Mutagenetix > Incidental Mutation

Incidental Mutation 'R7268:Ncstn'

565048

Institutional Source

Beutler Lab

Gene Symbol

Ncstn

Ensembl Gene

ENSMUSG00000003458

Gene Name

nicastrin

Synonyms

D1Dau13e, 9430068N19Rik, Nct, nicastrin

MMRRC Submission

045319-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7268 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

171893580-171910356 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 171908830 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Alanine at position 46 (T46A)

Ref Sequence

ENSEMBL: ENSMUSP00000003550 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000003550] [ENSMUST00000027833] [ENSMUST00000124289] [ENSMUST00000135192] [ENSMUST00000140643] [ENSMUST00000146137]

AlphaFold

P57716

Predicted Effect

possibly damaging
Transcript: ENSMUST00000003550
AA Change: T46A

PolyPhen 2 Score 0.860 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000003550
Gene: ENSMUSG00000003458
AA Change: T46A

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

probably benign
Transcript: ENSMUST00000027833

SMART Domains

Protein: ENSMUSP00000027833
Gene: ENSMUSG00000026553

Domain	Start	End	E-Value	Type
WD40	2	37	2.86e0	SMART
WD40	40	79	1.11e-6	SMART
WD40	82	121	4.76e-6	SMART
WD40	124	163	2.24e-11	SMART
WD40	194	233	2.98e-7	SMART
WD40	238	277	8.42e-7	SMART
WD40	280	318	1.38e1	SMART
Pfam:Coatomer_WDAD	338	776	5.4e-144	PFAM
Pfam:COPI_C	824	1233	1.4e-190	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000124289

SMART Domains

Protein: ENSMUSP00000118899
Gene: ENSMUSG00000026553

Domain	Start	End	E-Value	Type
Blast:WD40	1	37	2e-19	BLAST
PDB:4J8G\|B	1	52	2e-23	PDB
SCOP:d1erja_	1	52	1e-6	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000135192

SMART Domains

Protein: ENSMUSP00000118179
Gene: ENSMUSG00000026553

Domain	Start	End	E-Value	Type
WD40	2	37	2.86e0	SMART
WD40	40	79	1.11e-6	SMART
WD40	82	121	4.76e-6	SMART
WD40	124	163	2.24e-11	SMART
WD40	194	233	2.98e-7	SMART
WD40	238	277	8.42e-7	SMART
WD40	280	318	1.38e1	SMART
Pfam:Coatomer_WDAD	338	767	1.1e-148	PFAM
Pfam:COPI_C	815	1224	3.6e-216	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000140643
AA Change: T46A

PolyPhen 2 Score 0.860 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000119128
Gene: ENSMUSG00000003458
AA Change: T46A

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000146137
AA Change: T46A

PolyPhen 2 Score 0.860 (Sensitivity: 0.83; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000120663
Gene: ENSMUSG00000003458
AA Change: T46A

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

Meta Mutation Damage Score

0.1755

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.7%

Validation Efficiency

99% (72/73)

