Mutagenetix > Incidental Mutation

Incidental Mutation 'R8887:Aire'

677414

Institutional Source

Beutler Lab

Gene Symbol

Aire

Ensembl Gene

ENSMUSG00000000731

Gene Name

autoimmune regulator

Synonyms

MMRRC Submission

068752-MU

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

R8887 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

77865856-77879444 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 77870298 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Proline at position 476 (S476P)

Ref Sequence

ENSEMBL: ENSMUSP00000114904 (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: S475P

PolyPhen 2 Score 0.989 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000019257
Gene: ENSMUSG00000000731
AA Change: S475P

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
AA Change: L376P

PolyPhen 2 Score 0.074 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000101034
Gene: ENSMUSG00000000731
AA Change: L376P

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: S416P

PolyPhen 2 Score 0.827 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000101035
Gene: ENSMUSG00000000731
AA Change: S416P

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: S476P

PolyPhen 2 Score 0.960 (Sensitivity: 0.78; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000114904
Gene: ENSMUSG00000000731
AA Change: S476P

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: S471P

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000122659
Gene: ENSMUSG00000000731
AA Change: S471P

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
AA Change: L371P

PolyPhen 2 Score 0.074 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000121477
Gene: ENSMUSG00000000731
AA Change: L371P

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

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: S472P

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

SMART Domains

Protein: ENSMUSP00000120150
Gene: ENSMUSG00000000731
AA Change: S472P

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
AA Change: L372P

PolyPhen 2 Score 0.074 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000118317
Gene: ENSMUSG00000000731
AA Change: L372P

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: S417P

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000117094
Gene: ENSMUSG00000000731
AA Change: S417P

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: S412P

PolyPhen 2 Score 0.987 (Sensitivity: 0.73; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000122190
Gene: ENSMUSG00000000731
AA Change: S412P

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
AA Change: L375P

PolyPhen 2 Score 0.074 (Sensitivity: 0.93; Specificity: 0.85)

SMART Domains

Protein: ENSMUSP00000115162
Gene: ENSMUSG00000000731
AA Change: L375P

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: 100.0%
3x: 99.9%
10x: 99.5%
20x: 98.5%

Validation Efficiency

98% (93/95)

