Mutagenetix > Incidental Mutation

Incidental Mutation 'R2117:Npc1'

231137

Institutional Source

Beutler Lab

Gene Symbol

Npc1

Ensembl Gene

ENSMUSG00000024413

Gene Name

NPC intracellular cholesterol transporter 1

Synonyms

lcsd, nmf164, D18Ertd139e, D18Ertd723e, A430089E03Rik, C85354

MMRRC Submission

040121-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.616) question?

Stock #

R2117 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

12322749-12369457 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 12329613 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Proline to Leucine at position 990 (P990L)

Ref Sequence

ENSEMBL: ENSMUSP00000025279 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000025279]

AlphaFold

O35604

Predicted Effect

probably damaging
Transcript: ENSMUST00000025279
AA Change: P990L

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

SMART Domains

Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: P990L

Domain	Start	End	E-Value	Type
low complexity region	8	15	N/A	INTRINSIC
Pfam:NPC1_N	22	267	1.6e-79	PFAM
transmembrane domain	269	291	N/A	INTRINSIC
transmembrane domain	353	375	N/A	INTRINSIC
Pfam:Patched	436	896	3.5e-52	PFAM
Pfam:MMPL	648	794	6.3e-8	PFAM
Pfam:Sterol-sensing	649	803	2.7e-56	PFAM
Pfam:Patched	1023	1252	2.9e-33	PFAM
low complexity region	1259	1273	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000153352

