCm39)	missense	possibly damaging	0.64
IGL02401:Lrp5	APN	19	3,643,585 (GRCm39)	missense	probably damaging	1.00
IGL02471:Lrp5	APN	19	3,652,408 (GRCm39)	missense	probably benign	0.31
IGL02572:Lrp5	APN	19	3,664,283 (GRCm39)	missense	probably benign	0.17
IGL02637:Lrp5	APN	19	3,680,269 (GRCm39)	missense	probably benign	0.03
IGL02696:Lrp5	APN	19	3,652,253 (GRCm39)	missense	probably benign
IGL02742:Lrp5	APN	19	3,654,022 (GRCm39)	missense	probably damaging	0.99
IGL02804:Lrp5	APN	19	3,650,777 (GRCm39)	missense	possibly damaging	0.63
IGL03089:Lrp5	APN	19	3,670,314 (GRCm39)	splice site	probably null
IGL03243:Lrp5	APN	19	3,680,159 (GRCm39)	missense	probably benign	0.12
Contrarian	UTSW	19	3,709,355 (GRCm39)	missense	probably damaging	1.00
Contrarian2	UTSW	19	3,702,296 (GRCm39)	missense	probably damaging	1.00
lucent	UTSW	19	3,736,353 (GRCm39)	critical splice donor site	probably null
Microtome	UTSW	19	3,672,638 (GRCm39)	missense	probably damaging	1.00
r18	UTSW	19	0 ()	small insertion
Spicule	UTSW	19	3,662,197 (GRCm39)	critical splice donor site	probably null
Stirrup	UTSW	19	3,650,753 (GRCm39)	missense	probably damaging	1.00
PIT4494001:Lrp5	UTSW	19	3,660,091 (GRCm39)	missense	probably damaging	1.00
R0219:Lrp5	UTSW	19	3,647,349 (GRCm39)	missense	probably damaging	1.00
R0526:Lrp5	UTSW	19	3,678,295 (GRCm39)	missense	probably damaging	1.00
R0597:Lrp5	UTSW	19	3,650,777 (GRCm39)	missense	possibly damaging	0.63
R0883:Lrp5	UTSW	19	3,655,308 (GRCm39)	missense	probably damaging	1.00
R1086:Lrp5	UTSW	19	3,699,476 (GRCm39)	missense	probably benign	0.28
R1417:Lrp5	UTSW	19	3,636,425 (GRCm39)	missense	probably benign	0.04
R1468:Lrp5	UTSW	19	3,670,191 (GRCm39)	missense	possibly damaging	0.76
R1468:Lrp5	UTSW	19	3,670,191 (GRCm39)	missense	possibly damaging	0.76
R1533:Lrp5	UTSW	19	3,664,234 (GRCm39)	missense	probably benign	0.17
R1538:Lrp5	UTSW	19	3,697,585 (GRCm39)	missense	possibly damaging	0.70
R1856:Lrp5	UTSW	19	3,647,346 (GRCm39)	missense	probably benign	0.18
R1930:Lrp5	UTSW	19	3,660,131 (GRCm39)	missense	probably benign	0.02
R1931:Lrp5	UTSW	19	3,660,131 (GRCm39)	missense	probably benign	0.02
R1932:Lrp5	UTSW	19	3,660,131 (GRCm39)	missense	probably benign	0.02
R1951:Lrp5	UTSW	19	3,670,298 (GRCm39)	missense	possibly damaging	0.89
R2016:Lrp5	UTSW	19	3,660,056 (GRCm39)	missense	probably benign	0.04
R2131:Lrp5	UTSW	19	3,672,708 (GRCm39)	missense	possibly damaging	0.87
R2153:Lrp5	UTSW	19	3,664,339 (GRCm39)	missense	probably benign	0.22
R2403:Lrp5	UTSW	19	3,647,430 (GRCm39)	missense	probably damaging	1.00
R3158:Lrp5	UTSW	19	3,665,849 (GRCm39)	missense	probably damaging	0.97
R3771:Lrp5	UTSW	19	3,662,330 (GRCm39)	missense	probably damaging	1.00
R3772:Lrp5	UTSW	19	3,662,330 (GRCm39)	missense	probably damaging	1.00
R3773:Lrp5	UTSW	19	3,662,330 (GRCm39)	missense	probably damaging	1.00
R3825:Lrp5	UTSW	19	3,655,290 (GRCm39)	nonsense	probably null
R3887:Lrp5	UTSW	19	3,662,330 (GRCm39)	missense	probably damaging	1.00
R3888:Lrp5	UTSW	19	3,662,330 (GRCm39)	missense	probably damaging	1.00
R3893:Lrp5	UTSW	19	3,662,330 (GRCm39)	missense	probably damaging	1.00
