Incidental Mutation 'R3942:Aph1a'
ID 312895
Institutional Source Beutler Lab
Gene Symbol Aph1a
Ensembl Gene ENSMUSG00000015750
Gene Name aph1 homolog A, gamma secretase subunit
Synonyms 6530402N02Rik
Accession Numbers
Essential gene? Essential (E-score: 1.000) question?
Stock # R3942 (G1)
Quality Score 225
Status Not validated
Chromosome 3
Chromosomal Location 95801281-95805600 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 95801573 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Arginine to Tryptophan at position 31 (R31W)
Ref Sequence ENSEMBL: ENSMUSP00000142972 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000015894] [ENSMUST00000036181] [ENSMUST00000036360] [ENSMUST00000056710] [ENSMUST00000090476] [ENSMUST00000197081] [ENSMUST00000171519]
AlphaFold Q8BVF7
Predicted Effect possibly damaging
Transcript: ENSMUST00000015894
AA Change: R31W

PolyPhen 2 Score 0.873 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000015894
Gene: ENSMUSG00000015750
AA Change: R31W

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 possibly damaging
Transcript: ENSMUST00000056710
AA Change: R31W

PolyPhen 2 Score 0.873 (Sensitivity: 0.83; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000058846
Gene: ENSMUSG00000015750
AA Change: R31W

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 probably damaging
Transcript: ENSMUST00000197081
AA Change: R31W

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
Predicted Effect noncoding transcript
Transcript: ENSMUST00000197232
Predicted Effect noncoding transcript
Transcript: ENSMUST00000145949
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: 99.2%
  • 3x: 98.6%
  • 10x: 97.2%
  • 20x: 94.9%
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: 26 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adgrv1 T C 13: 81,330,908 (GRCm39) N6049S probably damaging Het
Atp10b T C 11: 43,063,581 (GRCm39) V172A probably damaging Het
Atp13a2 T C 4: 140,733,733 (GRCm39) S1041P probably damaging Het
Best3 T A 10: 116,824,579 (GRCm39) F15Y possibly damaging Het
Brinp3 C A 1: 146,627,599 (GRCm39) D277E probably damaging Het
Crb1 A C 1: 139,265,211 (GRCm39) L69R possibly damaging Het
Crcp T C 5: 130,063,791 (GRCm39) probably null Het
Dysf G A 6: 84,163,491 (GRCm39) probably null Het
Hps3 T C 3: 20,051,103 (GRCm39) Y859C probably damaging Het
Irx5 C A 8: 93,086,314 (GRCm39) N132K probably damaging Het
Itgb2 A G 10: 77,393,867 (GRCm39) T436A probably benign Het
Kit A G 5: 75,769,978 (GRCm39) D130G probably benign Het
Krt12 A G 11: 99,312,922 (GRCm39) S41P unknown Het
Lypd6b G T 2: 49,833,552 (GRCm39) S64I probably damaging Het
Mpc1 T A 17: 8,507,420 (GRCm39) probably null Het
Or4c109 T A 2: 88,818,455 (GRCm39) L30F probably benign Het
Or5b95 A T 19: 12,657,768 (GRCm39) M99L probably benign Het
Pard3b T A 1: 62,198,611 (GRCm39) I233N probably damaging Het
Pcdh1 A G 18: 38,332,511 (GRCm39) V164A probably benign Het
Pclo A G 5: 14,729,932 (GRCm39) probably benign Het
Pkhd1l1 T C 15: 44,455,422 (GRCm39) probably null Het
Slco1a7 A G 6: 141,673,440 (GRCm39) I366T probably damaging Het
Spata31d1d T C 13: 59,875,276 (GRCm39) Q753R probably benign Het
Stxbp6 A G 12: 44,949,641 (GRCm39) probably null Het
Trav6-5 T C 14: 53,728,838 (GRCm39) S32P probably benign Het
Zp3r A C 1: 130,504,791 (GRCm39) D470E possibly damaging 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
R2356:Aph1a UTSW 3 95,801,544 (GRCm39) missense probably benign 0.24
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'- GTATTCATTGGCCTTCCGGG -3'
(R):5'- GCGGGAAATTCTCCTAGATCACG -3'

Sequencing Primer
(F):5'- TTCCGTAGACGAGGTCGG -3'
(R):5'- AGATCACGATTTGACCCTGTG -3'
Posted On 2015-04-30