Mutagenetix > Incidental Mutation

Incidental Mutation 'R0440:Lrp8'

46678

Institutional Source

Beutler Lab

Gene Symbol

Lrp8

Ensembl Gene

ENSMUSG00000028613

Gene Name

low density lipoprotein receptor-related protein 8, apolipoprotein e receptor

Synonyms

Lr8b, 4932703M08Rik, apoER2

MMRRC Submission

038641-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.402) question?

Stock #

R0440 (G1)

Quality Score

225

Status

Validated (trace)

Chromosome

Chromosomal Location

107802261-107876840 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 107869098 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glutamic Acid to Glycine at position 908 (E908G)

Ref Sequence

ENSEMBL: ENSMUSP00000115854 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000030356] [ENSMUST00000106732] [ENSMUST00000106733] [ENSMUST00000126573] [ENSMUST00000143601]

AlphaFold

Q924X6

Predicted Effect

possibly damaging
Transcript: ENSMUST00000030356
AA Change: E867G

PolyPhen 2 Score 0.550 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000030356
Gene: ENSMUSG00000028613
AA Change: E867G

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
LDLa	40	77	3.24e-13	SMART
EGF_like	79	117	3.29e1	SMART
LDLa	79	118	2.45e-13	SMART
LDLa	120	159	1.19e-11	SMART
LDLa	160	197	3.52e-14	SMART
LDLa	199	239	8.09e-14	SMART
LDLa	250	288	4.05e-14	SMART
LDLa	290	327	4.58e-13	SMART
EGF	331	367	2.83e-5	SMART
EGF_CA	368	407	9.91e-10	SMART
LY	434	476	8.44e-4	SMART
LY	481	523	2.29e-14	SMART
LY	524	567	5.96e-13	SMART
LY	568	610	4.21e-13	SMART
LY	612	654	7.24e-3	SMART
EGF	681	727	1.56e1	SMART
low complexity region	729	745	N/A	INTRINSIC
low complexity region	783	798	N/A	INTRINSIC
transmembrane domain	818	840	N/A	INTRINSIC
low complexity region	863	869	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000106731
AA Change: E669G

PolyPhen 2 Score 0.201 (Sensitivity: 0.92; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000102342
Gene: ENSMUSG00000028613
AA Change: E669G

Domain	Start	End	E-Value	Type
EGF_like	9	47	3.29e1	SMART
LDLa	9	48	2.45e-13	SMART
LDLa	50	89	1.19e-11	SMART
LDLa	93	130	4.58e-13	SMART
EGF	134	170	2.83e-5	SMART
EGF_CA	171	210	9.91e-10	SMART
LY	237	279	8.44e-4	SMART
LY	284	326	2.29e-14	SMART
LY	327	370	5.96e-13	SMART
LY	371	413	4.21e-13	SMART
LY	415	457	7.24e-3	SMART
EGF	484	530	1.56e1	SMART
low complexity region	532	548	N/A	INTRINSIC
low complexity region	586	601	N/A	INTRINSIC
transmembrane domain	621	643	N/A	INTRINSIC
low complexity region	666	672	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000106732
AA Change: E782G

PolyPhen 2 Score 0.888 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000102343
Gene: ENSMUSG00000028613
AA Change: E782G

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
LDLa	40	77	3.24e-13	SMART
EGF_like	79	117	3.29e1	SMART
LDLa	79	118	2.45e-13	SMART
LDLa	120	159	1.19e-11	SMART
LDLa	164	201	4.58e-13	SMART
LDLa	204	244	1.4e-8	SMART
EGF	246	282	2.83e-5	SMART
EGF_CA	283	322	9.91e-10	SMART
LY	349	391	8.44e-4	SMART
LY	396	438	2.29e-14	SMART
LY	439	482	5.96e-13	SMART
LY	483	525	4.21e-13	SMART
LY	527	569	7.24e-3	SMART
EGF	596	642	1.56e1	SMART
low complexity region	644	660	N/A	INTRINSIC
low complexity region	698	713	N/A	INTRINSIC
transmembrane domain	733	755	N/A	INTRINSIC
low complexity region	778	784	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000106733
AA Change: E867G

PolyPhen 2 Score 0.977 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000102344
Gene: ENSMUSG00000028613
AA Change: E867G

