Mutagenetix > Incidental Mutation

Incidental Mutation 'R5184:Aph1a'

397735

Institutional Source

Beutler Lab

Gene Symbol

Aph1a

Ensembl Gene

ENSMUSG00000015750

Gene Name

aph1 homolog A, gamma secretase subunit

Synonyms

6530402N02Rik

MMRRC Submission

042763-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R5184 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

95801281-95805600 bp(+) (GRCm39)

Type of Mutation

splice site (2029 bp from exon)

DNA Base Change (assembly)

T to A at 95803051 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000036983 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000015894] [ENSMUST00000036181] [ENSMUST00000036360] [ENSMUST00000056710] [ENSMUST00000090476] [ENSMUST00000171519] [ENSMUST00000147962] [ENSMUST00000197081]

AlphaFold

Q8BVF7

PDB Structure

Crystal Structure of the Extracellular Domain of Murine Carbonic Anhydrase XIV [X-RAY DIFFRACTION]
Crystal Structure of the Extracellular Domain of Murine Carbonic Anhydrase XIV in Complex with Acetazolamide [X-RAY DIFFRACTION]

Predicted Effect

possibly damaging
Transcript: ENSMUST00000015894
AA Change: I168N

PolyPhen 2 Score 0.937 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000015894
Gene: ENSMUSG00000015750
AA Change: I168N

Domain	Start	End	E-Value	Type
Pfam:Aph-1	2	246	7.3e-98	PFAM

Predicted Effect

probably null
Transcript: ENSMUST00000036181

SMART Domains

Protein: ENSMUSP00000036983
Gene: ENSMUSG00000038526

Domain	Start	End	E-Value	Type
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

Domain	Start	End	E-Value	Type
Pfam:DUF4634	1	145	3.6e-64	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000056710
AA Change: I168N

PolyPhen 2 Score 0.937 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000058846
Gene: ENSMUSG00000015750
AA Change: I168N

Domain	Start	End	E-Value	Type
Pfam:Aph-1	2	239	1.2e-96	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000090476

SMART Domains

Protein: ENSMUSP00000102749
Gene: ENSMUSG00000038543

Domain	Start	End	E-Value	Type
Pfam:DUF4634	1	146	1.8e-65	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000133611

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000145949

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000197232

Predicted Effect

probably benign
Transcript: ENSMUST00000171519

SMART Domains

Protein: ENSMUSP00000127666
Gene: ENSMUSG00000038543

Domain	Start	End	E-Value	Type
Pfam:DUF4634	1	146	1.5e-65	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000147962

SMART Domains

Protein: ENSMUSP00000117464
Gene: ENSMUSG00000038526

Domain	Start	End	E-Value	Type
Carb_anhydrase	8	171	1.79e-39	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000197081

Meta Mutation Damage Score

0.5728

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.1%
20x: 94.6%

Validation Efficiency

98% (63/64)

