Mutagenetix > Incidental Mutation

Incidental Mutation 'R1754:Aire'

193859

Institutional Source

Beutler Lab

Gene Symbol

Aire

Ensembl Gene

ENSMUSG00000000731

Gene Name

autoimmune regulator (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy)

Synonyms

MMRRC Submission

039786-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R1754 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

78030022-78043610 bp(-) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 78030290 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Glutamine to Leucine at position 533 (Q533L)

Ref Sequence

ENSEMBL: ENSMUSP00000122659 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000019257] [ENSMUST00000105395] [ENSMUST00000105396] [ENSMUST00000128241] [ENSMUST00000130972] [ENSMUST00000131028] [ENSMUST00000140636] [ENSMUST00000143735] [ENSMUST00000145975] [ENSMUST00000148469] [ENSMUST00000154374] [ENSMUST00000155021] [ENSMUST00000156417]

AlphaFold

Q9Z0E3

Predicted Effect

probably damaging
Transcript: ENSMUST00000019257
AA Change: Q537L

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000019257
Gene: ENSMUSG00000000731
AA Change: Q537L

Domain	Start	End	E-Value	Type
Pfam:Sp100	1	107	8.9e-34	PFAM
SAND	198	264	2.61e-26	SMART
PHD	299	342	6.75e-11	SMART
RING	300	341	3.63e0	SMART
low complexity region	398	419	N/A	INTRINSIC
PHD	432	475	7.82e-7	SMART
RING	433	474	2.49e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000105395

SMART Domains

Protein: ENSMUSP00000101034
Gene: ENSMUSG00000000731

Domain	Start	End	E-Value	Type
Pfam:Sp100	1	107	1.6e-34	PFAM
SAND	198	264	2.61e-26	SMART
PHD	300	343	6.75e-11	SMART

Predicted Effect

possibly damaging
Transcript: ENSMUST00000105396
AA Change: Q478L

PolyPhen 2 Score 0.462 (Sensitivity: 0.89; Specificity: 0.90)

SMART Domains

Protein: ENSMUSP00000101035
Gene: ENSMUSG00000000731
AA Change: Q478L

Domain	Start	End	E-Value	Type
Pfam:Sp100	1	107	2.2e-34	PFAM
SAND	198	264	2.61e-26	SMART
PHD	299	342	6.75e-11	SMART
RING	300	341	3.63e0	SMART
PHD	373	416	7.82e-7	SMART
RING	374	415	2.49e0	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000128241
AA Change: Q538L

PolyPhen 2 Score 0.994 (Sensitivity: 0.69; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000114904
Gene: ENSMUSG00000000731
AA Change: Q538L

Domain	Start	End	E-Value	Type
Pfam:Sp100	5	104	3.3e-27	PFAM
SAND	198	264	2.61e-26	SMART
PHD	300	343	6.75e-11	SMART
RING	301	342	3.63e0	SMART
low complexity region	399	420	N/A	INTRINSIC
PHD	433	476	7.82e-7	SMART
RING	434	475	2.49e0	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000130972
AA Change: Q533L

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

SMART Domains

Protein: ENSMUSP00000122659
Gene: ENSMUSG00000000731
AA Change: Q533L

Domain	Start	End	E-Value	Type
Pfam:Sp100	1	107	2.6e-34	PFAM
SAND	198	264	2.61e-26	SMART
PHD	295	338	6.75e-11	SMART
RING	296	337	3.63e0	SMART
low complexity region	394	415	N/A	INTRINSIC
PHD	428	471	7.82e-7	SMART
RING	429	470	2.49e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000131028

SMART Domains

Protein: ENSMUSP00000114808
Gene: ENSMUSG00000000731

Domain	Start	End	E-Value	Type
Pfam:Sp100	5	57	2.6e-13	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000140636

SMART Domains

Protein: ENSMUSP00000121477
Gene: ENSMUSG00000000731

Domain	Start	End	E-Value	Type
Pfam:Sp100	1	107	1.6e-34	PFAM
SAND	198	264	2.61e-26	SMART
PHD	295	338	6.75e-11	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000143452

