Mutagenetix > Incidental Mutation

Incidental Mutation 'R7232:Duoxa1'

562530

Institutional Source

Beutler Lab

Gene Symbol

Duoxa1

Ensembl Gene

ENSMUSG00000027224

Gene Name

dual oxidase maturation factor 1

Synonyms

Nip1

MMRRC Submission

045303-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R7232 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

122134012-122144255 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 122135728 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Isoleucine to Phenylalanine at position 124 (I124F)

Ref Sequence

ENSEMBL: ENSMUSP00000106166 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000028653] [ENSMUST00000028656] [ENSMUST00000110537] [ENSMUST00000110538] [ENSMUST00000147788] [ENSMUST00000148417] [ENSMUST00000154412]

AlphaFold

Q8VE49

Predicted Effect

probably damaging
Transcript: ENSMUST00000028653
AA Change: I124F

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

SMART Domains

Protein: ENSMUSP00000028653
Gene: ENSMUSG00000027224
AA Change: I124F

Domain	Start	End	E-Value	Type
Pfam:DuoxA	10	287	7.2e-115	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000028656

SMART Domains

Protein: ENSMUSP00000028656
Gene: ENSMUSG00000027225

Domain	Start	End	E-Value	Type
Pfam:DuoxA	10	286	5.5e-114	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000110537
AA Change: I124F

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

SMART Domains

Protein: ENSMUSP00000106166
Gene: ENSMUSG00000027224
AA Change: I124F

Domain	Start	End	E-Value	Type
Pfam:DuoxA	9	290	3.9e-128	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000110538
AA Change: I79F

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

SMART Domains

Protein: ENSMUSP00000106167
Gene: ENSMUSG00000027224
AA Change: I79F

Domain	Start	End	E-Value	Type
Pfam:DuoxA	9	70	1.7e-23	PFAM
Pfam:DuoxA	67	245	2.4e-80	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000147788
AA Change: I124F

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

SMART Domains

Protein: ENSMUSP00000116280
Gene: ENSMUSG00000027224
AA Change: I124F

Domain	Start	End	E-Value	Type
Pfam:DuoxA	9	134	5.9e-57	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000148417
AA Change: I124F

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

SMART Domains

Protein: ENSMUSP00000116963
Gene: ENSMUSG00000027224
AA Change: I124F

Domain	Start	End	E-Value	Type
Pfam:DuoxA	9	210	1.2e-99	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000154412

