Mutagenetix > Incidental Mutation

Incidental Mutation 'R0137:Npc1l1'

22052

Institutional Source

Beutler Lab

Gene Symbol

Npc1l1

Ensembl Gene

ENSMUSG00000020447

Gene Name

NPC1 like intracellular cholesterol transporter 1

Synonyms

Niemann-Pick disease, type C1, 9130221N23Rik

MMRRC Submission

038422-MU

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.082) question?

Stock #

R0137 (G1)

Quality Score

225

Status

Validated (trace)

Chromosome

Chromosomal Location

6161013-6180143 bp(-) (GRCm39)

Type of Mutation

nonsense

DNA Base Change (assembly)

T to A at 6178148 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Lysine to Stop codon at position 421 (K421*)

Ref Sequence

ENSEMBL: ENSMUSP00000004505 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000004505]

AlphaFold

no structure available at present

Predicted Effect

probably null
Transcript: ENSMUST00000004505
AA Change: K421*

SMART Domains

Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: K421*

Domain	Start	End	E-Value	Type
signal peptide	1	20	N/A	INTRINSIC
Pfam:NPC1_N	28	283	8.7e-74	PFAM
low complexity region	294	307	N/A	INTRINSIC
transmembrane domain	348	370	N/A	INTRINSIC
Pfam:Patched	385	897	4.7e-52	PFAM
Pfam:Sterol-sensing	661	815	5.7e-55	PFAM
Pfam:MMPL	665	830	2.3e-11	PFAM
Pfam:Patched	1063	1268	6.2e-34	PFAM

