Mutagenetix > Incidental Mutation

Incidental Mutation 'R6057:Npc1l1'

482990

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

Accession Numbers

Essential gene?

Probably non essential (E-score: 0.098) question?

Stock #

R6057 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

6161013-6180143 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 6167806 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Lysine at position 995 (M995K)

Ref Sequence

ENSEMBL: ENSMUSP00000004505 (fasta)

Gene Model

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

AlphaFold

no structure available at present

Predicted Effect

possibly damaging
Transcript: ENSMUST00000004505
AA Change: M995K

PolyPhen 2 Score 0.656 (Sensitivity: 0.87; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000004505
Gene: ENSMUSG00000020447
AA Change: M995K

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: 97.9%
20x: 93.6%

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: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
5730596B20Rik	A	G	6: 52,156,500 (GRCm39)		probably benign	Het
Acan	A	G	7: 78,749,530 (GRCm39)	S11G	probably null	Het
Ankrd13d	A	C	19: 4,332,256 (GRCm39)	V56G	probably damaging	Het
Arl15	A	G	13: 114,104,151 (GRCm39)	Y76C	probably damaging	Het
Aspg	G	A	12: 112,087,432 (GRCm39)	C296Y	probably damaging	Het
Astl	T	A	2: 127,187,889 (GRCm39)	D101E	probably benign	Het
Bmpr2	A	G	1: 59,881,977 (GRCm39)	N202S	probably benign	Het
Borcs7	T	C	19: 46,690,003 (GRCm39)	*106Q	probably null	Het
Brip1	A	G	11: 85,955,865 (GRCm39)	S883P	possibly damaging	Het
Cacng2	A	T	15: 78,002,991 (GRCm39)	L34Q	probably damaging	Het
Catip	A	C	1: 74,402,077 (GRCm39)	D84A	probably damaging	Het
Ccdc162	A	G	10: 41,510,037 (GRCm39)	L856S	possibly damaging	Het
Ccdc38	A	G	10: 93,417,608 (GRCm39)	K500E	probably damaging	Het
Ccser2	T	C	14: 36,663,122 (GRCm39)	K21E	probably damaging	Het
Cd93	A	T	2: 148,283,439 (GRCm39)	Y636N	probably damaging	Het
Cep128	A	T	12: 91,262,998 (GRCm39)	N300K	possibly damaging	Het
Cfap44	A	G	16: 44,269,460 (GRCm39)	T1155A	probably benign	Het
Clec16a	T	C	16: 10,447,951 (GRCm39)	L550P	probably damaging	Het
Csmd3	T	C	15: 47,618,787 (GRCm39)	Y1867C	probably damaging	Het
Cul3	A	T	1: 80,249,249 (GRCm39)	I674N	probably damaging	Het
Cybb	C	G	X: 9,316,989 (GRCm39)	D246H	probably benign	Het
Cyp2d34	T	C	15: 82,500,552 (GRCm39)	H429R	probably benign	Het
Dab2ip	T	A	2: 35,582,267 (GRCm39)	C4*	probably null	Het
Dcaf1	A	G	9: 106,731,446 (GRCm39)	E641G	probably damaging	Het
Dda1	T	A	8: 71,927,276 (GRCm39)		probably benign	Het
Dmgdh	C	T	13: 93,888,960 (GRCm39)	T866I	probably benign	Het
Ect2l	T	C	10: 18,037,250 (GRCm39)	T383A	probably benign	Het
Ets2	A	G	16: 95,515,416 (GRCm39)	N181D	probably benign	Het
Ezh2	A	G	6: 47,529,357 (GRCm39)	F222L	probably damaging	Het
Frem3	T	C	8: 81,342,216 (GRCm39)	L1503P	probably damaging	Het
Fsip2	C	A	2: 82,809,777 (GRCm39)	A2032E	probably damaging	Het
Gm1818	C	T	12: 48,602,346 (GRCm39)		noncoding transcript	Het
Gm9493	A	G	19: 23,597,106 (GRCm39)	S1G	probably damaging	Het
Grin2b	A	G	6: 135,710,942 (GRCm39)	I868T	possibly damaging	Het
Ift22	A	T	5: 136,939,987 (GRCm39)	T17S	possibly damaging	Het
Il4ra	T	C	7: 125,170,735 (GRCm39)	W216R	probably damaging	Het
Kcnj6	A	T	16: 94,633,236 (GRCm39)	W274R	probably damaging	Het
