Mutagenetix > Incidental Mutation

Incidental Mutation 'R8831:Npc1'

673872

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

068659-MU

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.616) question?

Stock #

R8831 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

12322749-12369457 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 12333877 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Methionine to Leucine at position 735 (M735L)

Ref Sequence

ENSEMBL: ENSMUSP00000025279 (fasta)

Gene Model

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

AlphaFold

O35604

Predicted Effect

probably benign
Transcript: ENSMUST00000025279
AA Change: M735L

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

SMART Domains

Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: M735L

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

Meta Mutation Damage Score

0.1097

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.9%

Validation Efficiency

99% (81/82)

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: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
A230072I06Rik	A	T	8: 12,329,688 (GRCm39)	I48L	unknown	Het
Abcc3	A	C	11: 94,241,787 (GRCm39)	C1415G	probably damaging	Het
Abcf3	C	T	16: 20,369,214 (GRCm39)	R205C	probably damaging	Het
Abcg5	G	T	17: 84,976,423 (GRCm39)	H471Q	probably damaging	Het
Actl6b	G	A	5: 137,565,305 (GRCm39)	R363Q	probably damaging	Het
Adcy1	T	A	11: 7,111,362 (GRCm39)	D884E	probably benign	Het
Aldh3a1	A	G	11: 61,107,142 (GRCm39)	Y282C	probably damaging	Het
Amdhd2	A	G	17: 24,376,712 (GRCm39)		probably null	Het
Arfgef3	A	G	10: 18,528,491 (GRCm39)	S299P	possibly damaging	Het
Asic2	A	T	11: 81,858,726 (GRCm39)	N95K	probably damaging	Het
Atp2c2	A	G	8: 120,476,033 (GRCm39)		probably null	Het
Atrn	T	C	2: 130,748,521 (GRCm39)	L14P	probably benign	Het
C8b	A	G	4: 104,647,874 (GRCm39)	Y355C	probably damaging	Het
Carm1	A	G	9: 21,491,663 (GRCm39)	E244G	probably damaging	Het
Cd300c2	A	T	11: 114,891,844 (GRCm39)	C39*	probably null	Het
Cish	T	A	9: 107,177,671 (GRCm39)	F116I	probably damaging	Het
Clstn1	G	A	4: 149,730,780 (GRCm39)	R837Q	probably benign	Het
Cox10	A	G	11: 63,855,306 (GRCm39)	F325S	probably damaging	Het
Cplane1	T	C	15: 8,211,620 (GRCm39)	I320T	probably benign	Het
Ctps1	A	T	4: 120,424,507 (GRCm39)	S36T	possibly damaging	Het
Dchs2	T	C	3: 83,192,670 (GRCm39)	L1705P	probably benign	Het
Defb25	C	A	2: 152,464,899 (GRCm39)	V17L	probably benign	Het
Dhx16	A	G	17: 36,199,000 (GRCm39)	D782G	probably damaging	Het
Dhx30	A	G	9: 109,917,319 (GRCm39)	S399P	probably benign	Het
Dhx58	T	A	11: 100,594,806 (GRCm39)	K30M	probably damaging	Het
Drc7	G	A	8: 95,788,845 (GRCm39)	R301Q	probably damaging	Het
Dsg1a	T	C	18: 20,453,365 (GRCm39)	V21A	probably damaging	Het
Ercc6	T	A	14: 32,282,784 (GRCm39)		probably null	Het
Fam193a	A	G	5: 34,616,374 (GRCm39)	T850A	probably benign	Het
Fgf10	A	G	13: 118,925,671 (GRCm39)	D150G	probably damaging	Het
Flii	A	T	11: 60,616,074 (GRCm39)	N28K	probably benign	Het
Gfi1	G	A	5: 107,868,138 (GRCm39)	R377C	probably damaging	Het
Gfra2	A	T	14: 71,204,503 (GRCm39)	N324I	probably benign	Het
Gm10308	A	G	17: 91,396,431 (GRCm39)	R118G	unknown	Het
Gm10801	T	A	2: 98,494,334 (GRCm39)	V137E	probably damaging	Het
Hmmr	G	A	11: 40,612,499 (GRCm39)	S206F	probably damaging	Het
Hsd3b9	A	T	3: 98,354,047 (GRCm39)	W151R	probably benign	Het