Meta Mutation Damage Score

0.9755

Coding Region Coverage

1x: 99.0%
3x: 98.2%
10x: 96.1%
20x: 91.8%

Validation Efficiency

95% (94/99)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a multi-pass membrane protein. It contains a conserved N-terminal Niemann-Pick C1 (NPC1) domain and a putative sterol-sensing domain (SSD) which includes a YQRL motif functioning as a plasma membrane to trans-Golgi network transport signal in other proteins. This protein takes up free cholesterol into cells through vesicular endocytosis and plays a critical role in the absorption of intestinal cholesterol. It also has the ability to transport alpha-tocopherol (vitamin E). The drug ezetimibe targets this protein and inhibits the absorption of intestinal cholesterol and alpha-tocopherol. In addition, this protein may play a critical role in regulating lipid metabolism. Polymorphic variations in this gene are associated with plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) risk. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
PHENOTYPE: Mice homozygous for a targeted null mutation exhibit normal intestinal development, fertility and plasma cholesterol and triglyceride levels; however, intestinal cholesterol absorption was substantially reduced. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 91 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
6430548M08Rik	A	T	8: 120,878,115 (GRCm39)	H190L	possibly damaging	Het
Adap1	A	G	5: 139,278,976 (GRCm39)		probably benign	Het
Adgra3	C	T	5: 50,121,182 (GRCm39)		probably benign	Het
Adgre5	A	T	8: 84,451,527 (GRCm39)	V527E	probably damaging	Het
Anapc5	A	T	5: 122,938,695 (GRCm39)	Y360N	probably damaging	Het
Angptl6	C	A	9: 20,789,683 (GRCm39)	A70S	probably benign	Het
Ankdd1a	C	A	9: 65,417,610 (GRCm39)	K137N	probably null	Het
Ccdc170	T	C	10: 4,496,950 (GRCm39)		probably benign	Het
Ccdc51	A	G	9: 108,920,698 (GRCm39)	E195G	probably damaging	Het
Cdc37	A	T	9: 21,053,426 (GRCm39)	C204S	possibly damaging	Het
Cfap36	T	C	11: 29,172,431 (GRCm39)		probably benign	Het
Col6a2	C	A	10: 76,432,259 (GRCm39)	G965C	probably damaging	Het
Csn1s2a	G	A	5: 87,926,826 (GRCm39)	S53N	possibly damaging	Het
Dab2ip	T	C	2: 35,582,388 (GRCm39)		probably null	Het
Dhx58	A	G	11: 100,587,823 (GRCm39)	V578A	probably damaging	Het
Diaph1	G	T	18: 38,024,902 (GRCm39)	Q520K	unknown	Het
Eefsec	C	A	6: 88,274,631 (GRCm39)	K444N	probably benign	Het
Eftud2	A	T	11: 102,759,443 (GRCm39)	H153Q	possibly damaging	Het
Eif5b	T	G	1: 38,058,324 (GRCm39)	S209A	probably benign	Het
Exosc2	T	A	2: 31,562,497 (GRCm39)	Y46N	probably damaging	Het
F2	C	T	2: 91,456,075 (GRCm39)	G562D	probably damaging	Het
Fgf23	G	A	6: 127,057,128 (GRCm39)	G148D	probably damaging	Het
Fmnl3	G	C	15: 99,220,619 (GRCm39)		probably benign	Het
Fstl5	G	A	3: 76,614,786 (GRCm39)	G179R	probably damaging	Het
Garre1	A	T	7: 33,938,644 (GRCm39)	W246R	probably damaging	Het
Gart	T	A	16: 91,422,282 (GRCm39)	Q745L	probably benign	Het
Gmeb1	T	A	4: 131,959,419 (GRCm39)	M212L	probably benign	Het
Gpaa1	T	C	15: 76,218,981 (GRCm39)	Y548H	probably damaging	Het
Gpatch1	T	C	7: 34,986,667 (GRCm39)	E763G	probably damaging	Het
Grm8	T	A	6: 27,762,389 (GRCm39)	I279F	probably damaging	Het
Hcls1	T	A	16: 36,771,536 (GRCm39)	H147Q	probably damaging	Het
Hpcal1	A	C	12: 17,836,389 (GRCm39)	D73A	probably damaging	Het
Il22ra1	T	C	4: 135,478,317 (GRCm39)	S463P	probably benign	Het
Itgbl1	G	A	14: 124,078,098 (GRCm39)		probably null	Het