Kctd19	G	A	8: 106,123,082 (GRCm39)	H111Y	probably damaging	Het
Kremen2	A	G	17: 23,961,679 (GRCm39)	V276A	probably benign	Het
Lig1	C	A	7: 13,022,598 (GRCm39)	Q143K	probably damaging	Het
Lrp1	A	T	10: 127,403,359 (GRCm39)	D2071E	probably damaging	Het
Macf1	C	T	4: 123,404,536 (GRCm39)	M475I	probably damaging	Het
Mbtd1	G	A	11: 93,820,485 (GRCm39)	A427T	probably damaging	Het
Myof	A	G	19: 37,915,429 (GRCm39)		probably null	Het
Nbeal2	T	C	9: 110,470,945 (GRCm39)	D308G	possibly damaging	Het
Ncdn	T	C	4: 126,638,824 (GRCm39)	Q665R	probably benign	Het
Nkd1	T	C	8: 89,316,442 (GRCm39)		probably null	Het
Nktr	G	A	9: 121,577,455 (GRCm39)		probably benign	Het
Or10ag59	C	A	2: 87,406,363 (GRCm39)	R312S	probably benign	Het
Or11g7	A	T	14: 50,691,201 (GRCm39)	R231*	probably null	Het
Or14n1-ps1	T	A	7: 86,092,397 (GRCm39)	C69*	probably null	Het
Padi4	T	C	4: 140,487,351 (GRCm39)	T184A	probably damaging	Het
Pgm2l1	C	T	7: 99,915,881 (GRCm39)	P409S	probably benign	Het
Pgpep1	G	A	8: 71,105,101 (GRCm39)	T53M	probably damaging	Het
Pgr	T	C	9: 8,902,006 (GRCm39)	L513P	probably damaging	Het
Pikfyve	T	A	1: 65,311,730 (GRCm39)	I1989N	probably damaging	Het
Prrc2a	T	C	17: 35,371,716 (GRCm39)	T1806A	probably benign	Het
Psd	T	C	19: 46,311,753 (GRCm39)	E309G	possibly damaging	Het
Qtrt1	C	T	9: 21,323,299 (GRCm39)	T50I	probably damaging	Het
Rims2	A	C	15: 39,538,416 (GRCm39)	T1320P	probably damaging	Het
Scn11a	T	G	9: 119,594,514 (GRCm39)	N1293T	probably damaging	Het
Scn8a	T	C	15: 100,872,548 (GRCm39)	F529S	possibly damaging	Het
Sec14l4	A	T	11: 3,985,142 (GRCm39)	D25V	possibly damaging	Het
Sema3a	C	T	5: 13,615,832 (GRCm39)	R419C	probably damaging	Het
Slc12a1	T	C	2: 125,032,133 (GRCm39)	Y595H	probably damaging	Het
Slc25a28	A	T	19: 43,655,364 (GRCm39)	H170Q	possibly damaging	Het
Slc26a1	T	A	5: 108,821,631 (GRCm39)	Q86L	probably damaging	Het
Slc48a1	T	A	15: 97,687,798 (GRCm39)	W51R	probably damaging	Het
Sptlc3	T	A	2: 139,423,533 (GRCm39)	V309D	probably damaging	Het
Srcap	G	A	7: 127,140,528 (GRCm39)	S1375N	probably damaging	Het
Tanc1	C	A	2: 59,647,837 (GRCm39)	H986Q	possibly damaging	Het
Tbc1d4	A	G	14: 101,727,353 (GRCm39)	V486A	probably damaging	Het
Tceanc2	T	C	4: 107,004,776 (GRCm39)	D124G	probably damaging	Het
Tdrd9	A	G	12: 111,979,720 (GRCm39)	M402V	possibly damaging	Het
Tmem132d	T	C	5: 127,861,934 (GRCm39)	D729G	probably damaging	Het
Tmem62	T	A	2: 120,807,943 (GRCm39)	I55N	probably damaging	Het
Tnfrsf21	A	T	17: 43,350,606 (GRCm39)	N257Y	possibly damaging	Het
Trappc3	T	C	4: 126,167,834 (GRCm39)	L131P	probably damaging	Het
Vmn2r25	A	T	6: 123,799,900 (GRCm39)	M814K	possibly damaging	Het
Vmn2r87	T	C	10: 130,308,226 (GRCm39)	I671V	probably benign	Het
Vwa8	A	T	14: 79,320,313 (GRCm39)	D1108V	probably benign	Het
Xrcc4	C	G	13: 90,139,198 (GRCm39)	A241P	possibly damaging	Het
Xylt1	T	A	7: 117,191,135 (GRCm39)	D310E	probably benign	Het
Zfp27	T	G	7: 29,594,444 (GRCm39)	H507P	possibly damaging	Het
Zfp341	C	T	2: 154,466,954 (GRCm39)	P108S	probably benign	Het
Zfp641	T	C	15: 98,190,816 (GRCm39)	N76S	probably benign	Het
Zfp936	T	C	7: 42,839,787 (GRCm39)	V418A	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
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
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'- AACGAGACCTTGTCCTGTCAG -3'
(R):5'- GGAGATCCCATTTCTTGACCC -3'

Posted On

2017-07-14