Mutagenetix > Incidental Mutation

Incidental Mutation 'R4765:Lrp8'

366047

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

042406-MU

Accession Numbers

Essential gene?

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

Stock #

R4765 (G1)

Quality Score

180

Status

Not validated

Chromosome

Chromosomal Location

107802261-107876840 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 107854395 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Cysteine to Arginine at position 459 (C459R)

Ref Sequence

ENSEMBL: ENSMUSP00000030356 (fasta)

Gene Model

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

AlphaFold

Q924X6

Predicted Effect

probably damaging
Transcript: ENSMUST00000030356
AA Change: C459R

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

SMART Domains

Protein: ENSMUSP00000030356
Gene: ENSMUSG00000028613
AA Change: C459R

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

unknown
Transcript: ENSMUST00000106731
AA Change: C261R

SMART Domains

Protein: ENSMUSP00000102342
Gene: ENSMUSG00000028613
AA Change: C261R

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

probably damaging
Transcript: ENSMUST00000106732
AA Change: C374R

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000102343
Gene: ENSMUSG00000028613
AA Change: C374R

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: C459R

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000102344
Gene: ENSMUSG00000028613
AA Change: C459R

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

probably damaging
Transcript: ENSMUST00000126573
AA Change: C332R

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000118020
Gene: ENSMUSG00000028613
AA Change: C332R

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

noncoding transcript
Transcript: ENSMUST00000135022

Predicted Effect

probably damaging
Transcript: ENSMUST00000143601
AA Change: C500R

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000115854
Gene: ENSMUSG00000028613
AA Change: C500R

