Mutagenetix > Incidental Mutation

Incidental Mutation 'R6756:Npc1l1'

531064

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

044872-MU

Accession Numbers

Essential gene?

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

Stock #

R6756 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

6161013-6180143 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 6165153 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Cysteine at position 1053 (Y1053C)

Ref Sequence

ENSEMBL: ENSMUSP00000004505 (fasta)

Gene Model

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

AlphaFold

no structure available at present

Predicted Effect

probably damaging
Transcript: ENSMUST00000004505
AA Change: Y1053C

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: Y1053C

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

Coding Region Coverage

1x: 99.9%
3x: 99.6%
10x: 98.2%
20x: 95.1%

Validation Efficiency

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: 28 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abca12	C	T	1: 71,298,512 (GRCm39)		probably null	Het
Adam7	T	C	14: 68,762,728 (GRCm39)	T166A	probably benign	Het
Ahnak	G	A	19: 8,984,925 (GRCm39)	V2070M	possibly damaging	Het
Atp6v1a	T	A	16: 43,909,421 (GRCm39)	T537S	probably benign	Het
Atp8b3	C	T	10: 80,361,895 (GRCm39)	E719K	possibly damaging	Het
Clba1	T	C	12: 112,775,820 (GRCm39)	L192P	probably damaging	Het
Dpy19l1	T	C	9: 24,385,080 (GRCm39)	T250A	probably damaging	Het
Fra10ac1	A	C	19: 38,204,313 (GRCm39)	Y88D	probably damaging	Het
Gm21738	C	T	14: 19,418,824 (GRCm38)	V35I	possibly damaging	Het
H2-M9	G	T	17: 36,953,227 (GRCm39)	H27N	probably damaging	Het
Hivep2	T	C	10: 14,008,303 (GRCm39)	C1634R	probably damaging	Het
Meiob	A	T	17: 25,058,506 (GRCm39)	T470S	possibly damaging	Het
Ms4a7	T	C	19: 11,301,889 (GRCm39)	H35R	possibly damaging	Het
Myl10	G	C	5: 136,726,825 (GRCm39)	V70L	probably benign	Het
Nf1	T	A	11: 79,335,413 (GRCm39)		probably null	Het
Or4p21	T	C	2: 88,277,078 (GRCm39)	D68G	possibly damaging	Het
Or51a25	T	C	7: 102,373,295 (GRCm39)	N134S	probably benign	Het
Pcdh10	T	C	3: 45,334,541 (GRCm39)	V285A	possibly damaging	Het
Phldb2	A	T	16: 45,628,683 (GRCm39)	C550S	probably benign	Het
Phldb3	T	C	7: 24,326,756 (GRCm39)	Y595H	probably damaging	Het
Plekha8	C	T	6: 54,601,125 (GRCm39)	Q288*	probably null	Het
Ppp1r36	G	A	12: 76,474,696 (GRCm39)	A64T	probably benign	Het
Ptprd	T	C	4: 75,873,536 (GRCm39)	T1320A	probably damaging	Het
R3hdm1	GAA	GAAA	1: 128,090,548 (GRCm39)		probably null	Het
Recql4	T	C	15: 76,589,059 (GRCm39)	D943G	probably benign	Het
Slc24a2	A	G	4: 87,094,529 (GRCm39)	I330T	probably benign	Het
Srcin1	T	C	11: 97,425,836 (GRCm39)	D433G	probably damaging	Het
Upb1	A	G	10: 75,264,135 (GRCm39)	T194A	possibly damaging	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
R0137:Npc1l1	UTSW	11	6,178,148 (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
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'- CCCAACATCTCTTGTGTGGC -3'
(R):5'- TCTCAGTGGCAGAAGTAGAGTTTG -3'

Sequencing Primer
(F):5'- AACATCTCTTGTGTGGCTGTTTC -3'
(R):5'- GACTGCCTTTAAGTCCAGTTACAGG -3'

Posted On

2018-08-01