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000143548

Predicted Effect

probably benign
Transcript: ENSMUST00000143735

SMART Domains

Protein: ENSMUSP00000123678
Gene: ENSMUSG00000000731

Domain	Start	End	E-Value	Type
Pfam:Sp100	1	107	1.1e-34	PFAM
SAND	198	264	2.61e-26	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000145975
AA Change: Q534L

PolyPhen 2 Score 0.968 (Sensitivity: 0.77; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000120150
Gene: ENSMUSG00000000731
AA Change: Q534L

Domain	Start	End	E-Value	Type
Pfam:Sp100	1	107	2.6e-34	PFAM
SAND	198	264	2.61e-26	SMART
PHD	296	339	6.75e-11	SMART
RING	297	338	3.63e0	SMART
low complexity region	395	416	N/A	INTRINSIC
PHD	429	472	7.82e-7	SMART
RING	430	471	2.49e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000148469

SMART Domains

Protein: ENSMUSP00000118317
Gene: ENSMUSG00000000731

Domain	Start	End	E-Value	Type
Pfam:Sp100	1	107	1.6e-34	PFAM
SAND	198	264	2.61e-26	SMART
PHD	296	339	6.75e-11	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000154374
AA Change: Q479L

PolyPhen 2 Score 0.983 (Sensitivity: 0.75; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000117094
Gene: ENSMUSG00000000731
AA Change: Q479L

Domain	Start	End	E-Value	Type
Pfam:Sp100	1	107	7.4e-34	PFAM
SAND	198	264	2.61e-26	SMART
PHD	300	343	6.75e-11	SMART
RING	301	342	3.63e0	SMART
PHD	374	417	7.82e-7	SMART
RING	375	416	2.49e0	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000155021
AA Change: Q474L

PolyPhen 2 Score 0.992 (Sensitivity: 0.70; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000122190
Gene: ENSMUSG00000000731
AA Change: Q474L

Domain	Start	End	E-Value	Type
Pfam:Sp100	1	107	2.2e-34	PFAM
SAND	198	264	2.61e-26	SMART
PHD	295	338	6.75e-11	SMART
RING	296	337	3.63e0	SMART
PHD	369	412	7.82e-7	SMART
RING	370	411	2.49e0	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000156417

SMART Domains

Protein: ENSMUSP00000115162
Gene: ENSMUSG00000000731

Domain	Start	End	E-Value	Type
Pfam:Sp100	1	107	1.6e-34	PFAM
SAND	198	264	2.61e-26	SMART
PHD	299	342	6.75e-11	SMART

