Mutagenetix > Incidental Mutation

Incidental Mutation 'R1524:Ncstn'

167689

Institutional Source

Beutler Lab

Gene Symbol

Ncstn

Ensembl Gene

ENSMUSG00000003458

Gene Name

nicastrin

Synonyms

Nct, nicastrin, D1Dau13e, 9430068N19Rik

MMRRC Submission

039565-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1524 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

172066013-172082795 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 172072149 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Arginine to Leucine at position 322 (R322L)

Ref Sequence

ENSEMBL: ENSMUSP00000003550 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000003550] [ENSMUST00000140643] [ENSMUST00000146137]

AlphaFold

P57716

Predicted Effect

possibly damaging
Transcript: ENSMUST00000003550
AA Change: R322L

PolyPhen 2 Score 0.580 (Sensitivity: 0.88; Specificity: 0.91)

SMART Domains

Protein: ENSMUSP00000003550
Gene: ENSMUSG00000003458
AA Change: R322L

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC
Pfam:Peptidase_M28	254	468	2.9e-7	PFAM
Pfam:Nicastrin	273	498	1.6e-94	PFAM
transmembrane domain	669	691	N/A	INTRINSIC

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000122986

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135928

Predicted Effect

probably benign
Transcript: ENSMUST00000140643

SMART Domains

Protein: ENSMUSP00000119128
Gene: ENSMUSG00000003458

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000146137

SMART Domains

Protein: ENSMUSP00000120663
Gene: ENSMUSG00000003458

Domain	Start	End	E-Value	Type
signal peptide	1	32	N/A	INTRINSIC

Meta Mutation Damage Score

0.4147

Coding Region Coverage

1x: 99.3%
3x: 98.7%
10x: 97.3%
20x: 95.5%

Validation Efficiency

97% (68/70)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a type I transmembrane glycoprotein that is an integral component of the multimeric gamma-secretase complex. The encoded protein cleaves integral membrane proteins, including Notch receptors and beta-amyloid precursor protein, and may be a stabilizing cofactor required for gamma-secretase complex assembly. The cleavage of beta-amyloid precursor protein yields amyloid beta peptide, the main component of the neuritic plaque and the hallmark lesion in the brains of patients with Alzheimer's disease; however, the nature of the encoded protein's role in Alzheimer's disease is not known for certain. Mutations in this gene are associated with familial acne inversa. A pseudogene of this gene is present on chromosome 21. Alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Feb 2014]
PHENOTYPE: Homozygous mutant embryos die exhibiting morphological defects of the somites, yolk sac vasculature, neural tube, and pericardial sacs. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 67 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2310003L06Rik	G	T	5: 87,971,689	V102L	probably benign	Het
Adck1	T	C	12: 88,402,084	Y111H	probably damaging	Het
Adcy10	G	T	1: 165,518,403	K340N	probably damaging	Het
Aebp1	T	C	11: 5,870,089	V355A	probably damaging	Het
Atp2b2	T	C	6: 113,774,201		probably benign	Het
Atrn	T	C	2: 130,957,080	V390A	probably benign	Het
Bpifc	T	A	10: 85,977,735	Q315L	probably benign	Het
C1qtnf6	T	G	15: 78,524,892		probably null	Het
Cab39l	A	G	14: 59,519,737		probably benign	Het
Capn12	T	A	7: 28,882,764		probably benign	Het
Ceacam18	A	C	7: 43,639,355	T177P	possibly damaging	Het
Ces5a	A	T	8: 93,525,665	F200I	probably damaging	Het
Cldn19	G	T	4: 119,257,051		probably null	Het
Cntnap2	A	G	6: 46,530,679	S46P	probably damaging	Het
Dchs1	A	G	7: 105,764,525	Y1028H	probably damaging	Het
Exd1	A	T	2: 119,524,674	F253L	probably damaging	Het
Fam161a	A	G	11: 23,015,826	N40D	possibly damaging	Het
Fam81a	A	T	9: 70,125,108	I34N	probably damaging	Het
Fchsd1	A	C	18: 37,965,897		probably null	Het
Fut11	T	A	14: 20,696,166	F359I	possibly damaging	Het
Fut7	T	C	2: 25,425,147	V92A	probably damaging	Het
Grid2	C	G	6: 64,429,754	F699L	possibly damaging	Het
Grin2a	A	G	16: 9,663,603	S445P	possibly damaging	Het
H2al2b	A	C	Y: 2,720,391	F95C	probably damaging	Het
Hecw2	T	C	1: 53,851,618	D1246G	probably damaging	Het
Ifit1	A	G	19: 34,647,632	N56S	probably damaging	Het
Ldb3	C	A	14: 34,555,356	V354L	probably benign	Het
Lrig2	T	C	3: 104,463,876	Y479C	probably benign	Het
Ltn1	A	G	16: 87,381,556	V1595A	probably damaging	Het
Macf1	A	G	4: 123,432,530	V2939A	possibly damaging	Het
Mapre3	T	G	5: 30,861,917	I35S	probably damaging	Het
Med16	A	T	10: 79,898,316	L588Q	probably damaging	Het
Ncapg2	T	C	12: 116,434,578		probably benign	Het
Ndst1	A	T	18: 60,698,504	I594N	probably damaging	Het
Ndst3	A	G	3: 123,548,906	I752T	possibly damaging	Het
Obscn	G	T	11: 59,115,855	S1185R	probably damaging	Het
Olfr1466	T	A	19: 13,342,122	C121*	probably null	Het
Olfr1500	A	T	19: 13,828,315	L27H	probably damaging	Het
Olfr303	A	G	7: 86,394,812	S229P	probably benign	Het
Otof	T	A	5: 30,379,556	D1285V	probably benign	Het
Pcnx2	A	G	8: 125,891,141	I125T	probably benign	Het
Pde4a	T	C	9: 21,201,247	S240P	probably damaging	Het
Pi15	T	C	1: 17,619,852	S126P	probably benign	Het
Pkhd1	T	C	1: 20,117,780	S3435G	probably damaging	Het
Plin1	C	A	7: 79,726,590	V133L	probably benign	Het
Pnpt1	T	A	11: 29,130,776	C7S	unknown	Het
Ppp3ca	A	T	3: 136,797,818	M51L	probably benign	Het
Primpol	G	T	8: 46,586,467		probably benign	Het
Prlr	T	C	15: 10,319,333	V116A	probably damaging	Het
Rnf139	A	G	15: 58,889,417	D35G	probably damaging	Het
Rsbn1l	T	A	5: 20,951,673	K38M	probably damaging	Het
Ryr3	T	A	2: 112,869,082	I888F	probably damaging	Het
Sec16a	C	A	2: 26,428,382	V1566F	probably damaging	Het
Sin3b	A	G	8: 72,753,287	T874A	probably benign	Het
Slc5a5	A	C	8: 70,892,334	Y110D	probably damaging	Het
Smarcd2	C	T	11: 106,267,152	V97I	probably benign	Het
St6galnac2	G	A	11: 116,684,487		probably benign	Het
Tbc1d22b	T	C	17: 29,570,611	L149P	probably damaging	Het
Tekt2	T	C	4: 126,323,649	I208V	probably benign	Het
Tenm3	A	G	8: 48,228,981	I2522T	possibly damaging	Het
Ttc37	T	A	13: 76,138,372	D891E	probably benign	Het
Ttll5	T	A	12: 85,864,568	Y233*	probably null	Het
Vcpip1	C	T	1: 9,724,502	E1215K	probably damaging	Het
Wdr4	T	C	17: 31,509,763		probably benign	Het
Zadh2	A	G	18: 84,094,706	E169G	probably benign	Het
Zfp703	G	A	8: 26,979,373	G355D	probably damaging	Het
Zfp830	T	A	11: 82,764,968	D199E	probably damaging	Het

