Incidental Mutation 'R3876:Ncstn'
| ID |
276827 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Ncstn
|
| Ensembl Gene |
ENSMUSG00000003458 |
| Gene Name |
nicastrin |
| Synonyms |
D1Dau13e, 9430068N19Rik, Nct, nicastrin |
| MMRRC Submission |
041606-MU
|
| Accession Numbers |
|
| Essential gene? |
Essential
(E-score: 1.000)
|
| Stock # |
R3876 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
1 |
| Chromosomal Location |
171893580-171910356 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to G
at 171897640 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Serine to Proline
at position 418
(S418P)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000003550
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000003550]
[ENSMUST00000140643]
[ENSMUST00000146137]
|
| AlphaFold |
P57716 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000003550
AA Change: S418P
PolyPhen 2
Score 0.022 (Sensitivity: 0.95; Specificity: 0.81)
|
| SMART Domains |
Protein: ENSMUSP00000003550
Gene: ENSMUSG00000003458
AA Change: S418P
| 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 |
0.0757 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.7%
- 10x: 97.5%
- 20x: 95.9%
|
| Validation Efficiency |
100% (53/53) |
| 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: 50 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 4931414P19Rik |
G |
A |
14: 54,828,857 (GRCm39) |
R215* |
probably null |
Het |
| Brinp2 |
C |
A |
1: 158,074,416 (GRCm39) |
L568F |
probably damaging |
Het |
| Brip1 |
T |
C |
11: 86,043,616 (GRCm39) |
Y316C |
probably damaging |
Het |
| Cdk5rap2 |
ATGTG |
ATG |
4: 70,208,214 (GRCm39) |
|
probably null |
Het |
| Cfap69 |
G |
T |
5: 5,634,645 (GRCm39) |
|
probably benign |
Het |
| Chrnb4 |
T |
C |
9: 54,951,182 (GRCm39) |
E27G |
probably damaging |
Het |
| Clec14a |
A |
G |
12: 58,315,430 (GRCm39) |
V64A |
possibly damaging |
Het |
| Crygs |
A |
G |
16: 22,625,262 (GRCm39) |
Y60H |
probably damaging |
Het |
| Dpp10 |
T |
A |
1: 123,281,216 (GRCm39) |
Q611L |
probably damaging |
Het |
| Entpd1 |
T |
C |
19: 40,725,264 (GRCm39) |
L450P |
probably damaging |
Het |
| Eogt |
G |
A |
6: 97,097,151 (GRCm39) |
S317L |
probably damaging |
Het |
| Exosc10 |
T |
A |
4: 148,657,376 (GRCm39) |
S584T |
probably benign |
Het |
| Fam184a |
C |
T |
10: 53,575,157 (GRCm39) |
V151I |
probably damaging |
Het |
| Fbxo43 |
A |
G |
15: 36,152,258 (GRCm39) |
V517A |
probably damaging |
Het |
| Flii |
T |
C |
11: 60,610,698 (GRCm39) |
T533A |
possibly damaging |
Het |
| Frmpd1 |
T |
G |
4: 45,284,093 (GRCm39) |
H971Q |
probably benign |
Het |
| Gata3 |
A |
T |
2: 9,867,954 (GRCm39) |
N333K |
probably damaging |
Het |
| Hectd1 |
A |
G |
12: 51,815,513 (GRCm39) |
S1525P |
probably damaging |
Het |
| Ibtk |
A |
G |
9: 85,600,479 (GRCm39) |
I816T |