Izumo3	G	T	4: 92,035,437 (GRCm39)		probably benign	Het
Kcna5	A	T	6: 126,510,346 (GRCm39)	L594Q	probably damaging	Het
Kif13a	A	T	13: 46,918,079 (GRCm39)	D409E	probably benign	Het
Kif9	A	T	9: 110,314,106 (GRCm39)	I39F	probably damaging	Het
Klri2	C	T	6: 129,709,171 (GRCm39)	R227H	possibly damaging	Het
Lamc3	G	A	2: 31,798,628 (GRCm39)	G445S	probably damaging	Het
Lctl	A	G	9: 64,024,980 (GRCm39)		probably benign	Het
Lrp4	T	C	2: 91,325,327 (GRCm39)	L1384P	probably damaging	Het
Mcm9	G	A	10: 53,439,526 (GRCm39)	S549L	possibly damaging	Het
Ms4a15	G	A	19: 10,956,697 (GRCm39)		probably benign	Het
Mtor	T	C	4: 148,555,081 (GRCm39)	V901A	possibly damaging	Het
Nckap1l	A	T	15: 103,390,391 (GRCm39)	I721F	probably benign	Het
Nemp2	T	C	1: 52,684,588 (GRCm39)	V298A	probably benign	Het
Npr1	C	T	3: 90,363,244 (GRCm39)	V879M	probably damaging	Het
Odad4	A	G	11: 100,454,394 (GRCm39)	E393G	probably damaging	Het
Or2ad1	A	G	13: 21,326,336 (GRCm39)	V297A	possibly damaging	Het
Or51q1c	A	G	7: 103,652,709 (GRCm39)	T82A	probably benign	Het
Osgin1	A	T	8: 120,169,219 (GRCm39)	I39F	possibly damaging	Het
Phip	G	C	9: 82,809,244 (GRCm39)		probably null	Het
Pkdrej	G	T	15: 85,705,768 (GRCm39)	P56Q	possibly damaging	Het
Plcxd2	A	G	16: 45,800,889 (GRCm39)	Y112H	probably damaging	Het
Plekha1	C	T	7: 130,499,176 (GRCm39)	T155M	probably damaging	Het
Prkdc	T	C	16: 15,558,196 (GRCm39)		probably null	Het
Prss1	A	G	6: 41,439,495 (GRCm39)	H76R	probably damaging	Het
Psg23	T	C	7: 18,348,558 (GRCm39)	D83G	probably benign	Het
Ptprd	T	A	4: 76,055,140 (GRCm39)	Q196L	probably benign	Het
Ranbp3l	A	T	15: 9,063,067 (GRCm39)	H292L	probably damaging	Het
Ranbp6	T	C	19: 29,787,097 (GRCm39)	E1085G	probably benign	Het
Rccd1	A	G	7: 79,970,326 (GRCm39)	V97A	possibly damaging	Het
Rchy1	T	C	5: 92,105,458 (GRCm39)	S48G	probably benign	Het
Rnmt	G	A	18: 68,446,771 (GRCm39)	M265I	probably benign	Het
Robo3	A	T	9: 37,336,640 (GRCm39)	M376K	probably benign	Het
Rrp12	T	C	19: 41,862,289 (GRCm39)	D898G	probably benign	Het
Scg3	A	T	9: 75,570,462 (GRCm39)		probably benign	Het
Sec31b	A	T	19: 44,522,821 (GRCm39)	M57K	probably damaging	Het
Slc17a6	A	C	7: 51,315,892 (GRCm39)	I387L	probably benign	Het
Speer4a1	T	A	5: 26,240,982 (GRCm39)	Q170L	possibly damaging	Het
Srsf9	A	G	5: 115,470,260 (GRCm39)	D146G	possibly damaging	Het
Ss18	A	G	18: 14,788,200 (GRCm39)	M90T	probably damaging	Het
Syna	A	T	5: 134,588,314 (GRCm39)	F212I	possibly damaging	Het
Tex54	A	G	19: 8,718,221 (GRCm39)		probably benign	Het
Thsd1	A	G	8: 22,733,055 (GRCm39)	H34R	probably damaging	Het
Tmem143	T	C	7: 45,547,086 (GRCm39)	I84T	probably benign	Het
Trim50	T	C	5: 135,395,487 (GRCm39)	V281A	probably damaging	Het
Trp53i11	C	A	2: 93,029,696 (GRCm39)		probably benign	Het
Ttll4	C	T	1: 74,718,851 (GRCm39)	T234I	possibly damaging	Het
Ttyh1	A	T	7: 4,127,719 (GRCm39)	I136F	possibly damaging	Het
Ube2f	T	C	1: 91,189,976 (GRCm39)		probably benign	Het
Vcl	T	A	14: 21,037,083 (GRCm39)	L227*	probably null	Het
Vmn1r222	A	C	13: 23,416,974 (GRCm39)	C80G	probably damaging	Het
Vps13b	G	T	15: 35,926,365 (GRCm39)	A3889S	probably benign	Het
Vps8	T	C	16: 21,323,136 (GRCm39)		probably benign	Het
Zbtb44	A	G	9: 30,978,006 (GRCm39)	Y422C	probably damaging	Het
Zfp180	A	G	7: 23,805,158 (GRCm39)	S526G	possibly damaging	Het
Zfp518a	A	C	19: 40,904,310 (GRCm39)	E1413A	probably damaging	Het
Zfp629	T	A	7: 127,210,858 (GRCm39)	Y317F	probably damaging	Het
Zfp804b	T	C	5: 6,820,534 (GRCm39)	E843G	probably benign	Het

