Incidental Mutation 'R4998:Ncstn'
ID 389610
Institutional Source Beutler Lab
Gene Symbol Ncstn
Ensembl Gene ENSMUSG00000003458
Gene Name nicastrin
Synonyms D1Dau13e, 9430068N19Rik, Nct, nicastrin
MMRRC Submission 042592-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R4998 (G1)
Quality Score 225
Status Validated
Chromosome 1
Chromosomal Location 171893580-171910356 bp(-) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to A at 171899087 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Asparagine to Isoleucine at position 348 (N348I)
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: N348I

PolyPhen 2 Score 0.814 (Sensitivity: 0.84; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000003550
Gene: ENSMUSG00000003458
AA Change: N348I

DomainStartEndE-ValueType
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

DomainStartEndE-ValueType
signal peptide 1 32 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000146137
SMART Domains Protein: ENSMUSP00000120663
Gene: ENSMUSG00000003458

DomainStartEndE-ValueType
signal peptide 1 32 N/A INTRINSIC
Meta Mutation Damage Score 0.1795 question?
Coding Region Coverage
  • 1x: 99.1%
  • 3x: 98.4%
  • 10x: 96.6%
  • 20x: 93.3%
Validation Efficiency 97% (91/94)
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: 86 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2310022A10Rik T C 7: 27,271,088 (GRCm39) V135A probably damaging Het
Ankrd42 T C 7: 92,273,282 (GRCm39) N115S possibly damaging Het
Baz1a T C 12: 55,021,922 (GRCm39) E120G probably damaging Het
Calcrl A T 2: 84,169,658 (GRCm39) V341E probably damaging Het
Card6 T C 15: 5,129,564 (GRCm39) R611G probably benign Het
Cd70 A T 17: 57,453,311 (GRCm39) S118T probably damaging Het
Chil5 T A 3: 105,927,248 (GRCm39) I188F probably damaging Het
Clca4b C T 3: 144,621,269 (GRCm39) V602I probably benign Het
Cldn10 G A 14: 119,025,725 (GRCm39) G53S possibly damaging Het
Col6a4 A G 9: 105,867,977 (GRCm39) probably benign Het
Cox8b T C 7: 140,479,001 (GRCm39) E38G probably damaging Het
Cx3cl1 C G 8: 95,507,053 (GRCm39) L353V probably damaging Het
Cyp2a4 G T 7: 26,006,786 (GRCm39) Q48H probably damaging Het
Defb8 T C 8: 19,497,603 (GRCm39) I3V probably benign Het
Dip2a A T 10: 76,155,390 (GRCm39) L65* probably null Het
Dnaaf4 A G 9: 72,867,960 (GRCm39) T74A possibly damaging Het
Dsg2 A T 18: 20,734,578 (GRCm39) D852V probably benign Het
Edar T C 10: 58,441,915 (GRCm39) R326G probably damaging Het
Egfr A G 11: 16,831,493 (GRCm39) E554G possibly damaging Het
Eif2b3 A C 4: 116,923,589 (GRCm39) K268T probably benign Het
Enox1 A T 14: 77,738,875 (GRCm39) probably benign Het
Enpp3 C A 10: 24,683,436 (GRCm39) M260I probably benign Het
Espn A T 4: 152,220,040 (GRCm39) M361K possibly damaging Het
Fam107a T C 14: 8,299,514 (GRCm38) N108S possibly damaging Het
Fbn2 A T 18: 58,205,703 (GRCm39) V1125D probably damaging Het
Fbxo30 T A 10: 11,166,507 (GRCm39) S410T probably damaging Het
Fchsd1 C T 18: 38,092,926 (GRCm39) probably benign Het
Fcsk G A 8: 111,614,435 (GRCm39) A618V probably damaging Het
Gm10715 T G 9: 3,038,073 (GRCm39) probably benign Het
Gm10722 A C 9: 3,001,041 (GRCm39) Y39S probably benign Het
Gm17416 C A 2: 152,411,427 (GRCm39) P57Q probably damaging Het
Gm27013 A T 6: 130,653,501 (GRCm39) C654S probably damaging Het
Gon4l G T 3: 88,807,305 (GRCm39) E1666D probably damaging Het
Gypa T A 8: 81,222,964 (GRCm39) S23T unknown Het