Coding Region Coverage

1x: 99.1%
3x: 98.5%
10x: 97.2%
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 large protein that resides in the limiting membrane of endosomes and lysosomes and mediates intracellular cholesterol trafficking via binding of cholesterol to its N-terminal domain. It is predicted to have a cytoplasmic C-terminus, 13 transmembrane domains, and 3 large loops in the lumen of the endosome - the last loop being at the N-terminus. This protein transports low-density lipoproteins to late endosomal/lysosomal compartments where they are hydrolized and released as free cholesterol. Defects in this gene cause Niemann-Pick type C disease, a rare autosomal recessive neurodegenerative disorder characterized by over accumulation of cholesterol and glycosphingolipids in late endosomal/lysosomal compartments.[provided by RefSeq, Aug 2009]
PHENOTYPE: Homozygotes for spontaneous and chemically induced mutations may exhibit lysosomal storage of non-esterified cholesterol, neurodegeneration, ataxia, presence of foam cells, sterility, and shortened lifespan. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 101 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adgrv1	A	T	13: 81,640,656 (GRCm39)	C3357S	probably benign	Het
Ago1	T	A	4: 126,357,650 (GRCm39)		probably null	Het
Akap10	A	T	11: 61,781,129 (GRCm39)	D562E	possibly damaging	Het
Akr1b7	G	A	6: 34,395,929 (GRCm39)	A144T	possibly damaging	Het
Ankle1	A	G	8: 71,860,562 (GRCm39)	T340A	probably benign	Het
Arf5	C	T	6: 28,424,783 (GRCm39)	Q71*	probably null	Het
Arl15	C	T	13: 114,104,196 (GRCm39)	S111F	probably damaging	Het
Asph	G	A	4: 9,517,671 (GRCm39)	Q468*	probably null	Het
Bcam	G	T	7: 19,492,352 (GRCm39)	A581E	possibly damaging	Het
Blvra	G	T	2: 126,927,989 (GRCm39)	E80*	probably null	Het
Ccr6	T	C	17: 8,474,914 (GRCm39)	F40L	possibly damaging	Het
Cfap161	A	T	7: 83,425,184 (GRCm39)	N302K	possibly damaging	Het
Ckmt2	T	A	13: 92,003,964 (GRCm39)	I345F	probably benign	Het
Cpsf6	A	G	10: 117,202,025 (GRCm39)		probably benign	Het
Ctnna1	A	G	18: 35,285,678 (GRCm39)	N8S	possibly damaging	Het
Cyp2d11	A	G	15: 82,275,954 (GRCm39)	L209P	probably damaging	Het
Dab2	T	C	15: 6,465,096 (GRCm39)	V628A	probably damaging	Het
Dcstamp	C	T	15: 39,618,571 (GRCm39)	Q327*	probably null	Het
Defb38	A	T	8: 19,073,483 (GRCm39)	Y63*	probably null	Het
Dlg5	A	T	14: 24,227,826 (GRCm39)	L365*	probably null	Het
Dnai7	C	T	6: 145,150,967 (GRCm39)		probably null	Het
Dnmt3l	C	A	10: 77,899,130 (GRCm39)	L110I	probably damaging	Het
Exoc3l2	G	T	7: 19,228,907 (GRCm39)	L108F	possibly damaging	Het
Exoc4	T	A	6: 33,324,760 (GRCm39)	N351K	possibly damaging	Het
Fam83h	C	A	15: 75,876,582 (GRCm39)	E252*	probably null	Het
Fancm	A	G	12: 65,123,948 (GRCm39)	D202G	probably damaging	Het
Fat1	T	A	8: 45,490,500 (GRCm39)	V3804E	probably benign	Het
Fbxw28	T	C	9: 109,159,985 (GRCm39)	T190A	probably benign	Het
Fer1l4	T	C	2: 155,881,038 (GRCm39)	T843A	probably benign	Het
Fnip1	A	T	11: 54,391,450 (GRCm39)	H461L	probably damaging	Het
Gcn1	A	T	5: 115,736,884 (GRCm39)	M1276L	probably benign	Het
Gemin4	A	G	11: 76,101,827 (GRCm39)	V978A	possibly damaging	Het
Gm7247	A	T	14: 51,602,792 (GRCm39)	I43F	probably damaging	Het
Gm9978	C	T	10: 78,322,731 (GRCm39)		noncoding transcript	Het
Gpr4	T	C	7: 18,957,070 (GRCm39)	S331P	probably damaging	Het
Hspa1a	T	A	17: 35,189,455 (GRCm39)	N483Y	probably damaging	Het
Ift74	A	G	4: 94,515,496 (GRCm39)	T138A	probably benign	Het
Ints14	T	G	9: 64,887,077 (GRCm39)	L336R	probably damaging	Het
Irak1	G	T	X: 73,066,218 (GRCm39)	P197Q	possibly damaging	Het
Kif4	A	G	X: 99,709,323 (GRCm39)	S315G	probably benign	Het
L3mbtl1	T	A	2: 162,801,990 (GRCm39)		probably null	Het