Coding Region Coverage

1x: 97.5%
3x: 97.0%
10x: 95.6%
20x: 93.3%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a transcriptional regulator that forms nuclear bodies and interacts with the transcriptional coactivator CREB binding protein. The encoded protein plays an important role in immunity by regulating the expression of autoantigens and negative selection of autoreactive T-cells in the thymus. Mutations in this gene cause the rare autosomal-recessive systemic autoimmune disease termed autoimmune polyendocrinopathy with candidiasis and ectodermal dystrophy (APECED). [provided by RefSeq, Jun 2012]
PHENOTYPE: Targeted mutations that inactivate the gene result in immune system dysfunction characterized by multiorgan lymphocytic infiltration and circulating autoantibodies. Whereas one line is fertile, another exhibits male and female sterility. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 87 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930563D23Rik	A	G	16: 92,321,031	V123A	probably damaging	Het
Abca2	T	A	2: 25,434,333	L234M	probably benign	Het
Abca3	G	A	17: 24,377,779	S402N	probably benign	Het
Acad12	A	T	5: 121,607,481	V249D	probably benign	Het
Acp4	T	C	7: 44,255,004	I212V	probably benign	Het
Actl6a	T	A	3: 32,718,574	V233D	probably damaging	Het
Aldh3b3	T	C	19: 3,968,517	S411P	probably benign	Het
Amer2	A	G	14: 60,379,757	K467R	probably damaging	Het
Apol9b	A	T	15: 77,735,762	I253F	probably benign	Het
Arid1b	A	G	17: 5,279,201		probably null	Het
Atp6v0a4	T	C	6: 38,067,829	T494A	probably benign	Het
Atp6v1b2	A	G	8: 69,101,961	D106G	probably benign	Het
Avpr1b	T	C	1: 131,600,101	S121P	probably damaging	Het
Bcl11a	A	C	11: 24,164,724	E689A	probably damaging	Het
Brpf3	T	G	17: 28,821,323	L906R	probably benign	Het
Btn1a1	T	C	13: 23,460,468	K287E	probably benign	Het
Cacna1i	A	G	15: 80,371,529	H871R	probably damaging	Het
Cd14	A	T	18: 36,725,514	L296Q	probably damaging	Het
Col1a2	G	A	6: 4,518,822		probably benign	Het
Colgalt1	G	T	8: 71,623,179	W490L	probably damaging	Het
Ctnna2	A	G	6: 77,636,749	I273T	possibly damaging	Het
Dnah7a	A	T	1: 53,504,185	D2275E	probably benign	Het
Dnah7a	A	C	1: 53,561,900		probably null	Het
Egfem1	T	C	3: 29,668,333	Y404H	possibly damaging	Het
Esm1	A	T	13: 113,216,696	N171Y	probably damaging	Het
Exoc1	T	G	5: 76,560,322		probably null	Het
Fcho1	A	G	8: 71,711,246	I580T	probably benign	Het
Fgfr1	A	G	8: 25,570,210	H552R	probably damaging	Het
Fsbp	A	G	4: 11,583,906	R202G	probably damaging	Het
Gabra6	A	G	11: 42,316,561	V231A	probably damaging	Het
Gm8765	A	T	13: 50,701,087	T254S	probably damaging	Het
Gmeb1	A	G	4: 132,232,027	S239P	probably benign	Het
Gnpat	T	A	8: 124,877,006	Y208N	probably damaging	Het
Il21	T	C	3: 37,225,525	K114R	possibly damaging	Het
Inhbc	T	C	10: 127,370,293	D35G	possibly damaging	Het
Inpp4b	A	T	8: 81,770,811	T87S	probably damaging	Het
Kcns2	T	C	15: 34,839,517	I342T	possibly damaging	Het
Ky	A	T	9: 102,541,927	T378S	possibly damaging	Het
Lcat	CAT	C	8: 105,941,814		probably null	Het
Lrrc8d	T	C	5: 105,812,657	V311A	probably benign	Het
Mief1	A	G	15: 80,249,602	I287V	probably damaging	Het
Mrpl47	A	G	3: 32,730,084	V179A	probably benign	Het
Mtcl1	T	C	17: 66,380,183	K576R	probably damaging	Het
Myh10	C	A	11: 68,813,058	A1902E	probably damaging	Het
Nlrp3	A	G	11: 59,558,402	T837A	possibly damaging	Het
Nr1i3	T	C	1: 171,217,394	Y132H	probably damaging	Het
Oit3	T	C	10: 59,427,940		probably null	Het
Olfr1186	A	T	2: 88,525,815	R77S	probably damaging	Het
Olfr1467	T	C	19: 13,365,353	S242P	probably damaging	Het
Olfr193	T	A	16: 59,110,581	I10F	probably benign	Het
Olfr30	A	T	11: 58,455,262	M229K	probably damaging	Het
Olfr427	A	G	1: 174,100,033	T192A	probably benign	Het
Olfr533	A	T	7: 140,466,860	I220F	probably damaging	Het
Olfr8	T	A	10: 78,955,697	V164E	probably damaging	Het
Olfr825	G	A	10: 130,163,164	T54I	probably benign	Het
Pdlim4	T	C	11: 54,055,873	E196G	possibly damaging	Het
Pigs	A	G	11: 78,337,847	Y293C	probably damaging	Het
Pkd1l2	A	T	8: 117,030,719	S1527T	possibly damaging	Het
Pkd2l1	A	T	19: 44,155,601	Y344*	probably null	Het
Pmp2	T	C	3: 10,182,224		probably null	Het
Polr3e	T	C	7: 120,939,298		probably null	Het
Ppp3ca	C	G	3: 136,881,448	I230M	probably benign	Het
Ppp5c	T	C	7: 17,005,310	H463R	probably benign	Het
Ptger1	A	G	8: 83,669,297	N328D	probably benign	Het
Rhno1	A	T	6: 128,357,859	I167N	probably benign	Het
Rictor	C	A	15: 6,735,368	P34H	probably damaging	Het
Rnf10	A	C	5: 115,245,865	S630R	probably damaging	Het
Rnf168	A	G	16: 32,299,124	Q501R	probably benign	Het
Rngtt	T	G	4: 33,329,634		probably null	Het
Samd9l	G	T	6: 3,373,126	F1378L	probably damaging	Het
Slc9c1	T	A	16: 45,589,509	M864K	probably benign	Het
Slitrk5	T	C	14: 111,680,519	F525S	probably damaging	Het
Sox6	T	C	7: 115,477,055	M784V	probably benign	Het
Spint2	C	T	7: 29,260,366		probably null	Het
Ssh1	A	T	5: 113,955,845	I276N	probably damaging	Het
Trank1	T	A	9: 111,392,871	V2892D	probably benign	Het
Ttn	C	A	2: 76,751,040	E21424*	probably null	Het
Usp17lc	T	C	7: 103,418,848	I450T	probably benign	Het
Vcan	A	G	13: 89,704,735	V702A	probably benign	Het
Vmn1r36	TA	TAA	6: 66,716,533		probably null	Het
Vmn2r51	G	T	7: 10,099,946	D388E	probably benign	Het
Zfp106	G	A	2: 120,533,763	S721L	probably damaging	Het
Zfp106	A	C	2: 120,533,764	S721A	probably damaging	Het
Zfp189	T	A	4: 49,529,342	H148Q	possibly damaging	Het
Zfp352	A	T	4: 90,223,809	Y62F	probably benign	Het
Zfp839	T	C	12: 110,855,457	V235A	probably damaging	Het
Zfp871	T	C	17: 32,775,334	Y289C	probably damaging	Het