SMART Domains

Protein: ENSMUSP00000116911
Gene: ENSMUSG00000027224

Domain	Start	End	E-Value	Type
Pfam:DuoxA	9	100	6.3e-37	PFAM

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.7%

Validation Efficiency

99% (80/81)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Dual oxidases DUOX1 and DUOX2 are NADPH oxidases which are involved in hydrogen peroxide production necessary for thyroid hormonogenesis. They form a heterodimer with specific maturation factors DUOXA1 and DUOXA2, respectively, which is essential for the maturation and function of the DUOX enzyme complexes. This gene encodes the DUOX1 activator or maturation factor DUOXA1. Rat studies identified a bidirectional promoter which controls the transcription of the DUOX1 and DUOXA1 genes. This protein is cotransported to the cell surface when coexpressed with DUOX1 and is retained in the endoplasmic reticulum when expressed without DUOX1 protein. The expression of this gene or the DUOX1 gene is not suppressed by thyroglobulin (Tg), a macromolecular precursor in thyroid hormone synthesis, while the expression of the DUOX2 and DUOXA2 are significantly suppressed by the Tg. This protein is also a p53-regulated neurogenic factor involved in p53 dependent neuronal differentiation. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2013]
PHENOTYPE: Mice homozygous for a knock-out allele of Duoxa1 and 2 exhibit severe hypothyrodism with severe postnatal growth, delayed eye opening, enlarged thyroid, enlarged adenohypophysis, respiratory distress and death at weaning when weaned at 21 days. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 79 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930433I11Rik	G	A	7: 40,642,603 (GRCm39)	G91S	probably damaging	Het
Adam21	T	G	12: 81,607,330 (GRCm39)	N144T	probably damaging	Het
Adgrg7	T	C	16: 56,597,515 (GRCm39)		probably null	Het
Angpt4	T	C	2: 151,771,460 (GRCm39)	S259P	possibly damaging	Het
Aqr	A	C	2: 113,936,363 (GRCm39)	L1320R	probably damaging	Het
Arhgef10	G	A	8: 14,990,323 (GRCm39)	G266D	probably benign	Het
Bop1	A	G	15: 76,337,546 (GRCm39)	V693A	probably damaging	Het
Cd86	CA	CAA	16: 36,426,917 (GRCm39)		probably null	Het
Cdc5l	A	G	17: 45,738,863 (GRCm39)		probably null	Het
Cfap46	C	A	7: 139,197,493 (GRCm39)	R2126L	unknown	Het
Chek2	T	C	5: 111,008,781 (GRCm39)	V304A	probably damaging	Het
Cntnap4	T	A	8: 113,391,731 (GRCm39)		probably null	Het
Ctps1	C	A	4: 120,405,321 (GRCm39)	G374C	probably damaging	Het
Defa27	A	T	8: 21,805,625 (GRCm39)	I22F	probably damaging	Het
Dnah14	T	C	1: 181,584,928 (GRCm39)	S3220P	probably damaging	Het
Dop1b	T	G	16: 93,557,373 (GRCm39)		probably null	Het
Dpysl5	G	A	5: 30,949,642 (GRCm39)	V471I	probably benign	Het
Eif4enif1	A	G	11: 3,165,678 (GRCm39)	E85G	possibly damaging	Het
Eogt	T	A	6: 97,096,944 (GRCm39)	I355F	probably damaging	Het
Epha7	T	A	4: 28,951,279 (GRCm39)	V800E	probably damaging	Het
Evi5l	A	G	8: 4,255,906 (GRCm39)	Q633R	possibly damaging	Het
Fam170a	T	C	18: 50,414,728 (GRCm39)	Y125H	probably damaging	Het
Fbxo15	T	C	18: 84,980,747 (GRCm39)	Y241H	probably damaging	Het
Gbe1	T	C	16: 70,233,828 (GRCm39)	I235T	possibly damaging	Het
Gfra3	C	T	18: 34,844,234 (GRCm39)	R102Q	probably damaging	Het
Gjd4	C	T	18: 9,280,380 (GRCm39)	G233S	probably damaging	Het
Gm29106	C	T	1: 118,127,291 (GRCm39)	P328S	probably damaging	Het
Hgfac	G	T	5: 35,204,258 (GRCm39)	R507L	probably damaging	Het
Jakmip3	A	G	7: 138,609,355 (GRCm39)	K153R	probably benign	Het
Kcnc1	T	A	7: 46,077,383 (GRCm39)	V395E	probably damaging	Het
Krt6b	T	C	15: 101,586,577 (GRCm39)	D304G	probably damaging	Het
Ldha	T	C	7: 46,500,323 (GRCm39)	Y174H	probably benign	Het
Lgi4	G	A	7: 30,766,776 (GRCm39)	V268M	possibly damaging	Het
Lpar3	T	G	3: 145,947,061 (GRCm39)		probably null	Het
Lrp3	T	C	7: 34,905,477 (GRCm39)	D103G	probably damaging	Het
Marchf5	G	A	19: 37,194,713 (GRCm39)		probably null	Het
Muc5b	A	T	7: 141,419,866 (GRCm39)	H4115L	possibly damaging	Het
Myh13	G	A	11: 67,239,672 (GRCm39)	D741N	probably damaging	Het
Naglu	A	T	11: 100,967,252 (GRCm39)	I401F	probably damaging	Het
Ncam2	T	A	16: 81,309,759 (GRCm39)	N416K	probably damaging	Het
Ncan	A	G	8: 70,564,738 (GRCm39)	L292S	probably damaging	Het
Nkiras1	T	C	14: 18,276,732 (GRCm38)	V7A	probably damaging	Het
Nlrp4c	T	A	7: 6,068,708 (GRCm39)	L203*	probably null	Het
Nscme3l	A	T	19: 5,553,659 (GRCm39)	S41T	possibly damaging	Het
Onecut2	T	A	18: 64,474,633 (GRCm39)	W395R	probably damaging	Het
Or10a2	T	A	7: 106,673,062 (GRCm39)	I9K	probably benign	Het
Pak6	T	A	2: 118,524,003 (GRCm39)	V386E	probably damaging	Het
Pias2	A	G	18: 77,220,931 (GRCm39)	S396G	probably benign	Het
Plxna2	T	A	1: 194,394,568 (GRCm39)	L483H	probably damaging	Het
Prss36	G	T	7: 127,534,763 (GRCm39)	R484S	probably benign	Het
Ptpn21	A	T	12: 98,654,996 (GRCm39)	V657E	probably benign	Het
Rassf2	T	C	2: 131,838,332 (GRCm39)	E318G	probably damaging	Het
Rp1	A	C	1: 4,298,824 (GRCm39)	S623A	unknown	Het
Runx2	G	A	17: 45,125,079 (GRCm39)	P80L	probably damaging	Het
Scn11a	T	A	9: 119,588,982 (GRCm39)	E1308V	probably damaging	Het
Serpina3c	A	T	12: 104,115,771 (GRCm39)	S258T	possibly damaging	Het
Slit3	A	G	11: 35,501,516 (GRCm39)	T417A	possibly damaging	Het
Sostdc1	C	A	12: 36,367,310 (GRCm39)	A162E	possibly damaging	Het
Sox13	A	T	1: 133,312,129 (GRCm39)		probably null	Het
Sox8	G	T	17: 25,786,514 (GRCm39)	S396R	probably benign	Het
Sult2a3	A	T	7: 13,816,685 (GRCm39)	F164L	possibly damaging	Het
Susd2	T	C	10: 75,475,685 (GRCm39)	Y438C	probably damaging	Het
Tas2r106	T	G	6: 131,655,810 (GRCm39)	T14P	probably damaging	Het
Tcf25	T	A	8: 124,127,800 (GRCm39)		probably null	Het
Tenm3	G	A	8: 48,688,970 (GRCm39)	R2206W	probably damaging	Het
Tep1	A	G	14: 51,081,789 (GRCm39)	L471P	unknown	Het
Ticrr	A	T	7: 79,343,490 (GRCm39)	K1118N	probably damaging	Het
Tlr5	G	A	1: 182,801,064 (GRCm39)	E123K	probably benign	Het
Ttn	ATATCTCTCCAGAGCCTCCCCTGGAGGAGTGGAGTATCTCTCCAGAGCCTCCCCTGGAGGAGTGGAGTATCTCTCCAGAGCCTCCCCTG	ATATCTCTCCAGAGCCTCCCCTGGAGGAGTGGAGTATCTCTCCAGAGCCTCCCCTG	2: 76,746,150 (GRCm39)		probably benign	Het
U2surp	A	G	9: 95,375,770 (GRCm39)	V141A	probably benign	Het
Unc79	T	A	12: 103,100,734 (GRCm39)	S2050T	possibly damaging	Het
Usp13	A	G	3: 32,920,020 (GRCm39)	D235G	probably benign	Het
Vcam1	T	C	3: 115,919,628 (GRCm39)	T213A	possibly damaging	Het
Vmn2r60	T	A	7: 41,786,166 (GRCm39)	I323N	possibly damaging	Het
Vps13b	A	G	15: 35,877,703 (GRCm39)	I2892M	probably damaging	Het
Wnt5a	T	A	14: 28,240,329 (GRCm39)	S160T	probably benign	Het
Zar1	G	A	5: 72,738,294 (GRCm39)	P36L	possibly damaging	Het
Zfp773	A	T	7: 7,135,984 (GRCm39)	M204K	probably benign	Het
Zhx1	T	C	15: 57,916,465 (GRCm39)	T594A	probably benign	Het

