Mutagenetix > Incidental Mutation

Incidental Mutation 'R1735:Aph1a'

199619

Institutional Source

Beutler Lab

Gene Symbol

Aph1a

Ensembl Gene

ENSMUSG00000015750

Gene Name

aph1 homolog A, gamma secretase subunit

Synonyms

6530402N02Rik

MMRRC Submission

039767-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R1735 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

95801281-95805600 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 95802821 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glutamic Acid at position 140 (D140E)

Ref Sequence

ENSEMBL: ENSMUSP00000058846 (fasta)

Gene Model

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

AlphaFold

Q8BVF7

Predicted Effect

probably damaging
Transcript: ENSMUST00000015894
AA Change: D140E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000015894
Gene: ENSMUSG00000015750
AA Change: D140E

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

Predicted Effect

probably benign
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

probably damaging
Transcript: ENSMUST00000056710
AA Change: D140E

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000058846
Gene: ENSMUSG00000015750
AA Change: D140E

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

Coding Region Coverage

1x: 97.6%
3x: 97.0%
10x: 95.3%
20x: 92.1%

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: 77 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acot5	A	T	12: 84,122,261 (GRCm39)	I282F	probably benign	Het
Adam19	C	A	11: 46,029,744 (GRCm39)	Q730K	probably benign	Het
Adgrv1	A	G	13: 81,636,066 (GRCm39)	V3481A	possibly damaging	Het
Akr1c20	T	C	13: 4,537,207 (GRCm39)	D316G	probably benign	Het
Ap3b1	G	A	13: 94,630,225 (GRCm39)	V827I	unknown	Het
Arhgef19	G	T	4: 140,976,929 (GRCm39)	V502L	possibly damaging	Het
Arl9	T	C	5: 77,154,473 (GRCm39)	F67S	probably damaging	Het
B430305J03Rik	G	A	3: 61,271,361 (GRCm39)		probably benign	Het
B4galnt2	A	G	11: 95,781,809 (GRCm39)	F119L	probably damaging	Het
Bcap29	T	A	12: 31,680,839 (GRCm39)	N49I	probably damaging	Het
Capn11	T	A	17: 45,943,327 (GRCm39)	K616*	probably null	Het
Cdh12	T	A	15: 21,520,452 (GRCm39)	Y306N	probably damaging	Het
Cep350	T	A	1: 155,828,960 (GRCm39)	N315Y	probably damaging	Het
Cfap300	A	C	9: 8,027,266 (GRCm39)	S91A	probably benign	Het
Cited2	C	A	10: 17,599,794 (GRCm39)	P34Q	probably damaging	Het
Cmya5	A	T	13: 93,226,297 (GRCm39)	D2930E	probably benign	Het
Cog3	T	A	14: 75,966,761 (GRCm39)	K470*	probably null	Het
Commd10	A	G	18: 47,123,552 (GRCm39)	T136A	probably benign	Het
Csf2ra	C	A	19: 61,214,782 (GRCm39)	D181Y	probably damaging	Het
Csmd1	T	A	8: 15,982,610 (GRCm39)	I2686F	probably damaging	Het
Dhx29	T	C	13: 113,081,620 (GRCm39)	S415P	probably benign	Het
Dsel	A	T	1: 111,788,645 (GRCm39)	F630Y	probably damaging	Het
Ell	T	A	8: 71,031,590 (GRCm39)	I96N	possibly damaging	Het
Ephx2	T	A	14: 66,325,752 (GRCm39)	I358L	probably benign	Het
Fam162b	A	G	10: 51,463,307 (GRCm39)	I120T	probably damaging	Het
Fam187a	T	C	11: 102,776,606 (GRCm39)	Y137H	probably damaging	Het
Fastk	T	C	5: 24,646,801 (GRCm39)	E403G	probably damaging	Het
Fcrlb	C	A	1: 170,734,901 (GRCm39)	V409F	probably benign	Het
Flot2	G	T	11: 77,948,831 (GRCm39)	A269S	probably benign	Het