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

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000147319

Coding Region Coverage

1x: 99.2%
3x: 98.5%
10x: 97.1%
20x: 95.0%

Validation Efficiency

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: 75 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2810021J22Rik	C	T	11: 58,881,161	R490C	probably benign	Het
Abcb11	A	T	2: 69,245,867	F1166I	probably damaging	Het
Acta2	T	C	19: 34,246,152	D181G	probably damaging	Het
Adgrv1	A	G	13: 81,106,919	I6195T	probably damaging	Het
Afg3l2	G	T	18: 67,421,259	L458M	probably damaging	Het
Ankfy1	T	G	11: 72,712,291	S49A	probably benign	Het
Azi2	A	T	9: 118,061,471		probably benign	Het
Bend3	A	T	10: 43,510,750	S380C	probably damaging	Het
Bicc1	T	C	10: 70,940,593	T759A	probably damaging	Het
Cdh10	G	T	15: 19,013,278	V655L	probably damaging	Het
Cdkn2aip	C	A	8: 47,713,547	W75L	probably damaging	Het
Cenpj	G	A	14: 56,549,545	R192*	probably null	Het
Cflar	T	C	1: 58,732,321	S203P	probably damaging	Het
Chd6	A	T	2: 160,966,244	C1683*	probably null	Het
Cpsf2	A	G	12: 101,997,440	Y476C	probably damaging	Het
Cyp4a12a	A	G	4: 115,326,191	D169G	possibly damaging	Het
D430041D05Rik	T	A	2: 104,214,096	R1536S	probably damaging	Het
Depdc5	A	C	5: 32,937,635	D752A	probably damaging	Het
Dnah9	C	T	11: 65,927,726	G78D	probably damaging	Het
Drc1	G	T	5: 30,348,731	Q249H	probably benign	Het
Drg1	T	C	11: 3,250,280	I364V	probably benign	Het
Dtymk	T	C	1: 93,792,909	H130R	probably damaging	Het
Elac2	T	G	11: 64,992,222	F140V	probably damaging	Het
Enpp2	A	G	15: 54,875,672	V353A	possibly damaging	Het
Fat2	T	C	11: 55,281,187	D2900G	probably damaging	Het
Fermt2	G	T	14: 45,462,236	T536K	probably benign	Het
Foxj2	G	T	6: 122,833,271	Q196H	probably benign	Het
Gadl1	A	G	9: 115,966,313	K328R	probably null	Het
Gata6	A	G	18: 11,054,394	T108A	probably benign	Het
Gm16503	G	T	4: 147,541,097	G16V	unknown	Het
Gpr37	T	G	6: 25,669,108	E579A	probably damaging	Het
Gps2	T	C	11: 69,916,361		probably benign	Het
Hcn4	A	T	9: 58,857,977	I581F	unknown	Het
Hfm1	T	A	5: 106,842,539	Y1335F	probably benign	Het
Igsf10	A	T	3: 59,329,705	S1018R	probably benign	Het
Katnal2	C	T	18: 76,977,543		probably null	Het
Kctd8	T	C	5: 69,340,848	K152E	possibly damaging	Het
Ly6l	A	T	15: 75,449,694	I48L	probably benign	Het
Megf10	A	T	18: 57,287,794	I835F	possibly damaging	Het
Mei1	A	T	15: 82,112,485	I946F	possibly damaging	Het
Mkl2	C	A	16: 13,412,594	P1048T	probably damaging	Het
Myo7b	G	C	18: 31,961,900	L1881V	probably benign	Het
Nfkbiz	T	C	16: 55,819,024		probably null	Het
Olfr142	T	A	2: 90,252,463	Y175F	probably damaging	Het
Olfr1449	T	C	19: 12,935,076	C113R	possibly damaging	Het
Pcdhgc5	T	C	18: 37,822,069	S799P	probably benign	Het
Plk4	A	G	3: 40,802,022	E97G	probably damaging	Het
Pole2	A	T	12: 69,222,052	H114Q	possibly damaging	Het
Rad9a	C	A	19: 4,200,489	V109L	probably benign	Het
Scn8a	A	G	15: 101,040,471	H1917R	probably benign	Het
Scyl2	C	T	10: 89,659,298	V304I	probably damaging	Het
Serpina3f	G	C	12: 104,219,431	E298D	probably benign	Het
Shoc2	A	G	19: 53,988,303	E208G	probably benign	Het
Sin3a	G	A	9: 57,096,803	V280I	probably benign	Het
Slc26a2	A	T	18: 61,199,486	I291N	probably damaging	Het
Slc4a7	T	G	14: 14,762,414	D600E	probably damaging	Het
Slc5a6	A	T	5: 31,038,083	F430L	possibly damaging	Het
Snx19	A	C	9: 30,440,157	Q840H	probably damaging	Het
Spast	C	A	17: 74,369,216	D340E	probably damaging	Het
Sprr4	G	A	3: 92,500,409	P29S	unknown	Het
Stk11ip	T	G	1: 75,527,155	L239R	probably damaging	Het
Thoc6	A	G	17: 23,670,888	L20P	probably damaging	Het
Tnfrsf8	A	T	4: 145,296,877	S129T	probably benign	Het
Tnrc6c	A	G	11: 117,742,927	I1284V	probably benign	Het
Ttn	A	G	2: 76,710,987	L33885P	probably damaging	Het
Ttn	T	C	2: 76,772,507	Y16711C	probably damaging	Het
Ubn2	T	A	6: 38,479,140	C501S	probably damaging	Het
Ubr1	A	T	2: 120,963,442	L87*	probably null	Het
Uhmk1	T	C	1: 170,199,901	Y320C	probably damaging	Het
Vldlr	T	C	19: 27,240,547	V465A	probably damaging	Het
Vmn1r1	C	T	1: 182,157,906	A65T	probably benign	Het
Vmn2r25	C	T	6: 123,823,223	C720Y	probably damaging	Het
Xrra1	T	C	7: 99,906,568	Y381H	probably benign	Het
Zfhx4	T	C	3: 5,400,152	L1790P	probably benign	Het
Zscan4d	T	A	7: 11,162,667	M259L	probably benign	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
R0440:Lrp8	UTSW	4	107869098	missense	probably damaging	0.99
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
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'- GGAACTTGTGTCTCTAGGCTCC -3'
(R):5'- TAGGATGTGGACTCAAGGCTG -3'

Sequencing Primer
(F):5'- TGCATTCTCCACTGACACTG -3'
(R):5'- GGACTCAAGGCTGTTTCCCTACAG -3'

Posted On

2015-12-21