Lamb3	A	G	1: 193,016,489 (GRCm39)	R657G	probably benign	Het
Ldc1	C	A	4: 130,109,156 (GRCm39)	V295L	possibly damaging	Het
Lrp2	A	C	2: 69,313,729 (GRCm39)	V2334G	probably benign	Het
Lrwd1	T	A	5: 136,159,332 (GRCm39)	Y431F	probably damaging	Het
Map3k21	A	T	8: 126,650,781 (GRCm39)	H261L	probably benign	Het
Meis1	G	T	11: 18,831,679 (GRCm39)	P453Q	probably damaging	Het
Mettl16	G	T	11: 74,693,755 (GRCm39)	M255I	probably benign	Het
Mllt10	A	G	2: 18,167,380 (GRCm39)	N435S	probably benign	Het
Mta2	T	C	19: 8,920,880 (GRCm39)	I27T	probably damaging	Het
Nav2	A	G	7: 49,114,328 (GRCm39)	I771V	probably benign	Het
Nisch	A	T	14: 30,899,242 (GRCm39)		probably benign	Het
Nrxn1	A	T	17: 91,011,705 (GRCm39)	I308K	probably damaging	Het
Or13l2	C	A	3: 97,317,765 (GRCm39)	C244F	probably damaging	Het
Or1ad6	A	T	11: 50,860,147 (GRCm39)	I101F	probably damaging	Het
Or5h17	T	C	16: 58,820,783 (GRCm39)	L245P	possibly damaging	Het
Otogl	T	C	10: 107,694,779 (GRCm39)	D823G	probably benign	Het
P2rx7	A	G	5: 122,819,329 (GRCm39)	T584A	probably benign	Het
Pals1	T	C	12: 78,856,696 (GRCm39)	F180L	possibly damaging	Het
Pank1	T	A	19: 34,818,486 (GRCm39)	I18F	probably damaging	Het
Pgap3	A	G	11: 98,281,933 (GRCm39)	L126P	probably damaging	Het
Pgap6	C	T	17: 26,336,858 (GRCm39)	L259F	possibly damaging	Het
Phka1	C	T	X: 101,653,807 (GRCm39)	R290H	probably damaging	Het
Pkd2	G	A	5: 104,631,042 (GRCm39)	E489K	probably damaging	Het
Prdm16	T	A	4: 154,432,382 (GRCm39)	S296C	probably null	Het
Prex2	T	A	1: 11,256,937 (GRCm39)	N1216K	probably damaging	Het
Prmt7	A	G	8: 106,953,930 (GRCm39)	T124A	probably damaging	Het
Ptpra	G	T	2: 130,381,655 (GRCm39)	R372L	probably damaging	Het
Ptpro	T	A	6: 137,420,592 (GRCm39)	V1007D	probably damaging	Het
Rap2b	G	T	3: 61,272,512 (GRCm39)	G12V	probably damaging	Het
Rapgef5	T	A	12: 117,677,799 (GRCm39)		probably null	Het
Rassf4	A	G	6: 116,622,088 (GRCm39)	F168S	possibly damaging	Het
Rtf1	T	A	2: 119,535,999 (GRCm39)	H184Q	probably benign	Het
Sacs	A	G	14: 61,451,220 (GRCm39)	K4422R	probably benign	Het
Sec11c	A	T	18: 65,933,720 (GRCm39)	T9S	probably benign	Het
Sema3d	C	T	5: 12,613,240 (GRCm39)	T439I	probably benign	Het
Sephs1	A	G	2: 4,904,351 (GRCm39)	N243S	probably benign	Het
Setd2	TTGGGA	T	9: 110,433,212 (GRCm39)		probably null	Het
Setx	A	G	2: 29,020,313 (GRCm39)	D100G	probably benign	Het
Slc22a7	C	A	17: 46,744,898 (GRCm39)	V383L	possibly damaging	Het
Slc25a40	T	C	5: 8,480,417 (GRCm39)	C56R	probably damaging	Het
Stk38l	T	A	6: 146,670,344 (GRCm39)	L229I	probably damaging	Het
Sult2a5	T	C	7: 13,359,359 (GRCm39)	S112P	probably damaging	Het
Syt4	A	G	18: 31,573,520 (GRCm39)	Y332H	probably damaging	Het
Tcof1	T	C	18: 60,965,857 (GRCm39)	E415G	possibly damaging	Het
Tenm2	A	G	11: 35,915,681 (GRCm39)	L1951P	probably damaging	Het
Tlr9	A	G	9: 106,102,536 (GRCm39)	N609S	probably damaging	Het
Tmem120a	A	T	5: 135,764,977 (GRCm39)	S266T	possibly damaging	Het
Tmem132b	A	G	5: 125,699,615 (GRCm39)	E92G	probably damaging	Het
Tnfrsf18	T	A	4: 156,112,973 (GRCm39)	V196E	probably damaging	Het
Trpc1	A	T	9: 95,599,637 (GRCm39)	L474H	probably damaging	Het
Trpm6	T	C	19: 18,807,316 (GRCm39)	V1020A	probably damaging	Het
Usp20	T	A	2: 30,906,317 (GRCm39)	C562S	probably damaging	Het
Usp47	T	A	7: 111,666,443 (GRCm39)		probably null	Het
Vgll1	A	C	X: 56,137,790 (GRCm39)	K53T	probably damaging	Het
Vmn1r26	T	C	6: 57,985,335 (GRCm39)	N285D	possibly damaging	Het
Zfp445	T	A	9: 122,682,502 (GRCm39)	K480*	probably null	Het
Zfp786	A	G	6: 47,803,931 (GRCm39)	V37A	probably damaging	Het
Zfp821	A	G	8: 110,447,851 (GRCm39)	E64G	probably damaging	Het
Zfp994	T	A	17: 22,419,962 (GRCm39)	D329V	probably damaging	Het
Zkscan8	T	C	13: 21,704,488 (GRCm39)	S484G	probably damaging	Het