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: 72 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Abl2	T	C	1: 156,461,509 (GRCm39)		probably null	Het
Acsf3	A	G	8: 123,517,401 (GRCm39)	Y399C	probably benign	Het
Acsm5	A	T	7: 119,136,511 (GRCm39)	T361S	probably benign	Het
Agap1	T	G	1: 89,694,070 (GRCm39)	I456S	probably benign	Het
Ahnak2	A	T	12: 112,780,802 (GRCm38)	V70E		Het
Alb	T	A	5: 90,610,575 (GRCm39)	S52T	probably benign	Het
Ankle1	A	G	8: 71,860,189 (GRCm39)	T256A	probably damaging	Het
Armt1	G	A	10: 4,400,855 (GRCm39)	V201M	possibly damaging	Het
Atp2a2	T	C	5: 122,605,792 (GRCm39)	T388A	probably benign	Het
Atp6v0a2	T	C	5: 124,796,930 (GRCm39)	L770P	probably damaging	Het
B4galnt3	A	T	6: 120,192,003 (GRCm39)	W578R	possibly damaging	Het
Babam2	T	C	5: 31,859,197 (GRCm39)	S2P	probably damaging	Het
Baz2a	A	G	10: 127,960,090 (GRCm39)	H1459R	possibly damaging	Het
Bbs7	C	T	3: 36,658,575 (GRCm39)	R233Q	probably benign	Het
Cacna2d1	G	A	5: 16,575,586 (GRCm39)	G1076R	probably damaging	Het
Camsap2	C	T	1: 136,201,483 (GRCm39)		probably null	Het
Car10	A	G	11: 93,490,077 (GRCm39)	N273D	probably benign	Het
Ccdc66	T	C	14: 27,208,880 (GRCm39)	D458G	probably benign	Het
Ccdc7a	T	A	8: 129,607,633 (GRCm39)	H982L	possibly damaging	Het
Col9a1	A	G	1: 24,246,479 (GRCm39)	K386E	possibly damaging	Het
Ctcfl	A	G	2: 172,949,588 (GRCm39)	I415T	probably benign	Het
Cyp3a16	G	C	5: 145,404,280 (GRCm39)	Y54*	probably null	Het
Dact2	T	C	17: 14,416,797 (GRCm39)	T468A	probably benign	Het
Dgkb	T	A	12: 38,197,554 (GRCm39)	L355*	probably null	Het
Dhx40	A	T	11: 86,697,442 (GRCm39)	C42S	possibly damaging	Het
Dnaaf9	C	A	2: 130,648,708 (GRCm39)	R258L	unknown	Het
Dop1a	G	T	9: 86,394,830 (GRCm39)	E637*	probably null	Het
Dpp4	G	T	2: 62,178,186 (GRCm39)	P649T	probably damaging	Het
Eri3	T	A	4: 117,506,580 (GRCm39)	I303K	probably benign	Het
Foxi1	A	T	11: 34,155,783 (GRCm39)	Y282*	probably null	Het
Gdi2	T	A	13: 3,606,363 (GRCm39)	Y146*	probably null	Het
Gns	A	G	10: 121,212,557 (GRCm39)	Y173C	probably damaging	Het
Gpc1	C	A	1: 92,786,093 (GRCm39)	P494Q	possibly damaging	Het
Habp2	G	T	19: 56,302,518 (GRCm39)	G274V	probably damaging	Het
Hcfc2	T	A	10: 82,544,846 (GRCm39)	Y159*	probably null	Het
Hmcn2	T	A	2: 31,347,978 (GRCm39)	S4875T	possibly damaging	Het
Hmgcs2	A	G	3: 98,204,796 (GRCm39)	N318S	probably benign	Het
Lnpep	A	T	17: 17,758,803 (GRCm39)	M847K	probably benign	Het
Mmp16	A	C	4: 18,093,366 (GRCm39)	M374L	probably benign	Het
Mrpl38	A	G	11: 116,029,396 (GRCm39)	I40T	possibly damaging	Het
Nlrp1a	C	T	11: 71,015,068 (GRCm39)	V61I	probably benign	Het
Npas2	G	T	1: 39,326,658 (GRCm39)	V48L	probably damaging	Het
Or13p5	A	G	4: 118,592,605 (GRCm39)	Y293C	probably damaging	Het
Or52ac1	G	A	7: 104,246,284 (GRCm39)	L35F	probably benign	Het
Or6c6	C	T	10: 129,187,263 (GRCm39)	T277I	possibly damaging	Het
Pcyox1	A	T	6: 86,368,713 (GRCm39)	N268K	possibly damaging	Het
Pramel14	A	T	4: 143,720,090 (GRCm39)		probably null	Het
Prr27	T	C	5: 87,991,135 (GRCm39)	L249P	probably damaging	Het
Psat1	A	T	19: 15,894,508 (GRCm39)	V168D	probably damaging	Het
Psg17	G	T	7: 18,548,586 (GRCm39)	T395K	possibly damaging	Het
Ptgis	A	G	2: 167,048,676 (GRCm39)	Y447H	probably benign	Het
Rad50	T	A	11: 53,575,102 (GRCm39)	N607I	probably benign	Het
Rps6ka2	T	C	17: 7,562,662 (GRCm39)	Y602H	possibly damaging	Het
Senp6	G	A	9: 80,049,406 (GRCm39)	R1010H	probably damaging	Het
Slc8a3	C	A	12: 81,361,827 (GRCm39)	D331Y	probably damaging	Het
Slc9c1	G	A	16: 45,370,479 (GRCm39)	S240N	probably damaging	Het
Slf1	A	G	13: 77,214,826 (GRCm39)	L620P	probably damaging	Het
Snx19	A	G	9: 30,351,473 (GRCm39)	E847G	probably damaging	Het
Spaca6	T	C	17: 18,052,369 (GRCm39)	V103A	probably benign	Het
Tbk1	A	G	10: 121,388,404 (GRCm39)	Y591H	probably benign	Het
Tchh	CTCCGCCGGGAGCAAGAGCTCCGCCGGGAGCAAGAGTTCCGCCGGGAGCAAGAGCTCCGCCGGGAGCAAGAGTTCCGCCGGGAGCAAGAGCTCCGCC	CTCCGCCGGGAGCAAGAGCTCCGCCGGGAGCAAGAGTTCCGCCGGGAGCAAGAGCTCCGCC	3: 93,354,015 (GRCm39)		probably benign	Het
Tfap2a	G	A	13: 40,882,236 (GRCm39)	T15I	possibly damaging	Het
Tgm2	G	A	2: 157,962,188 (GRCm39)	R544*	probably null	Het
Tmem116	T	A	5: 121,605,918 (GRCm39)	I90K		Het
Tmem30c	A	C	16: 57,086,777 (GRCm39)	L342R	probably damaging	Het
Trpm6	C	T	19: 18,755,949 (GRCm39)	T64I	probably benign	Het
Ttll8	A	G	15: 88,819,159 (GRCm39)		probably null	Het
Vcpip1	A	G	1: 9,816,307 (GRCm39)	I692T	probably damaging	Het
Vmn1r169	T	G	7: 23,276,853 (GRCm39)	F82V	probably benign	Het
Vmn1r178	G	A	7: 23,593,378 (GRCm39)	C142Y	probably benign	Het
Vmn2r16	T	A	5: 109,488,331 (GRCm39)	Y401*	probably null	Het
Wdr91	A	G	6: 34,869,375 (GRCm39)	V383A	probably benign	Het