Other mutations in Npc1l1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00163:Npc1l1	APN	11	6,174,199 (GRCm39)	missense	probably damaging	1.00
IGL01348:Npc1l1	APN	11	6,177,974 (GRCm39)	missense	probably damaging	1.00
IGL01891:Npc1l1	APN	11	6,164,280 (GRCm39)	missense	probably damaging	1.00
IGL01897:Npc1l1	APN	11	6,177,879 (GRCm39)	missense	probably benign
IGL02098:Npc1l1	APN	11	6,164,581 (GRCm39)	missense	probably damaging	0.99
IGL02121:Npc1l1	APN	11	6,178,157 (GRCm39)	missense	probably benign
IGL02724:Npc1l1	APN	11	6,164,684 (GRCm39)	missense	possibly damaging	0.88
IGL02947:Npc1l1	APN	11	6,179,246 (GRCm39)	missense	probably benign	0.01
IGL03328:Npc1l1	APN	11	6,168,643 (GRCm39)	nonsense	probably null
R0322:Npc1l1	UTSW	11	6,179,042 (GRCm39)	missense	probably benign
R0352:Npc1l1	UTSW	11	6,173,076 (GRCm39)	missense	probably benign	0.00
R0492:Npc1l1	UTSW	11	6,173,040 (GRCm39)	missense	possibly damaging	0.82
R0918:Npc1l1	UTSW	11	6,168,239 (GRCm39)	missense	probably damaging	1.00
R1300:Npc1l1	UTSW	11	6,177,859 (GRCm39)	missense	probably damaging	1.00
R1455:Npc1l1	UTSW	11	6,178,174 (GRCm39)	missense	possibly damaging	0.66
R1588:Npc1l1	UTSW	11	6,167,785 (GRCm39)	missense	probably benign	0.01
R1803:Npc1l1	UTSW	11	6,178,846 (GRCm39)	missense	probably damaging	1.00
R1882:Npc1l1	UTSW	11	6,167,473 (GRCm39)	splice site	probably null
R1944:Npc1l1	UTSW	11	6,164,588 (GRCm39)	missense	possibly damaging	0.67
R1945:Npc1l1	UTSW	11	6,175,199 (GRCm39)	nonsense	probably null
R1945:Npc1l1	UTSW	11	6,164,588 (GRCm39)	missense	possibly damaging	0.67
R3155:Npc1l1	UTSW	11	6,171,840 (GRCm39)	missense	probably benign
R4343:Npc1l1	UTSW	11	6,167,773 (GRCm39)	missense	probably benign
R4504:Npc1l1	UTSW	11	6,178,741 (GRCm39)	missense	possibly damaging	0.61
R4610:Npc1l1	UTSW	11	6,178,215 (GRCm39)	missense	probably damaging	1.00
R4807:Npc1l1	UTSW	11	6,168,723 (GRCm39)	missense	probably damaging	1.00
R4829:Npc1l1	UTSW	11	6,164,010 (GRCm39)	critical splice donor site	probably null
R5135:Npc1l1	UTSW	11	6,174,245 (GRCm39)	missense	possibly damaging	0.94
R5290:Npc1l1	UTSW	11	6,172,221 (GRCm39)	missense	probably benign	0.00
R5369:Npc1l1	UTSW	11	6,167,705 (GRCm39)	critical splice donor site	probably null
R5388:Npc1l1	UTSW	11	6,164,733 (GRCm39)	missense	probably damaging	1.00
R5532:Npc1l1	UTSW	11	6,174,245 (GRCm39)	missense	probably damaging	0.98
R5540:Npc1l1	UTSW	11	6,164,546 (GRCm39)	missense	probably damaging	1.00
R5754:Npc1l1	UTSW	11	6,177,839 (GRCm39)	missense	probably damaging	1.00
R5760:Npc1l1	UTSW	11	6,179,031 (GRCm39)	missense	probably benign	0.02
R6057:Npc1l1	UTSW	11	6,167,806 (GRCm39)	missense	possibly damaging	0.66
R6388:Npc1l1	UTSW	11	6,174,145 (GRCm39)	missense	probably damaging	1.00
R6644:Npc1l1	UTSW	11	6,164,014 (GRCm39)	missense	probably damaging	0.98
R6644:Npc1l1	UTSW	11	6,164,013 (GRCm39)	missense	probably damaging	1.00
R6756:Npc1l1	UTSW	11	6,165,153 (GRCm39)	missense	probably damaging	1.00
R6790:Npc1l1	UTSW	11	6,164,260 (GRCm39)	splice site	probably null
R7006:Npc1l1	UTSW	11	6,167,731 (GRCm39)	missense	probably benign
R7062:Npc1l1	UTSW	11	6,167,807 (GRCm39)	missense	probably benign
R7273:Npc1l1	UTSW	11	6,168,320 (GRCm39)	missense	probably damaging	1.00
R7383:Npc1l1	UTSW	11	6,167,777 (GRCm39)	missense	probably benign	0.30
R8003:Npc1l1	UTSW	11	6,165,129 (GRCm39)	missense	probably benign	0.01
R8081:Npc1l1	UTSW	11	6,167,768 (GRCm39)	missense	probably benign	0.01
R8272:Npc1l1	UTSW	11	6,179,327 (GRCm39)	nonsense	probably null
R8549:Npc1l1	UTSW	11	6,168,675 (GRCm39)	missense	probably damaging	1.00
R8849:Npc1l1	UTSW	11	6,179,038 (GRCm39)	missense	probably damaging	0.97
R8887:Npc1l1	UTSW	11	6,175,665 (GRCm39)	missense	probably damaging	1.00
R8907:Npc1l1	UTSW	11	6,178,157 (GRCm39)	missense	probably benign	0.28
R9102:Npc1l1	UTSW	11	6,164,684 (GRCm39)	missense	possibly damaging	0.88
R9289:Npc1l1	UTSW	11	6,168,355 (GRCm39)	nonsense	probably null
R9626:Npc1l1	UTSW	11	6,177,854 (GRCm39)	missense	probably benign	0.05
R9785:Npc1l1	UTSW	11	6,180,090 (GRCm39)	missense	unknown
X0022:Npc1l1	UTSW	11	6,178,058 (GRCm39)	missense	probably damaging	1.00
Z1177:Npc1l1	UTSW	11	6,175,209 (GRCm39)	missense	possibly damaging	0.92
Z1177:Npc1l1	UTSW	11	6,168,681 (GRCm39)	missense	probably damaging	0.99
Z1177:Npc1l1	UTSW	11	6,164,343 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GAAATGGTCCTTCCAGTCCACCAG -3'
(R):5'- CTCGTAAGCGCAGATTCTCACCTC -3'

Sequencing Primer
(F):5'- TTGACACAGCAGTCAGTGAG -3'
(R):5'- TCTTCGAGAGCTGGGGAAC -3'

Posted On

2013-04-12