Mutagenetix > Incidental Mutation

Incidental Mutation 'R9723:Npc1'

730962

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

Accession Numbers

Essential gene?

Possibly essential (E-score: 0.616) question?

Stock #

R9723 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

12322749-12369457 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 12343649 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Threonine at position 448 (I448T)

Ref Sequence

ENSEMBL: ENSMUSP00000025279 (fasta)

Gene Model

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

AlphaFold

O35604

Predicted Effect

probably benign
Transcript: ENSMUST00000025279
AA Change: I448T

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000025279
Gene: ENSMUSG00000024413
AA Change: I448T

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.1%

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: 83 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abcb6	G	A	1: 75,156,366 (GRCm39)	R133W	probably benign	Het
Abcc3	T	A	11: 94,250,725 (GRCm39)	T877S	probably benign	Het
Alb	A	T	5: 90,611,962 (GRCm39)	K130N	probably damaging	Het
Alkbh8	G	A	9: 3,385,283 (GRCm39)	S560N	probably benign	Het
Angel2	T	G	1: 190,671,342 (GRCm39)	L234R	probably damaging	Het
Catip	C	T	1: 74,403,745 (GRCm39)	T154I	probably benign	Het
Ccdc163	C	T	4: 116,569,595 (GRCm39)	Q102*	probably null	Het
Cep250	A	G	2: 155,823,337 (GRCm39)	E997G	probably benign	Het
Ces2f	T	C	8: 105,677,463 (GRCm39)	I183T	possibly damaging	Het
Commd8	A	G	5: 72,318,309 (GRCm39)	V158A	possibly damaging	Het
Cyp2b9	C	T	7: 25,909,596 (GRCm39)	Q455*	probably null	Het
D5Ertd579e	G	T	5: 36,772,284 (GRCm39)	H704N	probably damaging	Het
Dnah1	T	C	14: 30,987,946 (GRCm39)	T3491A	probably damaging	Het
Dnai1	T	G	4: 41,603,302 (GRCm39)	F195C	possibly damaging	Het
Dock7	A	G	4: 98,908,270 (GRCm39)	V620A		Het
Dock7	A	T	4: 98,960,660 (GRCm39)	D289E		Het
Dpys	T	A	15: 39,691,509 (GRCm39)	E271V	probably damaging	Het
Elovl3	T	C	19: 46,123,155 (GRCm39)	Y244H	probably damaging	Het
Enam	G	A	5: 88,652,241 (GRCm39)	G1250E	probably damaging	Het
Espl1	C	T	15: 102,229,170 (GRCm39)	T1774M	probably benign	Het
Fasl	T	C	1: 161,615,535 (GRCm39)	K107R	probably benign	Het
Fbn1	A	T	2: 125,202,119 (GRCm39)	C1251*	probably null	Het
Fn1	G	T	1: 71,663,369 (GRCm39)	Q1040K	possibly damaging	Het
Frem3	C	T	8: 81,341,352 (GRCm39)	S1215L	probably benign	Het
G3bp2	A	T	5: 92,214,388 (GRCm39)	D135E	possibly damaging	Het
Gabpb1	C	T	2: 126,488,648 (GRCm39)	V240I	probably benign	Het
Galnt12	C	G	4: 47,119,541 (GRCm39)	Y452*	probably null	Het
Ggta1	G	T	2: 35,303,418 (GRCm39)	D91E	probably benign	Het
Gm12258	C	T	11: 58,750,448 (GRCm39)	P541L	unknown	Het
Gm12789	T	A	4: 101,846,083 (GRCm39)	W115R	possibly damaging	Het
Gm8126	T	C	14: 43,119,141 (GRCm39)		probably null	Het
Gpr179	A	T	11: 97,225,546 (GRCm39)	L2203H	possibly damaging	Het
H1f6	A	G	13: 23,879,906 (GRCm39)	K20E	probably damaging	Het
Hapln3	A	T	7: 78,771,736 (GRCm39)	V51E	possibly damaging	Het
Ifit1	A	G	19: 34,626,257 (GRCm39)	*464W	probably null	Het
Il1r1	A	C	1: 40,332,721 (GRCm39)	I137L	probably benign	Het
Il1rap	T	A	16: 26,442,907 (GRCm39)	M1K	probably null	Het