Other mutations in Npc1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02347:Npc1	APN	18	12,332,691 (GRCm39)	missense	probably benign	0.45
IGL02523:Npc1	APN	18	12,334,629 (GRCm39)	missense	probably benign	0.00
IGL03018:Npc1	APN	18	12,347,436 (GRCm39)	missense	probably damaging	0.99
IGL03101:Npc1	APN	18	12,331,596 (GRCm39)	missense	probably benign	0.15
IGL03151:Npc1	APN	18	12,352,332 (GRCm39)	missense	probably benign	0.05
IGL03377:Npc1	APN	18	12,344,878 (GRCm39)	missense	probably benign
PIT4354001:Npc1	UTSW	18	12,344,592 (GRCm39)	missense	probably benign	0.00
R0068:Npc1	UTSW	18	12,341,424 (GRCm39)	missense	probably benign	0.04
R0068:Npc1	UTSW	18	12,341,424 (GRCm39)	missense	probably benign	0.04
R0190:Npc1	UTSW	18	12,324,887 (GRCm39)	missense	probably damaging	1.00
R0200:Npc1	UTSW	18	12,352,261 (GRCm39)	missense	probably damaging	1.00
R0485:Npc1	UTSW	18	12,346,503 (GRCm39)	missense	probably benign	0.00
R0699:Npc1	UTSW	18	12,343,632 (GRCm39)	missense	probably benign	0.00
R0730:Npc1	UTSW	18	12,352,382 (GRCm39)	missense	probably benign	0.00
R1302:Npc1	UTSW	18	12,328,142 (GRCm39)	missense	probably benign	0.00
R1442:Npc1	UTSW	18	12,328,106 (GRCm39)	missense	probably benign
R1463:Npc1	UTSW	18	12,324,887 (GRCm39)	missense	probably damaging	1.00
R1804:Npc1	UTSW	18	12,356,145 (GRCm39)	missense	probably damaging	1.00
R1808:Npc1	UTSW	18	12,327,149 (GRCm39)	missense	probably damaging	1.00
R1928:Npc1	UTSW	18	12,346,435 (GRCm39)	missense	possibly damaging	0.79
R2112:Npc1	UTSW	18	12,346,529 (GRCm39)	missense	possibly damaging	0.49
R2157:Npc1	UTSW	18	12,324,866 (GRCm39)	missense	probably damaging	0.98
R2279:Npc1	UTSW	18	12,330,236 (GRCm39)	splice site	probably null
R2311:Npc1	UTSW	18	12,335,240 (GRCm39)	missense	probably benign
R2446:Npc1	UTSW	18	12,347,396 (GRCm39)	missense	probably benign	0.01
R3004:Npc1	UTSW	18	12,330,311 (GRCm39)	missense	probably benign	0.03
R4090:Npc1	UTSW	18	12,331,219 (GRCm39)	splice site	probably null
R4304:Npc1	UTSW	18	12,343,584 (GRCm39)	missense	possibly damaging	0.77
R4308:Npc1	UTSW	18	12,343,584 (GRCm39)	missense	possibly damaging	0.77
R4564:Npc1	UTSW	18	12,324,789 (GRCm39)	missense	probably damaging	1.00
R4786:Npc1	UTSW	18	12,332,554 (GRCm39)	missense	probably benign	0.35
R5243:Npc1	UTSW	18	12,331,688 (GRCm39)	intron	probably benign
R5404:Npc1	UTSW	18	12,346,356 (GRCm39)	missense	possibly damaging	0.79
R5823:Npc1	UTSW	18	12,324,846 (GRCm39)	missense	possibly damaging	0.69
R6080:Npc1	UTSW	18	12,352,408 (GRCm39)	missense	probably damaging	1.00
R6215:Npc1	UTSW	18	12,369,249 (GRCm39)	small deletion	probably benign
R6301:Npc1	UTSW	18	12,330,302 (GRCm39)	missense	probably benign	0.00
R6476:Npc1	UTSW	18	12,334,751 (GRCm39)	nonsense	probably null
R7007:Npc1	UTSW	18	12,343,605 (GRCm39)	missense	probably benign	0.02
R7020:Npc1	UTSW	18	12,331,594 (GRCm39)	missense	probably damaging	1.00
R7048:Npc1	UTSW	18	12,337,822 (GRCm39)	splice site	probably null
R7116:Npc1	UTSW	18	12,344,601 (GRCm39)	missense	probably damaging	1.00
R7153:Npc1	UTSW	18	12,346,348 (GRCm39)	missense	possibly damaging	0.78
R7359:Npc1	UTSW	18	12,328,237 (GRCm39)	missense	probably benign	0.05
R7382:Npc1	UTSW	18	12,334,763 (GRCm39)	missense	probably damaging	0.99
R7765:Npc1	UTSW	18	12,328,105 (GRCm39)	missense	probably benign	0.01
R8047:Npc1	UTSW	18	12,346,374 (GRCm39)	missense	probably benign	0.00
R8094:Npc1	UTSW	18	12,327,297 (GRCm39)	missense	probably benign
R8161:Npc1	UTSW	18	12,328,129 (GRCm39)	missense	possibly damaging	0.77
R8310:Npc1	UTSW	18	12,326,455 (GRCm39)	missense	probably damaging	0.98
R8821:Npc1	UTSW	18	12,333,877 (GRCm39)	missense	probably benign	0.01
R8831:Npc1	UTSW	18	12,333,877 (GRCm39)	missense	probably benign	0.01
R8847:Npc1	UTSW	18	12,323,987 (GRCm39)	missense	probably damaging	1.00
R9022:Npc1	UTSW	18	12,346,422 (GRCm39)	missense	probably benign
R9343:Npc1	UTSW	18	12,334,769 (GRCm39)	missense	possibly damaging	0.52
R9460:Npc1	UTSW	18	12,346,398 (GRCm39)	missense	possibly damaging	0.93
R9723:Npc1	UTSW	18	12,343,649 (GRCm39)	missense	probably benign
X0012:Npc1	UTSW	18	12,326,368 (GRCm39)	splice site	probably null

Predicted Primers

PCR Primer
(F):5'- AAACCGTGTCTCTGCCCTAC -3'
(R):5'- CCACATGGAGCTGAAGCATTTG -3'

Sequencing Primer
(F):5'- CCTACAGGACTAGGGCAGG -3'
(R):5'- TGGAGCTGAAGCATTTGAGGGG -3'

Posted On

2014-09-18