Incidental Mutation 'R2356:Aph1a'
ID 246914
Institutional Source Beutler Lab
Gene Symbol Aph1a
Ensembl Gene ENSMUSG00000015750
Gene Name aph1 homolog A, gamma secretase subunit
Synonyms 6530402N02Rik
MMRRC Submission 040338-MU
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R2356 (G1)
Quality Score 164
Status Not validated
Chromosome 3
Chromosomal Location 95801281-95805600 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) T to C at 95801544 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Phenylalanine to Serine at position 21 (F21S)
Ref Sequence ENSEMBL: ENSMUSP00000142972 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000015894] [ENSMUST00000036181] [ENSMUST00000036360] [ENSMUST00000056710] [ENSMUST00000090476] [ENSMUST00000197081] [ENSMUST00000171519]
AlphaFold Q8BVF7
Predicted Effect probably benign
Transcript: ENSMUST00000015894
AA Change: F21S

PolyPhen 2 Score 0.096 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000015894
Gene: ENSMUSG00000015750
AA Change: F21S

DomainStartEndE-ValueType
Pfam:Aph-1 2 246 7.3e-98 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000036181
SMART Domains Protein: ENSMUSP00000036983
Gene: ENSMUSG00000038526

DomainStartEndE-ValueType
Carb_anhydrase 22 278 2.43e-123 SMART
transmembrane domain 290 312 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000036360
SMART Domains Protein: ENSMUSP00000046810
Gene: ENSMUSG00000038543

DomainStartEndE-ValueType
Pfam:DUF4634 1 145 3.6e-64 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000056710
AA Change: F21S

PolyPhen 2 Score 0.096 (Sensitivity: 0.93; Specificity: 0.85)
SMART Domains Protein: ENSMUSP00000058846
Gene: ENSMUSG00000015750
AA Change: F21S

DomainStartEndE-ValueType
Pfam:Aph-1 2 239 1.2e-96 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000090476
SMART Domains Protein: ENSMUSP00000102749
Gene: ENSMUSG00000038543

DomainStartEndE-ValueType
Pfam:DUF4634 1 146 1.8e-65 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000133611
Predicted Effect noncoding transcript
Transcript: ENSMUST00000145949
Predicted Effect probably benign
Transcript: ENSMUST00000197081
AA Change: F21S

PolyPhen 2 Score 0.239 (Sensitivity: 0.91; Specificity: 0.88)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000197232
Predicted Effect probably benign
Transcript: ENSMUST00000171519
SMART Domains Protein: ENSMUSP00000127666
Gene: ENSMUSG00000038543