Other mutations in Ncstn

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00737:Ncstn	APN	1	172074401	missense	probably benign	0.02
IGL02030:Ncstn	APN	1	172072457	splice site	probably benign
IGL02470:Ncstn	APN	1	172082599	critical splice donor site	probably null
IGL02498:Ncstn	APN	1	172068592	missense	probably benign
morel	UTSW	1	172072476	missense	probably damaging	0.99
Pig	UTSW	1	172071525	missense	probably damaging	1.00
truffle	UTSW	1	172070009	missense	probably damaging	1.00
R0048:Ncstn	UTSW	1	172069961	splice site	probably benign
R0480:Ncstn	UTSW	1	172082592	splice site	probably benign
R0648:Ncstn	UTSW	1	172067887	missense	probably benign	0.01
R0792:Ncstn	UTSW	1	172071505	missense	possibly damaging	0.95
R1330:Ncstn	UTSW	1	172071525	missense	probably damaging	1.00
R1660:Ncstn	UTSW	1	172066772	missense	possibly damaging	0.78
R1828:Ncstn	UTSW	1	172071471	frame shift	probably null
R1892:Ncstn	UTSW	1	172071471	frame shift	probably null
R1907:Ncstn	UTSW	1	172072143	missense	probably damaging	0.97
R3722:Ncstn	UTSW	1	172067895	missense	possibly damaging	0.50
R3876:Ncstn	UTSW	1	172070073	missense	probably benign	0.02
R3946:Ncstn	UTSW	1	172067494	missense	probably benign	0.00
R3969:Ncstn	UTSW	1	172070009	missense	probably damaging	1.00
R4108:Ncstn	UTSW	1	172072544	missense	probably damaging	1.00
R4597:Ncstn	UTSW	1	172068256	nonsense	probably null
R4998:Ncstn	UTSW	1	172071520	missense	possibly damaging	0.81
R5037:Ncstn	UTSW	1	172068626	missense	probably damaging	1.00
R5150:Ncstn	UTSW	1	172067584	intron	probably benign
R5406:Ncstn	UTSW	1	172072164	missense	probably benign	0.00
R5444:Ncstn	UTSW	1	172072839	missense	possibly damaging	0.92
R5605:Ncstn	UTSW	1	172081150	intron	probably benign
R6675:Ncstn	UTSW	1	172071528	missense	probably damaging	1.00
R7268:Ncstn	UTSW	1	172081263	missense	possibly damaging	0.86
R7290:Ncstn	UTSW	1	172072806	missense	probably benign
R7871:Ncstn	UTSW	1	172075456	missense	probably benign	0.00
R8238:Ncstn	UTSW	1	172072476	missense	probably damaging	0.99
R9462:Ncstn	UTSW	1	172072140	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- TTTGTGAAGGCTCAAAGCAAACACC -3'
(R):5'- ACATCTGTGGGACTAGAACCTGACG -3'

Sequencing Primer
(F):5'- TGTCACACCACAGGGACTG -3'
(R):5'- ACGTGCATTCTCTTGAAGCAG -3'

Posted On

2014-04-13