Other mutations in Ncstn

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00737:Ncstn	APN	1	171,901,968 (GRCm39)	missense	probably benign	0.02
IGL02030:Ncstn	APN	1	171,900,024 (GRCm39)	splice site	probably benign
IGL02470:Ncstn	APN	1	171,910,166 (GRCm39)	critical splice donor site	probably null
IGL02498:Ncstn	APN	1	171,896,159 (GRCm39)	missense	probably benign
morel	UTSW	1	171,900,043 (GRCm39)	missense	probably damaging	0.99
Pig	UTSW	1	171,899,092 (GRCm39)	missense	probably damaging	1.00
truffle	UTSW	1	171,897,576 (GRCm39)	missense	probably damaging	1.00
R0048:Ncstn	UTSW	1	171,897,528 (GRCm39)	splice site	probably benign
R0480:Ncstn	UTSW	1	171,910,159 (GRCm39)	splice site	probably benign
R0648:Ncstn	UTSW	1	171,895,454 (GRCm39)	missense	probably benign	0.01
R0792:Ncstn	UTSW	1	171,899,072 (GRCm39)	missense	possibly damaging	0.95
R1330:Ncstn	UTSW	1	171,899,092 (GRCm39)	missense	probably damaging	1.00
R1524:Ncstn	UTSW	1	171,899,716 (GRCm39)	missense	possibly damaging	0.58
R1660:Ncstn	UTSW	1	171,894,339 (GRCm39)	missense	possibly damaging	0.78
R1828:Ncstn	UTSW	1	171,899,038 (GRCm39)	frame shift	probably null
R1892:Ncstn	UTSW	1	171,899,038 (GRCm39)	frame shift	probably null
R1907:Ncstn	UTSW	1	171,899,710 (GRCm39)	missense	probably damaging	0.97
R3722:Ncstn	UTSW	1	171,895,462 (GRCm39)	missense	possibly damaging	0.50
R3876:Ncstn	UTSW	1	171,897,640 (GRCm39)	missense	probably benign	0.02
R3946:Ncstn	UTSW	1	171,895,061 (GRCm39)	missense	probably benign	0.00
R3969:Ncstn	UTSW	1	171,897,576 (GRCm39)	missense	probably damaging	1.00
R4108:Ncstn	UTSW	1	171,900,111 (GRCm39)	missense	probably damaging	1.00
R4597:Ncstn	UTSW	1	171,895,823 (GRCm39)	nonsense	probably null
R4998:Ncstn	UTSW	1	171,899,087 (GRCm39)	missense	possibly damaging	0.81
R5037:Ncstn	UTSW	1	171,896,193 (GRCm39)	missense	probably damaging	1.00
R5150:Ncstn	UTSW	1	171,895,151 (GRCm39)	intron	probably benign
R5406:Ncstn	UTSW	1	171,899,731 (GRCm39)	missense	probably benign	0.00
R5444:Ncstn	UTSW	1	171,900,406 (GRCm39)	missense	possibly damaging	0.92
R5605:Ncstn	UTSW	1	171,908,717 (GRCm39)	intron	probably benign
R6675:Ncstn	UTSW	1	171,899,095 (GRCm39)	missense	probably damaging	1.00
R7290:Ncstn	UTSW	1	171,900,373 (GRCm39)	missense	probably benign
R7871:Ncstn	UTSW	1	171,903,023 (GRCm39)	missense	probably benign	0.00
R8238:Ncstn	UTSW	1	171,900,043 (GRCm39)	missense	probably damaging	0.99
R9462:Ncstn	UTSW	1	171,899,707 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- GGTTTGACAGATGATAATCACCTTC -3'
(R):5'- TTCCAATAATGTGGCCAAGAAGTG -3'

Sequencing Primer
(F):5'- ATGCCAAGACTCCTAAGC -3'
(R):5'- TGGCCAAGAAGTGAAAAGAATGATC -3'

Posted On

2019-06-26