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
LDLa	40	77	3.24e-13	SMART
EGF_like	79	117	3.29e1	SMART
LDLa	79	118	2.45e-13	SMART
LDLa	120	159	1.19e-11	SMART
LDLa	160	197	3.52e-14	SMART
LDLa	199	239	8.09e-14	SMART
LDLa	250	288	4.05e-14	SMART
LDLa	290	327	4.58e-13	SMART
EGF	331	367	2.83e-5	SMART
EGF_CA	368	407	9.91e-10	SMART
LY	434	476	8.44e-4	SMART
LY	481	523	2.29e-14	SMART
LY	524	567	5.96e-13	SMART
LY	568	610	4.21e-13	SMART
LY	612	654	7.24e-3	SMART
EGF	681	727	1.56e1	SMART
low complexity region	729	745	N/A	INTRINSIC
low complexity region	783	798	N/A	INTRINSIC
transmembrane domain	818	840	N/A	INTRINSIC
low complexity region	863	869	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000123140

Predicted Effect

possibly damaging
Transcript: ENSMUST00000126573
AA Change: E665G

PolyPhen 2 Score 0.934 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000118020
Gene: ENSMUSG00000028613
AA Change: E665G

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
LDLa	40	77	3.24e-13	SMART
EGF_like	79	117	3.29e1	SMART
LDLa	79	118	2.45e-13	SMART
LDLa	120	159	1.19e-11	SMART
LDLa	163	200	4.58e-13	SMART
EGF	204	240	2.83e-5	SMART
EGF_CA	241	280	9.91e-10	SMART
LY	307	349	8.44e-4	SMART
LY	354	396	2.29e-14	SMART
LY	397	440	5.96e-13	SMART
LY	441	483	4.21e-13	SMART
LY	485	527	7.24e-3	SMART
EGF	554	600	1.56e1	SMART
transmembrane domain	616	638	N/A	INTRINSIC
low complexity region	661	667	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000143601
AA Change: E908G

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000115854
Gene: ENSMUSG00000028613
AA Change: E908G

Domain	Start	End	E-Value	Type
signal peptide	1	27	N/A	INTRINSIC
LDLa	40	77	3.24e-13	SMART
EGF_like	79	117	3.29e1	SMART
LDLa	79	118	2.45e-13	SMART
LDLa	120	159	1.19e-11	SMART
LDLa	160	197	3.52e-14	SMART
LDLa	199	239	8.09e-14	SMART
LDLa	250	288	4.05e-14	SMART
LDLa	290	327	4.58e-13	SMART
LDLa	330	370	1.4e-8	SMART
EGF	372	408	2.83e-5	SMART
EGF_CA	409	448	9.91e-10	SMART
LY	475	517	8.44e-4	SMART
LY	522	564	2.29e-14	SMART
LY	565	608	5.96e-13	SMART
LY	609	651	4.21e-13	SMART
LY	653	695	7.24e-3	SMART
EGF	722	768	1.56e1	SMART
low complexity region	770	786	N/A	INTRINSIC
low complexity region	824	839	N/A	INTRINSIC
transmembrane domain	859	881	N/A	INTRINSIC
low complexity region	904	910	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000146552