Ift80	G	A	3: 68,869,583 (GRCm39)	A236V	probably damaging	Het
Il1rn	A	T	2: 24,239,505 (GRCm39)	T134S	possibly damaging	Het
Il6st	G	T	13: 112,640,914 (GRCm39)	D897Y	probably damaging	Het
Imp4	T	C	1: 34,483,445 (GRCm39)	M257T	probably benign	Het
Impdh2	T	C	9: 108,441,957 (GRCm39)	L377S	probably damaging	Het
Kdm1b	C	A	13: 47,217,617 (GRCm39)	L359I	possibly damaging	Het
Kidins220	A	T	12: 25,086,454 (GRCm39)	I963L	possibly damaging	Het
Mdm4	T	C	1: 132,931,601 (GRCm39)	R148G	probably benign	Het
Myl10	G	C	5: 136,726,825 (GRCm39)	V70L	probably benign	Het
Ncor1	A	T	11: 62,260,234 (GRCm39)	D505E	probably benign	Het
Necab3	A	T	2: 154,396,607 (GRCm39)	L107Q	probably damaging	Het
Nkx2-4	G	A	2: 146,927,114 (GRCm39)	P51L	probably benign	Het
Nol11	T	C	11: 107,067,662 (GRCm39)	T388A	probably benign	Het
Nr1h3	C	A	2: 91,021,091 (GRCm39)	R232L	probably benign	Het
Nrcam	T	A	12: 44,591,680 (GRCm39)		probably null	Het
Or1j13	G	A	2: 36,369,794 (GRCm39)	T116I	possibly damaging	Het
Or52s1b	T	A	7: 102,822,203 (GRCm39)	I214L	probably benign	Het
Pabpn1	T	C	14: 55,131,914 (GRCm39)	V101A	probably damaging	Het
Pcare	A	T	17: 72,059,305 (GRCm39)	V124E	probably benign	Het
Pcbp2	A	G	15: 102,394,453 (GRCm39)	D217G	probably benign	Het
Pcdhb12	A	G	18: 37,570,386 (GRCm39)	M511V	probably benign	Het
Phf3	T	A	1: 30,860,347 (GRCm39)	K828*	probably null	Het
Plcg1	G	C	2: 160,589,732 (GRCm39)	K85N	probably benign	Het
Prag1	A	T	8: 36,613,891 (GRCm39)	T1148S	probably benign	Het
Prmt3	A	G	7: 49,478,729 (GRCm39)	E430G	probably null	Het
Prx	G	T	7: 27,217,538 (GRCm39)	V819F	probably damaging	Het
Ptpn18	A	T	1: 34,511,271 (GRCm39)	R338W	probably null	Het
Rab6a	T	C	7: 100,283,931 (GRCm39)	Y128H	probably benign	Het
Rgs2	T	C	1: 143,877,497 (GRCm39)	Y186C	probably damaging	Het
Rhbdl1	C	T	17: 26,053,857 (GRCm39)	V342M	probably damaging	Het
Rpn1	A	G	6: 88,061,775 (GRCm39)	Q88R	probably benign	Het
Slc19a2	C	T	1: 164,084,443 (GRCm39)	T111M	probably damaging	Het
Slc35e4	G	A	11: 3,863,087 (GRCm39)	P34L	possibly damaging	Het
Slc7a6os	A	T	8: 106,937,189 (GRCm39)	D90E	probably benign	Het
Ssh3	A	G	19: 4,319,053 (GRCm39)	V19A	possibly damaging	Het
Susd1	C	T	4: 59,379,594 (GRCm39)		probably benign	Het
Tcf19	A	T	17: 35,825,794 (GRCm39)	M121K	possibly damaging	Het
Tcp11	G	A	17: 28,299,193 (GRCm39)	R21C	probably damaging	Het
Tcp11l2	A	G	10: 84,449,522 (GRCm39)	I496V	probably damaging	Het
Tenm3	C	T	8: 48,729,417 (GRCm39)	A1530T		Het
Tmem127	T	A	2: 127,098,979 (GRCm39)	V171D	probably damaging	Het
Tyrp1	G	A	4: 80,753,399 (GRCm39)	C30Y	probably damaging	Het
Usp48	A	T	4: 137,341,080 (GRCm39)	D360V	probably damaging	Het
Vamp4	T	A	1: 162,401,952 (GRCm39)	D11E	possibly damaging	Het
Vmn1r14	T	C	6: 57,210,505 (GRCm39)	F28L	probably benign	Het
Vmn2r69	G	T	7: 85,059,018 (GRCm39)	C514*	probably null	Het
Vmn2r84	G	A	10: 130,226,968 (GRCm39)	A290V	probably benign	Het
Zfp1007	A	T	5: 109,824,174 (GRCm39)	S425R	probably benign	Het
Zhx3	T	A	2: 160,622,691 (GRCm39)	Y492F	probably benign	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
R2117:Npc1	UTSW	18	12,329,613 (GRCm39)	missense	probably damaging	1.00
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
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'- AGCCCAGCATCAGTACTGTG -3'
(R):5'- AACGGCATTAGTCAGCTGC -3'

Sequencing Primer
(F):5'- AGCATCAGTACTGTGCTGGGAC -3'
(R):5'- GCATTAGTCAGCTGCTGCAG -3'

Posted On

2021-07-15