Gys1 C A 7: 45,100,968 (GRCm39) probably benign Het
Hdac10 T A 15: 89,008,143 (GRCm39) Q569L possibly damaging Het
Icos A G 1: 61,032,941 (GRCm39) T47A possibly damaging Het
Igfn1 T A 1: 135,882,404 (GRCm39) I2814F probably damaging Het
Kif27 A G 13: 58,440,957 (GRCm39) S1153P probably damaging Het
Lin28a A C 4: 133,746,028 (GRCm39) F9V possibly damaging Het
Lrriq3 T A 3: 154,893,695 (GRCm39) N465K probably benign Het
Lsm14a T C 7: 34,074,799 (GRCm39) E47G probably damaging Het
Mmel1 A G 4: 154,969,967 (GRCm39) K177R probably benign Het
Ninl A G 2: 150,795,284 (GRCm39) I619T probably damaging Het
Npb T C 11: 120,499,401 (GRCm39) Y23H probably damaging Het
Npepps A G 11: 97,096,933 (GRCm39) probably benign Het
Or8k30 T C 2: 86,339,699 (GRCm39) Y299H probably benign Het
Otop1 G A 5: 38,451,892 (GRCm39) probably null Het
Pcdha1 T C 18: 37,065,469 (GRCm39) L711P probably damaging Het
Pcyt1a A G 16: 32,270,660 (GRCm39) probably benign Het
Pdpr G T 8: 111,841,400 (GRCm39) V211F probably damaging Het
Pip4k2b T C 11: 97,613,261 (GRCm39) N245S possibly damaging Het
Platr26 G A 2: 71,561,214 (GRCm39) noncoding transcript Het
Plek A G 11: 16,933,194 (GRCm39) probably null Het
Potefam3c G C 8: 69,906,010 (GRCm39) N13K probably benign Het
Prdm15 A T 16: 97,595,689 (GRCm39) D1046E probably damaging Het
Prr29 T G 11: 106,267,779 (GRCm39) C175G probably benign Het
Ptpru A G 4: 131,504,196 (GRCm39) V1097A probably damaging Het
Ramp2 T A 11: 101,138,247 (GRCm39) probably benign Het
Rap1gap A G 4: 137,455,595 (GRCm39) D381G possibly damaging Het
Rbbp6 T A 7: 122,589,549 (GRCm39) D412E probably benign Het
Rgs4 C T 1: 169,572,802 (GRCm39) V45I probably benign Het
Ryr2 C T 13: 11,658,781 (GRCm39) R3614Q probably damaging Het
Shc3 G A 13: 51,596,856 (GRCm39) probably null Het
Shmt2 A T 10: 127,354,139 (GRCm39) C412S probably damaging Het
Slc25a45 A T 19: 5,934,945 (GRCm39) N265Y probably damaging Het
Slc4a10 G C 2: 62,074,783 (GRCm39) E316Q probably benign Het
Slc5a8 T C 10: 88,743,919 (GRCm39) probably null Het
Snx31 A G 15: 36,539,513 (GRCm39) V121A probably damaging Het
Socs3 T C 11: 117,858,542 (GRCm39) E172G probably damaging Het
Tg A G 15: 66,545,899 (GRCm39) D207G probably damaging Het
Them4 G T 3: 94,237,088 (GRCm39) V183F probably damaging Het
Tkt G A 14: 30,287,499 (GRCm39) W136* probably null Het
Tlcd3b C T 7: 126,426,795 (GRCm39) R73C probably damaging Het
Tmc3 C A 7: 83,271,529 (GRCm39) R894S probably benign Het
Tmem132a G T 19: 10,836,305 (GRCm39) P742T probably benign Het
Tmem202 A G 9: 59,432,129 (GRCm39) L66P probably damaging Het
Trbc1 G A 6: 41,516,270 (GRCm39) probably benign Het
Trhr2 A G 8: 123,085,511 (GRCm39) F158L probably benign Het
Ttc13 A T 8: 125,406,795 (GRCm39) N595K probably damaging Het
Ucp1 A G 8: 84,024,484 (GRCm39) probably null Het
Zbtb4 C T 11: 69,669,497 (GRCm39) T740I probably benign Het
Zfp69 A T 4: 120,804,522 (GRCm39) D116E possibly damaging Het
Zfp879 A G 11: 50,728,796 (GRCm39) L66S probably damaging Het
Zfp955b T A 17: 33,524,125 (GRCm39) probably benign Het
Zfyve1 T C 12: 83,594,839 (GRCm39) I718V possibly damaging Het
Other mutations in Ncstn
AlleleSourceChrCoordTypePredicted EffectPPH 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
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'- CATGTATGGTCTGTCTAGGACAC -3'
(R):5'- GCCCAAGAAATCCCATGGTG -3'

Sequencing Primer
(F):5'- TCTGTCTAGGACACAGACGTC -3'
(R):5'- GAAATCCCATGGTGCATACATG -3'
Posted On 2016-06-06