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: 97 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Acsbg2	T	C	17: 57,175,285 (GRCm39)	T76A	probably benign	Het
Actn1	A	G	12: 80,215,197 (GRCm39)	C860R	probably damaging	Het
Adam23	T	A	1: 63,554,744 (GRCm39)	L170Q	probably damaging	Het
Afdn	C	T	17: 14,116,401 (GRCm39)	R1620*	probably null	Het
Agfg1	A	G	1: 82,848,525 (GRCm39)		probably benign	Het
Arhgef26	A	G	3: 62,247,401 (GRCm39)	T162A	probably benign	Het
Atp1a2	T	C	1: 172,113,222 (GRCm39)	Q487R	probably null	Het
BC048507	T	A	13: 68,011,628 (GRCm39)	C2S	probably benign	Het
Bltp1	G	T	3: 37,087,503 (GRCm39)	A615S	possibly damaging	Het
Bnc2	A	C	4: 84,209,707 (GRCm39)		probably benign	Het
Bop1	C	T	15: 76,338,524 (GRCm39)	G473R	probably damaging	Het
C1galt1	A	G	6: 7,866,379 (GRCm39)	E75G	probably benign	Het
Cacna1i	T	C	15: 80,258,894 (GRCm39)	V1201A	possibly damaging	Het
Cecr2	C	A	6: 120,715,162 (GRCm39)	T249K	probably damaging	Het
Clca3a2	C	A	3: 144,790,810 (GRCm39)	G421*	probably null	Het
Clec1b	A	T	6: 129,378,703 (GRCm39)		probably null	Het
Cnksr3	C	T	10: 7,104,467 (GRCm39)	D79N	probably damaging	Het
Col15a1	A	G	4: 47,287,091 (GRCm39)	Q843R	probably damaging	Het
Col6a3	T	C	1: 90,755,948 (GRCm39)	S114G	probably benign	Het
Corin	A	T	5: 72,486,953 (GRCm39)		probably null	Het
Cyp2u1	A	G	3: 131,096,503 (GRCm39)	Y92H	probably damaging	Het
Dcbld2	T	C	16: 58,229,270 (GRCm39)	L51P	probably damaging	Het
Dip2c	T	A	13: 9,673,989 (GRCm39)		probably benign	Het
Dlc1	A	T	8: 37,051,481 (GRCm39)	V299E	probably benign	Het
Dlgap2	G	A	8: 14,229,682 (GRCm39)		probably null	Het
Dnah1	A	G	14: 31,032,997 (GRCm39)	L346P	probably damaging	Het
Dnah9	T	C	11: 65,746,210 (GRCm39)	T3968A	probably benign	Het
Duox2	A	C	2: 122,120,044 (GRCm39)	M822R	probably null	Het
E2f7	A	T	10: 110,610,674 (GRCm39)	Q433L	probably benign	Het
Eif3k	A	C	7: 28,679,901 (GRCm39)	Y42*	probably null	Het
Elmod3	A	G	6: 72,563,494 (GRCm39)	S45P	probably damaging	Het
Emilin3	C	A	2: 160,751,108 (GRCm39)	V214F	possibly damaging	Het
Fbxo10	A	T	4: 45,058,887 (GRCm39)	F283L	probably benign	Het
Fbxw7	T	C	3: 84,876,549 (GRCm39)	Y358H		Het
G430095P16Rik	A	G	8: 85,453,043 (GRCm39)	N10S	unknown	Het
Gldc	A	G	19: 30,111,156 (GRCm39)	V540A	possibly damaging	Het
Gm3667	T	A	14: 18,271,553 (GRCm39)	E67D	probably benign	Het
Golga3	T	A	5: 110,353,626 (GRCm39)		probably benign	Het
H60c	T	C	10: 3,217,255 (GRCm39)	E38G	probably benign	Het
Hectd4	A	G	5: 121,433,541 (GRCm39)	D952G	probably benign	Het
Hoxb8	T	A	11: 96,175,223 (GRCm39)	L220Q	probably damaging	Het
Ice1	A	T	13: 70,751,050 (GRCm39)	L1679M	probably damaging	Het
Ifi202b	T	A	1: 173,802,480 (GRCm39)	Y118F	probably damaging	Het
Ift122	A	T	6: 115,868,880 (GRCm39)	T456S	probably benign	Het
Ighg3	G	A	12: 113,323,845 (GRCm39)	T181I		Het
Ighv1-66	C	A	12: 115,557,032 (GRCm39)	V17F	probably damaging	Het
Ighv5-12-4	A	G	12: 113,726,130 (GRCm39)	V31A	possibly damaging	Het
Ints12	T	A	3: 132,815,003 (GRCm39)	N403K	probably damaging	Het
Itpr3	G	A	17: 27,337,651 (GRCm39)		probably benign	Het
Kalrn	A	C	16: 34,047,496 (GRCm39)	N908K	probably benign	Het
Kctd9	G	A	14: 67,962,016 (GRCm39)	V20I	unknown	Het
Krt78	G	T	15: 101,861,746 (GRCm39)	L167M	probably damaging	Het
Ldb1	T	C	19: 46,023,294 (GRCm39)	E206G	probably damaging	Het
Lig1	A	G	7: 13,030,713 (GRCm39)	Y455C	probably damaging	Het
Ltbp1	T	G	17: 75,486,077 (GRCm39)	I34S	probably damaging	Het
Map2	T	C	1: 66,454,758 (GRCm39)	I1216T	possibly damaging	Het
Mex3c	T	C	18: 73,706,800 (GRCm39)	V229A	probably damaging	Het
Mfsd11	T	C	11: 116,745,526 (GRCm39)		probably null	Het
Mroh1	A	G	15: 76,331,474 (GRCm39)	T1233A	probably benign	Het
Myct1	C	T	10: 5,554,208 (GRCm39)	T25I	probably damaging	Het
Nipbl	A	T	15: 8,391,271 (GRCm39)	H234Q	probably damaging	Het
Npc1l1	G	A	11: 6,175,665 (GRCm39)	P549S	probably damaging	Het
Or12d2	A	T	17: 37,624,642 (GRCm39)	L211Q	probably damaging	Het
Or4c3	A	G	2: 89,852,269 (GRCm39)	V47A	probably benign	Het
Or5h22	A	T	16: 58,894,846 (GRCm39)	V199D	possibly damaging	Het
Or5w22	A	G	2: 87,363,187 (GRCm39)	D270G	possibly damaging	Het
Or6c3b	A	T	10: 129,527,372 (GRCm39)	Y179*	probably null	Het
Padi3	A	T	4: 140,523,795 (GRCm39)	C228*	probably null	Het
Palld	T	A	8: 61,986,512 (GRCm39)	D1015V	unknown	Het
Pcna-ps2	A	T	19: 9,261,488 (GRCm39)	Y249F	probably benign	Het
Pelo	C	T	13: 115,225,451 (GRCm39)	C258Y	probably benign	Het
Ppp1r13b	A	T	12: 111,803,430 (GRCm39)		probably benign	Het
Pramel26	A	G	4: 143,539,257 (GRCm39)	F79L	probably damaging	Het
Prdm2	A	G	4: 142,860,771 (GRCm39)	W840R	probably damaging	Het
Prkcg	A	G	7: 3,370,857 (GRCm39)	D428G	possibly damaging	Het
Pus7	G	A	5: 23,948,476 (GRCm39)	R571*	probably null	Het
Rab11fip3	A	G	17: 26,286,927 (GRCm39)	C409R	possibly damaging	Het
Rdh13	T	C	7: 4,434,522 (GRCm39)	D186G	probably damaging	Het
Rslcan18	T	A	13: 67,246,793 (GRCm39)	H273L	probably damaging	Het
Rxfp1	T	A	3: 79,559,289 (GRCm39)		probably benign	Het
Sh3bp1	T	A	15: 78,788,540 (GRCm39)		probably null	Het
Siglecg	T	A	7: 43,058,008 (GRCm39)	S9T	probably benign	Het
Slc9a1	T	C	4: 133,139,258 (GRCm39)	F159L	probably benign	Het
Slc9a2	A	G	1: 40,758,009 (GRCm39)	I183V	probably benign	Het
St6galnac4	A	G	2: 32,484,110 (GRCm39)	M103V	probably damaging	Het
Tbc1d30	T	C	10: 121,187,059 (GRCm39)	D42G	possibly damaging	Het
Tlr5	C	A	1: 182,801,332 (GRCm39)	T212K	probably benign	Het
Trim43b	T	G	9: 88,969,642 (GRCm39)	I269L	probably benign	Het
Ttll6	T	C	11: 96,047,492 (GRCm39)	L697P	possibly damaging	Het
Ttn	T	G	2: 76,549,239 (GRCm39)	T31813P	probably damaging	Het
Ttn	A	T	2: 76,571,932 (GRCm39)	D26320E	probably damaging	Het
Uba6	A	G	5: 86,307,061 (GRCm39)		probably null	Het
Usp1	C	G	4: 98,819,185 (GRCm39)	Q216E	probably benign	Het
Vcan	T	C	13: 89,853,026 (GRCm39)	T645A	probably benign	Het
Wdr64	C	A	1: 175,599,850 (GRCm39)	P559H	probably benign	Het
Zfat	T	C	15: 68,056,315 (GRCm39)	Y247C	probably damaging	Het
Zfp979	A	T	4: 147,698,219 (GRCm39)	N163K	probably damaging	Het