Gpd2	T	A	2: 57,245,563 (GRCm39)	N419K	probably damaging	Het
Hecw1	A	T	13: 14,552,350 (GRCm39)	M61K	probably null	Het
Htr2a	T	C	14: 74,943,568 (GRCm39)	F383L	probably damaging	Het
Kctd6	C	T	14: 8,222,253 (GRCm38)	R32C	probably damaging	Het
Khdc1a	A	G	1: 21,421,189 (GRCm39)	T125A	probably benign	Het
Klhl40	T	C	9: 121,609,004 (GRCm39)	S390P	probably benign	Het
Lonp1	G	A	17: 56,921,956 (GRCm39)	T808I	probably damaging	Het
Loxhd1	A	C	18: 77,492,585 (GRCm39)	D1342A	probably damaging	Het
Lrat	T	C	3: 82,804,417 (GRCm39)	I187V	probably benign	Het
Lrif1	T	C	3: 106,643,162 (GRCm39)	*238Q	probably null	Het
Lrp2bp	T	C	8: 46,465,025 (GRCm39)	F48S	probably benign	Het
Mafg	A	G	11: 120,520,504 (GRCm39)	M32T	possibly damaging	Het
Map4	C	T	9: 109,864,023 (GRCm39)	T416I	probably benign	Het
N4bp2	T	C	5: 65,965,659 (GRCm39)	F1236S	probably damaging	Het
Nfatc3	A	G	8: 106,810,466 (GRCm39)	D414G	probably damaging	Het
Nhsl3	G	T	4: 129,117,370 (GRCm39)	S476R	probably damaging	Het
Nrip2	T	G	6: 128,382,037 (GRCm39)	V50G	probably damaging	Het
Or10aa3	A	T	1: 173,878,365 (GRCm39)	K142I	probably benign	Het
Or10j5	A	G	1: 172,784,374 (GRCm39)	N4S	probably benign	Het
Or52ae7	T	A	7: 103,119,353 (GRCm39)	F36I	possibly damaging	Het
Or5b24	T	A	19: 12,912,207 (GRCm39)	I35N	probably damaging	Het
Pcdhb18	A	T	18: 37,623,822 (GRCm39)	H384L	probably benign	Het
Pik3r1	A	T	13: 101,822,882 (GRCm39)	Y607N	probably damaging	Het
Plagl2	G	A	2: 153,074,397 (GRCm39)	T168I	probably damaging	Het
Polr2a	A	G	11: 69,633,222 (GRCm39)	S912P	probably damaging	Het
Ppp1r16b	A	G	2: 158,603,415 (GRCm39)	K447E	possibly damaging	Het
Prkd1	T	C	12: 50,388,822 (GRCm39)	E907G	possibly damaging	Het
Rabep2	A	G	7: 126,043,712 (GRCm39)	R470G	probably damaging	Het
Rasal2	T	C	1: 157,001,730 (GRCm39)	Y518C	probably damaging	Het
Rbmxl1	A	G	8: 79,232,711 (GRCm39)	Y211H	probably damaging	Het
Rdh7	T	C	10: 127,720,454 (GRCm39)	Y306C	probably benign	Het
Rtn3	T	C	19: 7,435,276 (GRCm39)	I220V	probably damaging	Het
Scn8a	A	G	15: 100,913,742 (GRCm39)	N1045D	possibly damaging	Het
Scube1	T	C	15: 83,491,638 (GRCm39)	H952R	probably damaging	Het
Sf3b1	A	G	1: 55,039,811 (GRCm39)	I690T	probably damaging	Het
Sharpin	T	C	15: 76,232,136 (GRCm39)	K240R	probably benign	Het
Skint5	A	G	4: 113,420,656 (GRCm39)	I1108T	unknown	Het
Snip1	A	G	4: 124,964,994 (GRCm39)	D133G	probably benign	Het
St3gal3	T	C	4: 117,871,971 (GRCm39)	Y77C	probably damaging	Het
Sytl3	T	C	17: 6,982,880 (GRCm39)	V112A	probably benign	Het
Tnxb	C	T	17: 34,936,944 (GRCm39)	P3718S	probably damaging	Het
Ttc24	A	T	3: 87,980,401 (GRCm39)		probably null	Het
Ubr3	A	T	2: 69,839,473 (GRCm39)	E1529V	probably damaging	Het
Utrn	T	A	10: 12,585,882 (GRCm39)	H965L	probably benign	Het
Xrn2	T	A	2: 146,903,343 (GRCm39)	L781Q	probably damaging	Het
Zbtb11	T	C	16: 55,811,045 (GRCm39)	I401T	probably benign	Het
Zc3h14	C	T	12: 98,724,839 (GRCm39)	P167L	probably damaging	Het
Zfp609	G	T	9: 65,610,374 (GRCm39)	S863*	probably null	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
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
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'- CATACTTGACTTCCAAGGAGAGGCG -3'
(R):5'- TCAGAAGGTGACTCCCAACTACCAG -3'

Sequencing Primer
(F):5'- CCAAGGAGAGGCGGTCTG -3'
(R):5'- TGCTGTCAGAAAGGCTGC -3'

Posted On

2014-05-23