Other mutations in Aire

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01744:Aire	APN	10	78036723	nonsense	probably null
IGL01969:Aire	APN	10	78042982	missense	probably damaging	1.00
Million	UTSW	10	78037975	missense	probably damaging	1.00
BB008:Aire	UTSW	10	78030296	missense	probably damaging	1.00
BB018:Aire	UTSW	10	78030296	missense	probably damaging	1.00
E0370:Aire	UTSW	10	78042063	missense	probably damaging	1.00
IGL03055:Aire	UTSW	10	78043069	missense	probably damaging	1.00
R0326:Aire	UTSW	10	78042599	missense	probably damaging	1.00
R0675:Aire	UTSW	10	78034493	splice site	probably benign
R1748:Aire	UTSW	10	78043480	missense	probably damaging	0.99
R2014:Aire	UTSW	10	78042958	missense	probably damaging	1.00
R2015:Aire	UTSW	10	78042958	missense	probably damaging	1.00
R3800:Aire	UTSW	10	78042055	splice site	probably null
R5424:Aire	UTSW	10	78036719	missense	probably damaging	1.00
R5517:Aire	UTSW	10	78039691	missense	probably benign	0.14
R5983:Aire	UTSW	10	78043069	missense	probably damaging	1.00
R6135:Aire	UTSW	10	78042967	missense	probably damaging	1.00
R6856:Aire	UTSW	10	78030255	missense	probably damaging	1.00
R7405:Aire	UTSW	10	78034613	missense	probably benign	0.01
R7484:Aire	UTSW	10	78042570	missense	probably damaging	1.00
R7606:Aire	UTSW	10	78037933	missense	probably damaging	1.00
R7931:Aire	UTSW	10	78030296	missense	probably damaging	1.00
R8867:Aire	UTSW	10	78037975	missense	probably damaging	1.00
R8887:Aire	UTSW	10	78034464	missense	probably damaging	0.96
R9115:Aire	UTSW	10	78043475	missense
R9562:Aire	UTSW	10	78035745	missense	probably benign
R9623:Aire	UTSW	10	78037975	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- CTCTACAAAGATCAGGGCCATCTGC -3'
(R):5'- ACTGGATCAAGAGACCTCCCTTCAC -3'

Sequencing Primer
(F):5'- ATCTGCAAGCTGAGTCCAG -3'
(R):5'- TGTCAAGATGGCTCTATGGAGG -3'

Posted On

2014-05-23