Meta Mutation Damage Score

0.1148

Coding Region Coverage

1x: 99.6%
3x: 98.8%
10x: 97.0%
20x: 94.1%

Validation Efficiency

99% (68/69)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the low density lipoprotein receptor (LDLR) family. Low density lipoprotein receptors are cell surface proteins that play roles in both signal transduction and receptor-mediated endocytosis of specific ligands for lysosomal degradation. The encoded protein plays a critical role in the migration of neurons during development by mediating Reelin signaling, and also functions as a receptor for the cholesterol transport protein apolipoprotein E. Expression of this gene may be a marker for major depressive disorder. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2011]
PHENOTYPE: Homozygotes for a targeted null mutation exhibit impaired granule cell migration, radial glial scaffold formation, contextual fear conditioning, and long-term potentiation. Mutant males have abnormal sperm and are sterile. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 67 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A4galt	G	A	15: 83,228,493	R30W	probably damaging	Het
Adam7	T	C	14: 68,510,856		probably null	Het
Agl	A	T	3: 116,758,806	L1158Q	probably damaging	Het
Akap9	T	C	5: 4,064,569	S66P	probably damaging	Het
Akr1c20	T	A	13: 4,487,208	D316V	probably benign	Het
App	C	A	16: 85,056,414	E259*	probably null	Het
Arhgef4	A	G	1: 34,745,448		probably null	Het
Armc9	G	A	1: 86,194,262		probably null	Het
Ass1	A	T	2: 31,514,819	N371Y	probably damaging	Het
Btaf1	C	T	19: 36,986,653	P875S	probably damaging	Het
Cc2d1b	T	A	4: 108,625,816		probably null	Het
Ccar1	C	T	10: 62,780,457	V165I	possibly damaging	Het
Ccdc106	A	T	7: 5,060,245	I250F	probably damaging	Het
Ccny	T	C	18: 9,332,917	I205V	probably benign	Het
Cfap52	T	A	11: 67,954,088	I52L	probably benign	Het
Chd8	T	A	14: 52,204,826	T2096S	possibly damaging	Het
Clstn3	G	A	6: 124,451,413	T423I	probably damaging	Het
Col13a1	T	C	10: 61,867,483	D440G	possibly damaging	Het
Dclk3	G	A	9: 111,469,163	V592M	probably damaging	Het
Ddx31	A	T	2: 28,857,132	I208F	probably damaging	Het
Dlat	A	T	9: 50,645,119		probably null	Het
Eml4	T	C	17: 83,446,058		probably null	Het
Enpp2	T	A	15: 54,847,237		probably benign	Het
Fryl	T	C	5: 73,086,972	S38G	possibly damaging	Het
Gcnt1	G	A	19: 17,330,316	T15I	probably benign	Het
Gm21834	T	C	17: 57,742,126	T32A	possibly damaging	Het
Golga2	A	G	2: 32,302,933	D394G	probably damaging	Het
Gtf3c4	G	T	2: 28,840,169		probably null	Het
Igkv4-69	A	G	6: 69,284,269		probably benign	Het
Inpp5j	T	C	11: 3,501,150	R500G	possibly damaging	Het
Kif5b	A	T	18: 6,226,980		probably benign	Het
Klhl36	A	G	8: 119,876,551	E515G	probably damaging	Het
Lifr	C	T	15: 7,157,191	R59*	probably null	Het
Lrif1	A	T	3: 106,734,398	Q10L	possibly damaging	Het
Lrrc23	A	T	6: 124,770,704	D307E	probably benign	Het
Mpv17l	T	C	16: 13,944,719	F27L	probably damaging	Het
Mta3	C	T	17: 83,766,587	A76V	probably damaging	Het
Muc5ac	T	A	7: 141,792,034	Y202*	probably null	Het
Naprt	A	G	15: 75,891,069		probably benign	Het
Npr2	T	A	4: 43,650,315	V960D	probably damaging	Het
Oca2	A	T	7: 56,423,352	Y765F	probably benign	Het
Olfr715	A	T	7: 107,128,732	H220Q	probably benign	Het
Plxna2	T	A	1: 194,644,404	Y215*	probably null	Het
Prdm16	G	A	4: 154,476,627		probably benign	Het
Ptn	A	G	6: 36,744,497	S3P	probably benign	Het
Pus10	T	C	11: 23,673,331		probably benign	Het
Rad21	A	T	15: 51,968,358	D442E	probably benign	Het
Rmdn2	A	G	17: 79,667,955	H291R	probably damaging	Het
Rp1	A	G	1: 4,345,640	S1750P	probably damaging	Het
Samd4b	A	T	7: 28,408,160	I228N	probably benign	Het
Sdr9c7	G	T	10: 127,898,953		probably benign	Het
Slc13a2	T	C	11: 78,403,175	N254D	probably benign	Het
Slc16a8	T	A	15: 79,252,607	I132F	probably damaging	Het
Slc18b1	T	A	10: 23,819,078	Y274N	probably benign	Het
Slc45a2	A	T	15: 11,000,817	M1L	probably benign	Het
Smc1b	A	G	15: 85,112,673		probably benign	Het
Stab2	T	C	10: 86,949,928	S617G	probably benign	Het
Stk10	A	G	11: 32,604,190	M626V	probably damaging	Het
Synpo2l	T	G	14: 20,661,398	I385L	possibly damaging	Het
Tmprss11d	T	C	5: 86,338,812	Y73C	probably damaging	Het
Ttc21b	A	G	2: 66,236,382	V309A	probably benign	Het
Tubgcp6	A	G	15: 89,103,065	I1235T	probably benign	Het
Usp8	A	G	2: 126,725,390	I110V	probably benign	Het
Vps13c	G	A	9: 67,972,861	G3442S	probably damaging	Het
Wdr59	GGGTGGTG	GGGTG	8: 111,480,540		probably benign	Het
Zfp207	T	A	11: 80,395,507		probably benign	Het
Zfp748	A	C	13: 67,553,025		probably null	Het

