Mutagenetix > Incidental Mutation

Incidental Mutation 'R6906:Lrp5'

538805

Institutional Source

Beutler Lab

Gene Symbol

Lrp5

Ensembl Gene

ENSMUSG00000024913

Gene Name

low density lipoprotein receptor-related protein 5

Synonyms

LRP7, LR3

MMRRC Submission

044998-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.924) question?

Stock #

R6906 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

3634828-3736564 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 3672638 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Asparagine at position 557 (I557N)

Ref Sequence

ENSEMBL: ENSMUSP00000135654 (fasta)

Gene Model

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

AlphaFold

Q91VN0

Predicted Effect

possibly damaging
Transcript: ENSMUST00000025856
AA Change: I557N

PolyPhen 2 Score 0.938 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000025856
Gene: ENSMUSG00000024913
AA Change: I557N

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: I557N

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000135654
Gene: ENSMUSG00000024913
AA Change: I557N

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: 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

0.6799

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.2%
20x: 97.3%

Validation Efficiency

98% (45/46)

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: 46 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcf2	A	G	5: 24,773,840 (GRCm39)	F350L	possibly damaging	Het
Ahnak2	T	A	12: 112,748,933 (GRCm39)	T305S	probably benign	Het
Anp32a	A	G	9: 62,284,851 (GRCm39)		probably benign	Het
Aplf	A	G	6: 87,607,068 (GRCm39)	S449P	possibly damaging	Het
Arl6ip4	A	G	5: 124,254,614 (GRCm39)	R36G	possibly damaging	Het
Ascc1	G	A	10: 59,840,674 (GRCm39)	D12N	probably benign	Het
Bin1	C	A	18: 32,554,978 (GRCm39)	H243Q	probably benign	Het
Ccdc168	C	T	1: 44,095,173 (GRCm39)	S1975N	probably benign	Het
Ccdc7a	C	A	8: 129,662,162 (GRCm39)	V547L	unknown	Het
Cntnap5c	T	A	17: 58,702,302 (GRCm39)	N1207K	probably benign	Het
Coro7	C	A	16: 4,451,168 (GRCm39)	R507L	probably benign	Het
Crtap	T	A	9: 114,210,700 (GRCm39)	K291N	probably benign	Het
Csmd3	T	C	15: 47,710,569 (GRCm39)	T1569A	probably benign	Het
Dmrta1	A	G	4: 89,580,203 (GRCm39)	T388A	probably benign	Het
Ehd3	T	C	17: 74,137,333 (GRCm39)	F501L	probably damaging	Het
Fbn2	A	C	18: 58,204,891 (GRCm39)	L1184R	possibly damaging	Het
Fhip1b	G	A	7: 105,037,476 (GRCm39)	T369I	probably damaging	Het
Hsf1	T	C	15: 76,361,919 (GRCm39)		probably null	Het
Hycc1	A	T	5: 24,204,956 (GRCm39)	W12R	probably damaging	Het
Kansl1l	T	C	1: 66,762,437 (GRCm39)	H810R	possibly damaging	Het
Lypd1	T	C	1: 125,838,196 (GRCm39)	E41G	probably damaging	Het
Mgam	A	G	6: 40,724,853 (GRCm39)	Y443C	probably damaging	Het
Muc2	A	G	7: 141,284,976 (GRCm39)	D871G	probably damaging	Het
Nup85	T	A	11: 115,471,769 (GRCm39)	Y198N	probably damaging	Het
Obscn	T	A	11: 58,923,744 (GRCm39)	M6578L	possibly damaging	Het
Or8h7	T	C	2: 86,721,091 (GRCm39)	T143A	probably benign	Het
Osbpl5	G	C	7: 143,248,065 (GRCm39)	Q667E	probably damaging	Het
Ovgp1	T	A	3: 105,894,189 (GRCm39)		probably benign	Het
Prl8a2	T	A	13: 27,532,900 (GRCm39)	N37K	probably benign	Het
Ptprf	A	T	4: 118,126,474 (GRCm39)	I93N	possibly damaging	Het
Rnf112	T	C	11: 61,341,215 (GRCm39)	S457G	probably null	Het
Sema3e	A	G	5: 14,290,601 (GRCm39)	D562G	probably damaging	Het
Sesn3	A	G	9: 14,236,937 (GRCm39)	M472V	probably damaging	Het
Sfpq	GCCGCCGCAGCAGCCTCCGCCGCAGCAGCC	GCCGCCGCAGCAGCC	4: 126,915,419 (GRCm39)		probably benign	Het
Shc3	T	C	13: 51,620,595 (GRCm39)	T144A	probably damaging	Het
Sis	A	G	3: 72,826,818 (GRCm39)	L1287P	probably damaging	Het
Srrm2	C	T	17: 24,039,337 (GRCm39)	P2090S	probably damaging	Het
Syne2	T	G	12: 76,042,760 (GRCm39)	D3910E	possibly damaging	Het
Tcaim	C	T	9: 122,663,839 (GRCm39)	T443I	probably benign	Het
Tex19.1	T	C	11: 121,037,948 (GRCm39)	V102A	probably benign	Het
Tpd52l1	T	G	10: 31,208,950 (GRCm39)	T168P	possibly damaging	Het
Trdn	G	A	10: 33,109,944 (GRCm39)	C294Y	probably benign	Het
Trmt1l	T	C	1: 151,327,926 (GRCm39)	Y479H	probably benign	Het
Vmn1r171	G	A	7: 23,331,804 (GRCm39)	V10I	probably benign	Het
Zbtb41	T	A	1: 139,351,128 (GRCm39)	D80E	possibly damaging	Het
Zcchc4	A	G	5: 52,980,976 (GRCm39)	K473E	possibly 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
R6511:Lrp5	UTSW	19	3,702,296 (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
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'- AGTGAAACACCCTTCTGGAC -3'
(R):5'- GGTGCTGATAAAGAGGAGCCTC -3'

Sequencing Primer
(F):5'- AAGCCCACGTCTGATCCTG -3'
(R):5'- CTCTGGGGCAACTTGAGC -3'

Posted On

2018-11-06