R3917:Lrp5	UTSW	19	3,662,330 (GRCm39)	missense	probably damaging	1.00
R4279:Lrp5	UTSW	19	3,641,778 (GRCm39)	missense	possibly damaging	0.94
R4714:Lrp5	UTSW	19	3,709,454 (GRCm39)	missense	probably damaging	1.00
R4825:Lrp5	UTSW	19	3,664,292 (GRCm39)	missense	probably damaging	1.00
R5102:Lrp5	UTSW	19	3,709,304 (GRCm39)	missense	probably damaging	0.96
R5138:Lrp5	UTSW	19	3,678,319 (GRCm39)	missense	probably benign	0.03
R5497:Lrp5	UTSW	19	3,652,319 (GRCm39)	missense	probably damaging	1.00
R5632:Lrp5	UTSW	19	3,672,512 (GRCm39)	missense	probably benign
R5887:Lrp5	UTSW	19	3,654,094 (GRCm39)	missense	probably benign	0.01
R5950:Lrp5	UTSW	19	3,652,333 (GRCm39)	missense	probably benign	0.17
R5987:Lrp5	UTSW	19	3,678,299 (GRCm39)	missense	probably damaging	1.00
R6080:Lrp5	UTSW	19	3,678,316 (GRCm39)	missense	probably benign	0.32
R6181:Lrp5	UTSW	19	3,678,427 (GRCm39)	missense	probably damaging	1.00
R6236:Lrp5	UTSW	19	3,680,483 (GRCm39)	splice site	probably null
R6332:Lrp5	UTSW	19	3,709,355 (GRCm39)	missense	probably damaging	1.00
R6641:Lrp5	UTSW	19	3,702,287 (GRCm39)	missense	probably damaging	1.00
R6791:Lrp5	UTSW	19	3,650,753 (GRCm39)	missense	probably damaging	1.00
R6865:Lrp5	UTSW	19	3,670,013 (GRCm39)	critical splice donor site	probably null
R6906:Lrp5	UTSW	19	3,672,638 (GRCm39)	missense	probably damaging	1.00
R6922:Lrp5	UTSW	19	3,655,301 (GRCm39)	missense	probably damaging	1.00
R7091:Lrp5	UTSW	19	3,680,184 (GRCm39)	missense	probably damaging	1.00
R7303:Lrp5	UTSW	19	3,641,774 (GRCm39)	missense	probably damaging	0.99
R7368:Lrp5	UTSW	19	3,670,085 (GRCm39)	missense	possibly damaging	0.95
R7381:Lrp5	UTSW	19	3,643,588 (GRCm39)	missense	probably benign	0.20
R7385:Lrp5	UTSW	19	3,662,197 (GRCm39)	critical splice donor site	probably null
R7392:Lrp5	UTSW	19	3,660,199 (GRCm39)	missense	probably damaging	1.00
R7448:Lrp5	UTSW	19	3,699,439 (GRCm39)	missense	probably benign	0.01
R7585:Lrp5	UTSW	19	3,654,094 (GRCm39)	missense	possibly damaging	0.88
R7662:Lrp5	UTSW	19	3,736,353 (GRCm39)	critical splice donor site	probably null
R7984:Lrp5	UTSW	19	3,662,342 (GRCm39)	missense	probably damaging	1.00
R8056:Lrp5	UTSW	19	3,647,337 (GRCm39)	missense	probably damaging	0.98
R8391:Lrp5	UTSW	19	3,654,185 (GRCm39)	missense	probably damaging	1.00
R8881:Lrp5	UTSW	19	3,641,015 (GRCm39)	missense	probably damaging	0.98
R8885:Lrp5	UTSW	19	3,702,170 (GRCm39)	missense	probably damaging	1.00
R9051:Lrp5	UTSW	19	3,680,156 (GRCm39)	missense	possibly damaging	0.89
R9263:Lrp5	UTSW	19	3,654,190 (GRCm39)	missense	probably damaging	1.00
R9376:Lrp5	UTSW	19	3,670,286 (GRCm39)	missense	probably benign	0.00
R9400:Lrp5	UTSW	19	3,635,272 (GRCm39)	missense	probably benign	0.00
R9536:Lrp5	UTSW	19	3,672,672 (GRCm39)	missense	probably damaging	1.00
R9600:Lrp5	UTSW	19	3,641,712 (GRCm39)	missense	probably benign	0.00
Z1177:Lrp5	UTSW	19	3,678,345 (GRCm39)	nonsense	probably null

Predicted Primers

PCR Primer
(F):5'- CCTGAGTTAAGGAGCCTCAAC -3'
(R):5'- AAAGTTTGGGTCCCTCAAACG -3'

Sequencing Primer
(F):5'- CTCCCTGAGGACAGCAGATATAGTG -3'
(R):5'- GATAGTCACTCGTTATTTCTCACAGG -3'

Posted On

2018-06-06