Lgi2	A	G	5: 52,695,843 (GRCm39)	L372P	probably damaging	Het
Lrrc46	A	G	11: 96,925,773 (GRCm39)	S230P	possibly damaging	Het
Ltbr	G	A	6: 125,284,348 (GRCm39)	R365W	probably damaging	Het
Mapk8ip3	C	A	17: 25,132,585 (GRCm39)	W339L	possibly damaging	Het
Msln	A	T	17: 25,969,008 (GRCm39)	M459K	possibly damaging	Het
Msr1	A	G	8: 40,042,357 (GRCm39)	V406A	possibly damaging	Het
Ndst2	G	T	14: 20,775,512 (GRCm39)	D659E	probably benign	Het
Npat	T	A	9: 53,473,746 (GRCm39)	S513T	probably benign	Het
Npat	T	G	9: 53,481,861 (GRCm39)	L1190V	probably damaging	Het
Omd	T	C	13: 49,743,838 (GRCm39)	F296S	probably damaging	Het
Oprm1	A	G	10: 6,788,514 (GRCm39)	N423S	possibly damaging	Het
Oxtr	G	A	6: 112,466,304 (GRCm39)	T152I	probably benign	Het
Pak2	A	T	16: 31,852,650 (GRCm39)	V297E	probably damaging	Het
Pcnx4	T	C	12: 72,603,039 (GRCm39)	Y434H	probably damaging	Het
Pet100	G	A	8: 3,672,374 (GRCm39)	M20I	probably damaging	Het
Pfpl	G	C	19: 12,406,297 (GRCm39)	E183Q	probably damaging	Het
Plekhn1	A	G	4: 156,306,875 (GRCm39)	S505P	probably benign	Het
Plin5	G	A	17: 56,423,290 (GRCm39)	A90V	probably damaging	Het
Poc5	A	G	13: 96,551,026 (GRCm39)	T526A	probably benign	Het
Potefam1	T	C	2: 111,058,700 (GRCm39)	H84R	probably damaging	Het
Pramel7	C	T	2: 87,320,019 (GRCm39)	V425I	possibly damaging	Het
Rad51d	A	T	11: 82,781,162 (GRCm39)		probably null	Het
Rbp3	T	C	14: 33,677,474 (GRCm39)	M474T	possibly damaging	Het
Rcan3	A	G	4: 135,152,680 (GRCm39)	S14P	probably benign	Het
Rps6ka4	A	T	19: 6,816,663 (GRCm39)	V140E	probably damaging	Het
Rsbn1l	G	A	5: 21,101,464 (GRCm39)	S692L	possibly damaging	Het
Sgk1	A	T	10: 21,872,239 (GRCm39)	I272F	probably damaging	Het
Skor1	A	G	9: 63,053,714 (GRCm39)	V85A	probably damaging	Het
Slc12a1	A	T	2: 125,059,827 (GRCm39)	D909V	probably damaging	Het
Slc25a18	C	A	6: 120,770,489 (GRCm39)	A283E	probably benign	Het
Slc41a1	T	C	1: 131,772,103 (GRCm39)	L411P	possibly damaging	Het
Spata13	T	C	14: 60,928,498 (GRCm39)	S19P	probably damaging	Het
Stab1	T	A	14: 30,885,848 (GRCm39)	H42L	probably benign	Het
Stag3	T	A	5: 138,298,103 (GRCm39)	D698E	probably benign	Het
Syngap1	G	A	17: 27,189,510 (GRCm39)	R1305H	possibly damaging	Het
Tek	T	G	4: 94,692,539 (GRCm39)	W216G	possibly damaging	Het
Trappc9	A	G	15: 72,461,963 (GRCm39)	Y1101H	possibly damaging	Het
Ttn	A	G	2: 76,601,929 (GRCm39)	Y10251H	probably damaging	Het
Uhrf1	A	G	17: 56,625,061 (GRCm39)	K535E	probably damaging	Het
Usp14	G	T	18: 10,009,993 (GRCm39)	Q185K	probably damaging	Het
Usp32	A	T	11: 84,935,536 (GRCm39)	Y413*	probably null	Het
Uvssa	G	A	5: 33,547,382 (GRCm39)		probably null	Het
Vmn1r177	A	T	7: 23,565,774 (GRCm39)	L34Q	probably damaging	Het
Wdr41	T	C	13: 95,151,671 (GRCm39)	L277P	probably damaging	Het
Zc2hc1b	T	A	10: 13,044,497 (GRCm39)	L55F	probably damaging	Het
Zfp345	A	C	2: 150,314,189 (GRCm39)	Y449*	probably null	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
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
X0012:Npc1	UTSW	18	12,326,368 (GRCm39)	splice site	probably null

Predicted Primers

PCR Primer
(F):5'- AGCGTAGATATAGAAGTCGTCGC -3'
(R):5'- TGGTCATGATGTCTCCGTCC -3'

Sequencing Primer
(F):5'- ATAGAAGTCGTCGCCTACTTG -3'
(R):5'- ATGATGTCTCCGTCCCAGAC -3'

Posted On

2022-10-06