DomainStartEndE-ValueType
Pfam:DUF4634 1 146 1.5e-65 PFAM
Coding Region Coverage
  • 1x: 99.3%
  • 3x: 98.7%
  • 10x: 97.5%
  • 20x: 95.7%
Validation Efficiency
MGI Phenotype FUNCTION: This gene encodes a subunit of the gamma-secretase complex, which is localized to the endoplasmic reticulum and golgi apparatus. Gamma-secretase is a multi-protein enzyme that catalyzes intramembraneous proteolysis of type I transmembrane proteins and is essential for many signaling pathways, including the Notch signaling pathway. Studies suggest that the protein encoded by this locus binds directly to substrates of the gamma-secretase complex, including the beta-amyloid precursor protein which is associated with Alzheimer disease progression. This gene is required for normal embryonic development and survival, and disruption is associated with defects in the yolk sack angiogenesis, neural tube formation, and somitogenesis. A pseudogene of this gene is located on chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]
PHENOTYPE: Homozygous null embryos die by E11, are severely growth retarded by E9.5 and display defects in somite patterning, branchial arch and heart chamber development, vascular morphogenesis of the yolk sac and have distended pericardial sacs. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 64 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Abcf3 G T 16: 20,379,249 (GRCm39) R705L probably benign Het
Adcy6 A T 15: 98,494,897 (GRCm39) probably null Het
Ank1 A T 8: 23,575,688 (GRCm39) T145S probably damaging Het
Apoa5 T A 9: 46,181,341 (GRCm39) V139E probably damaging Het
Arhgap44 T C 11: 64,900,851 (GRCm39) K595R probably damaging Het
Arhgap5 C T 12: 52,565,930 (GRCm39) P967L probably benign Het
Atp13a5 A T 16: 29,099,887 (GRCm39) I683N probably damaging Het
Cdc6 A G 11: 98,810,118 (GRCm39) T476A probably benign Het
Cdk10 T C 8: 123,955,908 (GRCm39) V199A probably damaging Het
Ces2h G A 8: 105,742,570 (GRCm39) C94Y probably damaging Het
Clcn1 G A 6: 42,268,559 (GRCm39) G155D probably damaging Het
Cxcr4 A G 1: 128,517,251 (GRCm39) Y135H probably damaging Het
Dapp1 A G 3: 137,643,510 (GRCm39) V184A possibly damaging Het
Dhrs7 A C 12: 72,699,155 (GRCm39) S276A probably benign Het
Dlg5 A G 14: 24,220,496 (GRCm39) probably null Het
Dnaaf1 T A 8: 120,315,026 (GRCm39) F278Y probably damaging Het
Dnaaf2 A G 12: 69,244,992 (GRCm39) F23S probably benign Het
En2 G T 5: 28,371,330 (GRCm39) probably benign Het
Erbb4 T A 1: 68,117,755 (GRCm39) M887L probably benign Het
Exoc5 T C 14: 49,253,738 (GRCm39) M482V probably benign Het
Foxk1 A G 5: 142,441,164 (GRCm39) I571V possibly damaging Het
Fry G A 5: 150,394,897 (GRCm39) G650D probably benign Het
Gm8225 T C 17: 26,762,378 (GRCm39) S190P probably damaging Het
Gpx5 G C 13: 21,475,538 (GRCm39) H63D possibly damaging Het
Ipo9 A T 1: 135,334,555 (GRCm39) S285T probably benign Het
Itga8 T C 2: 12,204,952 (GRCm39) H495R probably benign Het
Klf11 T C 12: 24,703,582 (GRCm39) S6P probably damaging Het
Krtap8-1 A T 16: 89,284,789 (GRCm39) Y3N possibly damaging Het
Krtap8-1 G T 16: 89,284,790 (GRCm39) Y2* probably null Het
Lama1 T A 17: 68,117,109 (GRCm39) L2468Q probably damaging Het
Lmo7 T C 14: 102,124,381 (GRCm39) L280S probably damaging Het
Matk G A 10: 81,097,377 (GRCm39) probably null Het
Mcmdc2 A G 1: 10,001,026 (GRCm39) T434A possibly damaging Het
Mst1r T A 9: 107,795,069 (GRCm39) L1283Q probably damaging Het
Muc21 A G 17: 35,932,563 (GRCm39) probably benign Het
Nbn T A 4: 15,970,863 (GRCm39) I282N probably damaging Het
Ncln A G 10: 81,328,756 (GRCm39) V174A probably benign Het
Nipa2 G A 7: 55,582,714 (GRCm39) H344Y probably benign Het
Nlrp4g A G 9: 124,349,306 (GRCm38) noncoding transcript Het
Or56b1 G T 7: 104,285,834 (GRCm39) E318* probably null Het
Or6c38 T C 10: 128,929,761 (GRCm39) I27M probably benign Het
Pik3r5 T C 11: 68,383,743 (GRCm39) S521P probably damaging Het
Pkhd1l1 C T 15: 44,396,415 (GRCm39) T1979M probably benign Het
Plekhn1 T G 4: 156,307,158 (GRCm39) D464A probably damaging Het
Ppp4r1 T A 17: 66,140,045 (GRCm39) Y648N probably damaging Het
Prkaa2 C T 4: 104,896,918 (GRCm39) probably null Het
Prkdc T A 16: 15,502,068 (GRCm39) H828Q probably benign Het
Prss40 A T 1: 34,598,984 (GRCm39) Y69* probably null Het
Prx C T 7: 27,207,284 (GRCm39) probably benign Het
Psmd11 T A 11: 80,319,530 (GRCm39) S7T possibly damaging Het
Psmd14 A T 2: 61,630,351 (GRCm39) H287L probably benign Het
Rcor1 T C 12: 111,076,226 (GRCm39) Y297H probably damaging Het
Rnf40 T G 7: 127,190,748 (GRCm39) V272G probably damaging Het
Serpina3f G T 12: 104,183,626 (GRCm39) E163* probably null Het
Setd4 G A 16: 93,387,871 (GRCm39) T205I probably damaging Het
Shroom1 A T 11: 53,357,274 (GRCm39) T646S probably benign Het
Smg8 G C 11: 86,976,554 (GRCm39) S342R probably benign Het
Spata31h1 A G 10: 82,119,789 (GRCm39) V4407A possibly damaging Het
Trhde T C 10: 114,237,421 (GRCm39) Y986C probably damaging Het
Tulp2 A T 7: 45,168,052 (GRCm39) T155S possibly damaging Het
Vmn1r212 A T 13: 23,068,120 (GRCm39) L71* probably null Het
Wnk2 A T 13: 49,192,644 (GRCm39) C2032* probably null Het
Zfp429 A G 13: 67,538,746 (GRCm39) Y233H probably benign Het
Zfp809 C A 9: 22,154,336 (GRCm39) T351K probably benign Het
Other mutations in Aph1a
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02103:Aph1a APN 3 95,803,125 (GRCm39) missense probably damaging 0.99
R1675:Aph1a UTSW 3 95,802,211 (GRCm39) missense possibly damaging 0.96
R1735:Aph1a UTSW 3 95,802,821 (GRCm39) missense probably damaging 1.00
R1872:Aph1a UTSW 3 95,802,876 (GRCm39) missense probably damaging 1.00
R3942:Aph1a UTSW 3 95,801,573 (GRCm39) missense probably damaging 1.00
R4654:Aph1a UTSW 3 95,803,088 (GRCm39) missense probably benign 0.01
R4989:Aph1a UTSW 3 95,802,843 (GRCm39) missense probably damaging 1.00
R5134:Aph1a UTSW 3 95,802,843 (GRCm39) missense probably damaging 1.00
R5184:Aph1a UTSW 3 95,803,051 (GRCm39) splice site probably null
R6603:Aph1a UTSW 3 95,802,808 (GRCm39) missense probably damaging 1.00
R6650:Aph1a UTSW 3 95,803,598 (GRCm39) missense probably benign 0.28
R8157:Aph1a UTSW 3 95,802,150 (GRCm39) missense possibly damaging 0.64
Predicted Primers PCR Primer
(F):5'- TATTCATTGGCCTTCCGGGG -3'
(R):5'- ATTTGACCCTGTGTCCAACC -3'

Sequencing Primer
(F):5'- TTCCGTAGACGAGGTCGG -3'
(R):5'- TGTGTCCAACCTTTTCCGAC -3'
Posted On 2014-10-30