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: 59 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Arid3a	A	G	10: 79,786,603 (GRCm39)	E452G	possibly damaging	Het
Barhl2	A	G	5: 106,605,506 (GRCm39)	S68P	unknown	Het
Carf	T	C	1: 60,147,333 (GRCm39)	S17P	probably damaging	Het
Ccdc90b	A	G	7: 92,224,019 (GRCm39)	D145G	probably damaging	Het
Cyp7a1	A	T	4: 6,271,207 (GRCm39)	N316K	probably benign	Het
Daam2	A	G	17: 49,801,419 (GRCm39)	I106T	possibly damaging	Het
Dmtf1	A	G	5: 9,176,641 (GRCm39)	V437A	probably benign	Het
E2f2	A	T	4: 135,911,751 (GRCm39)	Y254F	possibly damaging	Het
Ehmt1	G	T	2: 24,767,509 (GRCm39)	P135T	probably damaging	Het
Ern2	T	C	7: 121,779,182 (GRCm39)	T221A	probably benign	Het
Fam227b	G	A	2: 125,958,043 (GRCm39)	P241S	probably damaging	Het
Fermt1	A	G	2: 132,783,883 (GRCm39)	V42A	possibly damaging	Het
Fgf3	A	G	7: 144,396,547 (GRCm39)	D187G	probably damaging	Het
Flnb	T	A	14: 7,901,945 (GRCm38)	V936E	probably damaging	Het
Herc2	T	C	7: 55,772,099 (GRCm39)	Y1093H	probably damaging	Het
Invs	A	G	4: 48,283,242 (GRCm39)		probably benign	Het
Katnb1	T	A	8: 95,824,608 (GRCm39)	I534N	possibly damaging	Het
Kcnq5	A	T	1: 21,472,711 (GRCm39)	D826E	probably damaging	Het
Klra9	A	T	6: 130,165,675 (GRCm39)	N113K	probably benign	Het
Knl1	A	G	2: 118,899,657 (GRCm39)	K453E	probably damaging	Het
Lgi4	C	T	7: 30,770,182 (GRCm39)		probably benign	Het
Lpin3	A	G	2: 160,739,058 (GRCm39)	S289G	probably benign	Het
Mapre1	T	A	2: 153,599,987 (GRCm39)	V137E	possibly damaging	Het
Mark4	A	G	7: 19,181,168 (GRCm39)	F144L	possibly damaging	Het
Mogat2	G	T	7: 98,872,842 (GRCm39)	A114E	possibly damaging	Het
Msh2	C	A	17: 88,030,841 (GRCm39)	A906E	probably benign	Het
Nell2	A	G	15: 95,425,690 (GRCm39)	L19P	possibly damaging	Het
Nfia	A	T	4: 97,671,585 (GRCm39)	K98N	probably damaging	Het
Nutm1	T	A	2: 112,079,345 (GRCm39)	T857S	possibly damaging	Het
Or14a257	TG	T	7: 86,138,499 (GRCm39)		probably null	Het
Or52a5	T	C	7: 103,426,611 (GRCm39)	K314E	probably benign	Het
Or8g17	T	A	9: 38,929,998 (GRCm39)	I280F	probably damaging	Het
Pde10a	T	C	17: 9,195,987 (GRCm39)	L706P	probably damaging	Het
Penk	A	G	4: 4,134,296 (GRCm39)	L117P	probably damaging	Het
Pgap1	A	G	1: 54,521,015 (GRCm39)	S876P	probably damaging	Het
Pmfbp1	T	C	8: 110,254,399 (GRCm39)	I478T	possibly damaging	Het
Pole	G	A	5: 110,442,800 (GRCm39)	E318K	possibly damaging	Het
Prr12	C	A	7: 44,695,801 (GRCm39)	V1222L	unknown	Het
Prune2	T	C	19: 17,193,721 (GRCm39)	S3070P	possibly damaging	Het
Rnf19a	A	G	15: 36,244,342 (GRCm39)	C573R	probably benign	Het
Rp1l1	T	C	14: 64,267,629 (GRCm39)	S1072P	probably damaging	Het
Rskr	T	C	11: 78,183,573 (GRCm39)	F194L	probably benign	Het
Semp2l1	A	T	1: 32,584,729 (GRCm39)	C394S	probably damaging	Het
Sh3pxd2a	T	C	19: 47,261,850 (GRCm39)	N315S	possibly damaging	Het
Snph	T	C	2: 151,436,464 (GRCm39)	I86V	probably damaging	Het
Sox6	A	G	7: 115,376,463 (GRCm39)	Y90H	probably damaging	Het
Tbc1d13	T	A	2: 30,032,323 (GRCm39)	C145S	probably benign	Het
Tcp11l1	T	C	2: 104,530,289 (GRCm39)	E65G	probably damaging	Het
Thrb	G	T	14: 18,011,181 (GRCm38)	E186*	probably null	Het
Tmem101	A	G	11: 102,047,059 (GRCm39)	Y38H	possibly damaging	Het
Trarg1	T	A	11: 76,571,134 (GRCm39)	L50Q	probably damaging	Het
Urb1	A	T	16: 90,580,162 (GRCm39)		probably null	Het
Usp10	G	A	8: 120,683,420 (GRCm39)	V764I	possibly damaging	Het
Usp25	A	G	16: 76,906,115 (GRCm39)	E857G	probably benign	Het
Vmn1r17	A	G	6: 57,337,828 (GRCm39)	V130A	probably benign	Het
Wdr35	T	C	12: 9,068,142 (GRCm39)	L775P	probably damaging	Het
Xpnpep1	T	C	19: 53,001,845 (GRCm39)	T134A	probably benign	Het
Zbtb10	T	C	3: 9,329,731 (GRCm39)	V363A	probably damaging	Het
Zfp108	G	T	7: 23,960,163 (GRCm39)	K251N	probably benign	Het

Other mutations in Aph1a

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH 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
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
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'- CAGGTAAGGCCCACTTCTAACC -3'
(R):5'- AGAAGTCAAGATTCTGCCTCCG -3'

Sequencing Primer
(F):5'- AAGGCCCACTTCTAACCTTGCC -3'
(R):5'- GGTGACTTACTAGGTGGGAAC -3'

Posted On

2016-07-06