Other mutations in Aire

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01744:Aire	APN	10	77,872,557 (GRCm39)	nonsense	probably null
IGL01969:Aire	APN	10	77,878,816 (GRCm39)	missense	probably damaging	1.00
Million	UTSW	10	77,873,809 (GRCm39)	missense	probably damaging	1.00
BB008:Aire	UTSW	10	77,866,130 (GRCm39)	missense	probably damaging	1.00
BB018:Aire	UTSW	10	77,866,130 (GRCm39)	missense	probably damaging	1.00
E0370:Aire	UTSW	10	77,877,897 (GRCm39)	missense	probably damaging	1.00
IGL03055:Aire	UTSW	10	77,878,903 (GRCm39)	missense	probably damaging	1.00
R0326:Aire	UTSW	10	77,878,433 (GRCm39)	missense	probably damaging	1.00
R0675:Aire	UTSW	10	77,870,327 (GRCm39)	splice site	probably benign
R1748:Aire	UTSW	10	77,879,314 (GRCm39)	missense	probably damaging	0.99
R1754:Aire	UTSW	10	77,866,124 (GRCm39)	missense	probably damaging	1.00
R2014:Aire	UTSW	10	77,878,792 (GRCm39)	missense	probably damaging	1.00
R2015:Aire	UTSW	10	77,878,792 (GRCm39)	missense	probably damaging	1.00
R3800:Aire	UTSW	10	77,877,889 (GRCm39)	splice site	probably null
R5424:Aire	UTSW	10	77,872,553 (GRCm39)	missense	probably damaging	1.00
R5517:Aire	UTSW	10	77,875,525 (GRCm39)	missense	probably benign	0.14
R5983:Aire	UTSW	10	77,878,903 (GRCm39)	missense	probably damaging	1.00
R6135:Aire	UTSW	10	77,878,801 (GRCm39)	missense	probably damaging	1.00
R6856:Aire	UTSW	10	77,866,089 (GRCm39)	missense	probably damaging	1.00
R7405:Aire	UTSW	10	77,870,447 (GRCm39)	missense	probably benign	0.01
R7484:Aire	UTSW	10	77,878,404 (GRCm39)	missense	probably damaging	1.00
R7606:Aire	UTSW	10	77,873,767 (GRCm39)	missense	probably damaging	1.00
R7931:Aire	UTSW	10	77,866,130 (GRCm39)	missense	probably damaging	1.00
R8867:Aire	UTSW	10	77,873,809 (GRCm39)	missense	probably damaging	1.00
R9115:Aire	UTSW	10	77,879,309 (GRCm39)	missense
R9562:Aire	UTSW	10	77,871,579 (GRCm39)	missense	probably benign
R9623:Aire	UTSW	10	77,873,809 (GRCm39)	missense	probably damaging	1.00

Predicted Primers

PCR Primer
(F):5'- AGCCAGAGATCTGTAGTACCTC -3'
(R):5'- GAGGTTTCCCAGTTAACCCG -3'

Sequencing Primer
(F):5'- GAGATCTGTAGTACCTCAACAAAAC -3'
(R):5'- TTCCCAGTTAACCCGGGCTG -3'

Posted On

2021-08-02