Other mutations in Duoxa1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02021:Duoxa1	APN	2	122,135,127 (GRCm39)	missense	probably benign	0.35
Minima	UTSW	2	122,134,318 (GRCm39)	missense	probably damaging	1.00
nadir	UTSW	2	122,136,861 (GRCm39)	splice site	probably benign
perigee	UTSW	2	122,135,672 (GRCm39)	nonsense	probably null
R0675:Duoxa1	UTSW	2	122,136,861 (GRCm39)	splice site	probably benign
R0755:Duoxa1	UTSW	2	122,135,161 (GRCm39)	missense	probably benign	0.03
R1387:Duoxa1	UTSW	2	122,134,468 (GRCm39)	missense	possibly damaging	0.82
R2906:Duoxa1	UTSW	2	122,135,155 (GRCm39)	missense	probably benign	0.15
R5327:Duoxa1	UTSW	2	122,134,361 (GRCm39)	missense	probably damaging	0.98
R5886:Duoxa1	UTSW	2	122,134,291 (GRCm39)	missense	possibly damaging	0.82
R6514:Duoxa1	UTSW	2	122,135,194 (GRCm39)	missense	probably benign	0.02
R6841:Duoxa1	UTSW	2	122,134,462 (GRCm39)	missense	probably damaging	1.00
R6845:Duoxa1	UTSW	2	122,135,672 (GRCm39)	nonsense	probably null
R6959:Duoxa1	UTSW	2	122,134,318 (GRCm39)	missense	probably damaging	1.00
R9473:Duoxa1	UTSW	2	122,134,326 (GRCm39)	missense	probably benign
R9717:Duoxa1	UTSW	2	122,135,622 (GRCm39)	missense	probably damaging	1.00
X0017:Duoxa1	UTSW	2	122,135,200 (GRCm39)	missense	probably benign	0.18

Predicted Primers

PCR Primer
(F):5'- ATGGCAGAGGCATAGTGTCC -3'
(R):5'- ACTACAGTTTGCCCAGCAC -3'

Sequencing Primer
(F):5'- AGAGGCATAGTGTCCTGCCAG -3'
(R):5'- AGCACTGGAGCTGGGAG -3'

Posted On

2019-06-26