Other mutations in Lrp8

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01308:Lrp8	APN	4	107864076	missense	probably benign	0.04
IGL01514:Lrp8	APN	4	107855684	missense	probably damaging	1.00
IGL02058:Lrp8	APN	4	107870109	missense	probably benign	0.25
IGL02398:Lrp8	APN	4	107847494	missense	probably damaging	0.97
IGL02398:Lrp8	APN	4	107869048	missense	probably damaging	1.00
IGL02706:Lrp8	APN	4	107803319	nonsense	probably null
IGL02754:Lrp8	APN	4	107834755	splice site	probably null
IGL02967:Lrp8	APN	4	107861234	missense	probably benign	0.21
IGL03080:Lrp8	APN	4	107855799	missense	probably damaging	1.00
IGL02837:Lrp8	UTSW	4	107861281	missense	probably benign	0.01
R0312:Lrp8	UTSW	4	107806855	intron	probably benign
R0598:Lrp8	UTSW	4	107857237	missense	possibly damaging	0.73
R1627:Lrp8	UTSW	4	107854416	missense	probably damaging	0.99
R1967:Lrp8	UTSW	4	107859971	missense	probably damaging	1.00
R2183:Lrp8	UTSW	4	107803265	missense	probably damaging	1.00
R2208:Lrp8	UTSW	4	107855790	missense	probably damaging	1.00
R2325:Lrp8	UTSW	4	107864009	missense	probably benign	0.03
R3712:Lrp8	UTSW	4	107848302	missense	probably benign	0.08
R4093:Lrp8	UTSW	4	107843271	nonsense	probably null
R4706:Lrp8	UTSW	4	107861273	missense	probably benign	0.00
R4765:Lrp8	UTSW	4	107854395	missense	probably damaging	1.00
R4840:Lrp8	UTSW	4	107870037	missense	possibly damaging	0.79
R4900:Lrp8	UTSW	4	107806809	intron	probably benign
R5033:Lrp8	UTSW	4	107834755	splice site	probably null
R5280:Lrp8	UTSW	4	107854321	missense	probably damaging	1.00
R5381:Lrp8	UTSW	4	107869110	missense	probably damaging	1.00
R5935:Lrp8	UTSW	4	107857296	missense	probably damaging	1.00
R5972:Lrp8	UTSW	4	107869070	missense	probably damaging	1.00
R6076:Lrp8	UTSW	4	107847459	missense	possibly damaging	0.81
R6343:Lrp8	UTSW	4	107869156	splice site	probably null
R6805:Lrp8	UTSW	4	107854320	missense	probably damaging	0.99
R7100:Lrp8	UTSW	4	107802450	missense	possibly damaging	0.93
R7262:Lrp8	UTSW	4	107847464	missense	probably benign
R7717:Lrp8	UTSW	4	107834743	missense	probably benign	0.00
R7949:Lrp8	UTSW	4	107803327	missense	probably damaging	1.00
R8350:Lrp8	UTSW	4	107847464	missense	probably benign
R8371:Lrp8	UTSW	4	107869071	missense	probably damaging	1.00
R9272:Lrp8	UTSW	4	107859961	missense	probably benign	0.19
R9461:Lrp8	UTSW	4	107843318	missense	possibly damaging	0.93
R9567:Lrp8	UTSW	4	107854272	missense	probably damaging	0.99
Z1177:Lrp8	UTSW	4	107843332	missense	probably benign	0.02

Predicted Primers

PCR Primer
(F):5'- CAGTGGTGACTCAAAATGGAGCCC -3'
(R):5'- AGAGCCAAAACAGTGCCTGGTATG -3'

Sequencing Primer
(F):5'- CCCGGAAGCAAGGGGTTATAC -3'
(R):5'- gtgcctggtatgcaggag -3'

Posted On

2013-06-11