probably benign |
Het |
| Kirrel1 |
C |
T |
3: 86,996,458 (GRCm39) |
M380I |
probably null |
Het |
| Krt34 |
T |
C |
11: 99,931,791 (GRCm39) |
T143A |
probably benign |
Het |
| Lipn |
G |
T |
19: 34,046,828 (GRCm39) |
M43I |
probably benign |
Het |
| Lrp1b |
A |
G |
2: 41,335,206 (GRCm39) |
C779R |
probably damaging |
Het |
| Mios |
G |
A |
6: 8,233,189 (GRCm39) |
R779Q |
probably damaging |
Het |
| Mme |
A |
T |
3: 63,269,480 (GRCm39) |
|
probably benign |
Het |
| Oprk1 |
T |
A |
1: 5,672,884 (GRCm39) |
C340* |
probably null |
Het |
| Or10d1c |
T |
A |
9: 38,894,166 (GRCm39) |
Y58F |
probably damaging |
Het |
| Or4c29 |
T |
C |
2: 88,739,952 (GRCm39) |
T262A |
possibly damaging |
Het |
| Or4k39 |
T |
C |
2: 111,238,967 (GRCm39) |
V69A |
possibly damaging |
Het |
| Or6c210 |
C |
T |
10: 129,496,143 (GRCm39) |
P156L |
probably benign |
Het |
| Or6z7 |
G |
A |
7: 6,484,131 (GRCm39) |
A8V |
probably benign |
Het |
| Pald1 |
T |
A |
10: 61,183,266 (GRCm39) |
N323Y |
probably damaging |
Het |
| Pcdhac1 |
C |
A |
18: 37,224,945 (GRCm39) |
A586E |
probably damaging |
Het |
| Pcnx2 |
C |
T |
8: 126,614,897 (GRCm39) |
A185T |
probably benign |
Het |
| Pik3r1 |
G |
A |
13: 101,821,465 (GRCm39) |
H430Y |
probably benign |
Het |
| Polr3b |
G |
A |
10: 84,556,382 (GRCm39) |
|
probably null |
Het |
| Prl8a6 |
A |
T |
13: 27,617,015 (GRCm39) |
L225* |
probably null |
Het |
| Psme4 |
T |
C |
11: 30,806,068 (GRCm39) |
S89P |
probably damaging |
Het |
| Pygl |
G |
A |
12: 70,248,113 (GRCm39) |
T250I |
probably damaging |
Het |
| Rgs13 |
T |
A |
1: 144,016,528 (GRCm39) |
K72* |
probably null |
Het |
| Ryr2 |
T |
A |
13: 11,603,045 (GRCm39) |
I4514F |
probably damaging |
Het |
| Septin3 |
A |
T |
15: 82,170,002 (GRCm39) |
D32V |
probably damaging |
Het |
| Sfrp2 |
C |
T |
3: 83,674,335 (GRCm39) |
P163S |
possibly damaging |
Het |
| Spata31 |
A |
G |
13: 65,068,745 (GRCm39) |
T298A |
probably benign |
Het |
| Stxbp2 |
T |
C |
8: 3,683,369 (GRCm39) |
|
probably null |
Het |
| Syne1 |
A |
T |
10: 5,002,345 (GRCm39) |
M282K |
possibly damaging |
Het |
| Timd2 |
T |
C |
11: 46,561,847 (GRCm39) |
|
probably null |
Het |
| Tlr11 |
G |
A |
14: 50,600,611 (GRCm39) |
V866I |
probably benign |
Het |
| Trappc10 |
T |
C |
10: 78,056,020 (GRCm39) |
|
probably null |
Het |
| Zfp512b |
AG |
AGG |
2: 181,230,556 (GRCm39) |
|
probably null |
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 |
|
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 |
|
R7268:Ncstn
|
UTSW |
1 |
171,908,830 (GRCm39) |
missense |
possibly damaging |
0.86 |
|
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'- AGACAGCATTCTTCCTCCAC -3'
(R):5'- TTGCCCATAGATGTGGAAAGC -3'
Sequencing Primer
(F):5'- TTCTTCCTCCACACTACAGAATAG -3'
(R):5'- CTCCTAACTTGGGAACTATAGGAAG -3'
|
| Posted On |
2015-04-06 |
Incidental Mutation