Mutagenetix > Incidental Mutation

Incidental Mutation 'R7717:Lrp8'

594964

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

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.360) question?

Stock #

R7717 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

107802261-107876840 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 107834743 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 115 (T115A)

Ref Sequence

ENSEMBL: ENSMUSP00000102343 (fasta)

Gene Model

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

AlphaFold

Q924X6

Predicted Effect

probably benign
Transcript: ENSMUST00000030356
AA Change: T115A

PolyPhen 2 Score 0.001 (Sensitivity: 0.99; Specificity: 0.15)

SMART Domains

Protein: ENSMUSP00000030356
Gene: ENSMUSG00000028613
AA Change: T115A

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: T44A

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000102342
Gene: ENSMUSG00000028613
AA Change: T44A

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 benign
Transcript: ENSMUST00000106732
AA Change: T115A

PolyPhen 2 Score 0.003 (Sensitivity: 0.98; Specificity: 0.44)

SMART Domains

Protein: ENSMUSP00000102343
Gene: ENSMUSG00000028613
AA Change: T115A

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 benign
Transcript: ENSMUST00000106733
AA Change: T115A

PolyPhen 2 Score 0.008 (Sensitivity: 0.96; Specificity: 0.76)

SMART Domains

Protein: ENSMUSP00000102344
Gene: ENSMUSG00000028613
AA Change: T115A

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: ENSMUST00000126573
AA Change: T115A

PolyPhen 2 Score 0.126 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000118020
Gene: ENSMUSG00000028613
AA Change: T115A

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 benign
Transcript: ENSMUST00000143601
AA Change: T115A

PolyPhen 2 Score 0.017 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000115854
Gene: ENSMUSG00000028613
AA Change: T115A

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.2%

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: 45 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
0610010F05Rik	A	C	11: 23,606,757	C408G	probably benign	Het
Adgrf5	T	C	17: 43,450,753	L1113P	probably damaging	Het
Aldh3b3	T	C	19: 3,963,970	L57P	probably damaging	Het
Asb15	A	G	6: 24,559,252	D132G	probably benign	Het
Cep290	C	T	10: 100,492,681	R111W	probably benign	Het
Cfap44	A	G	16: 44,429,935	D792G	probably damaging	Het
Col20a1	C	T	2: 181,007,615	R1029W	probably damaging	Het
Csf3r	A	G	4: 126,037,610	Y462C	probably damaging	Het
Cthrc1	T	C	15: 39,077,116	V38A	probably benign	Het
Cxcr2	T	C	1: 74,158,839	V164A	probably benign	Het
D230025D16Rik	C	A	8: 105,251,604	Q397K	probably benign	Het
Efr3b	A	G	12: 3,984,574	S199P	probably damaging	Het
Elavl4	A	G	4: 110,206,466	C342R	probably damaging	Het
Gemin5	A	T	11: 58,151,530		probably null	Het
Gm14190	A	T	11: 99,690,650	C31S	unknown	Het
Golt1b	T	A	6: 142,394,043	V78D	probably damaging	Het
Gsdmc3	T	A	15: 63,869,212	D29V	probably damaging	Het
Itih1	T	A	14: 30,931,185	D766V	probably damaging	Het
Larp1b	C	T	3: 40,972,444	S251F	probably damaging	Het
Lrrc37a	A	G	11: 103,504,300	S100P	probably benign	Het
Lss	T	C	10: 76,545,452	V424A	possibly damaging	Het
Ltbp1	T	C	17: 75,290,078	V568A	possibly damaging	Het
Myo10	A	T	15: 25,731,970	T311S	probably benign	Het
Nsd3	T	C	8: 25,682,562	V779A	probably benign	Het
Olfr1335	A	T	4: 118,808,933	S310R	probably damaging	Het
Olfr138	C	A	17: 38,275,580	Q270K	probably damaging	Het
Olfr1444	A	T	19: 12,861,795	I7F	probably benign	Het
Olfr624	T	C	7: 103,670,945	T29A	probably benign	Het
Olfr698	A	G	7: 106,752,636	W251R	possibly damaging	Het
Olfr748	T	A	14: 50,710,762	L144Q	probably damaging	Het
Pak1	T	A	7: 97,886,348	D215E	probably benign	Het
Pde7b	A	G	10: 20,407,191	F355L	probably benign	Het
Pi4ka	A	G	16: 17,376,923	S204P		Het
Pirb	T	C	7: 3,717,783	K239E	not run	Het
Pirb	C	T	7: 3,717,801	G233R	not run	Het
Pnp	G	A	14: 50,951,003	M211I	probably benign	Het
Pot1a	A	T	6: 25,758,823	L319Q	probably benign	Het
Rspry1	G	T	8: 94,623,122	C46F	probably damaging	Het
Sec11c	C	T	18: 65,812,712	T82M	possibly damaging	Het
Secisbp2	T	C	13: 51,673,098	V414A	probably benign	Het
Tenm2	A	G	11: 36,864,935	F79L	probably damaging	Het
Vmn2r2	A	G	3: 64,134,598	V232A	possibly damaging	Het
Zbtb17	T	C	4: 141,466,083	S593P	probably damaging	Het
Zfp143	T	G	7: 110,086,220	C419G	possibly damaging	Het
Zfp804b	T	C	5: 6,771,293	N590S	possibly damaging	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
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
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'- CTCTGTCTTAGAAAAGCATTCAGTGC -3'
(R):5'- TCTAATTCCTGGTGCTGCAGG -3'

Sequencing Primer
(F):5'- ATTCAGTGCTCACCCTTATGC -3'
(R):5'- ACCTACAGGGAAGCTCAGG -3'

Posted On

2019-11-12