Mutagenetix > Incidental Mutation

Incidental Mutation 'R6959:Duoxa1'

541634

Institutional Source

Beutler Lab

Gene Symbol

Duoxa1

Ensembl Gene

ENSMUSG00000027224

Gene Name

dual oxidase maturation factor 1

Synonyms

Nip1

MMRRC Submission

045069-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6959 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

122134012-122144255 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 122134318 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Serine to Glycine at position 267 (S267G)

Ref Sequence

ENSEMBL: ENSMUSP00000106167 (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: S312G

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000028653
Gene: ENSMUSG00000027224
AA Change: S312G

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: S312G

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000106166
Gene: ENSMUSG00000027224
AA Change: S312G

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

Predicted Effect

probably damaging
Transcript: ENSMUST00000110538
AA Change: S267G

PolyPhen 2 Score 0.995 (Sensitivity: 0.68; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000106167
Gene: ENSMUSG00000027224
AA Change: S267G

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 benign
Transcript: ENSMUST00000147788

SMART Domains

Protein: ENSMUSP00000116280
Gene: ENSMUSG00000027224

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

Predicted Effect

probably benign
Transcript: ENSMUST00000148417

SMART Domains

Protein: ENSMUSP00000116963
Gene: ENSMUSG00000027224

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

Meta Mutation Damage Score

0.1165

Coding Region Coverage

1x: 100.0%
3x: 99.8%
10x: 99.0%
20x: 96.5%

Validation Efficiency

94% (61/65)

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: 64 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930544D05Rik	G	A	11: 70,507,485 (GRCm39)	G177R	probably damaging	Het
Arhgef12	T	C	9: 42,927,249 (GRCm39)	T292A	probably benign	Het
Atp11a	T	A	8: 12,870,467 (GRCm39)	D173E	probably damaging	Het
Bltp1	T	G	3: 37,021,338 (GRCm39)	V2154G	probably damaging	Het
Btnl2	G	A	17: 34,582,333 (GRCm39)	V300M	possibly damaging	Het
Calcrl	A	T	2: 84,200,428 (GRCm39)	N117K	possibly damaging	Het
Castor2	T	C	5: 134,164,052 (GRCm39)	S83P	probably damaging	Het
Ccdc196	A	G	12: 78,249,070 (GRCm39)	K139E	probably damaging	Het
Ccl22	A	T	8: 95,473,528 (GRCm39)		probably null	Het
Cd200r1	T	A	16: 44,610,539 (GRCm39)	S216T	probably damaging	Het
Cdk5rap2	G	A	4: 70,278,906 (GRCm39)		probably null	Het
Cfap157	A	G	2: 32,674,260 (GRCm39)	I47T	probably damaging	Het
Chodl	G	A	16: 78,743,572 (GRCm39)	V220I	probably damaging	Het
Cntnap5b	A	G	1: 100,202,197 (GRCm39)	E348G	probably benign	Het
Cstf3	A	G	2: 104,479,807 (GRCm39)	T225A	probably benign	Het
Epb41l1	G	A	2: 156,341,507 (GRCm39)	S164N	probably benign	Het
Fat3	T	C	9: 15,908,181 (GRCm39)	D2607G	possibly damaging	Het
Galnt5	A	G	2: 57,889,231 (GRCm39)	D277G	probably benign	Het
Galnt6	A	G	15: 100,612,006 (GRCm39)	I212T	probably damaging	Het
Gm45861	T	C	8: 28,038,213 (GRCm39)		probably null	Het
Gm5478	T	C	15: 101,553,883 (GRCm39)	D243G	probably damaging	Het
Gse1	A	G	8: 121,297,710 (GRCm39)		probably benign	Het
Hspg2	A	T	4: 137,246,600 (GRCm39)	Q1096L	probably benign	Het
Hycc1	T	C	5: 24,196,754 (GRCm39)	I45V	possibly damaging	Het
Idh3b	A	G	2: 130,123,447 (GRCm39)	V181A	probably damaging	Het
Igf2bp3	T	C	6: 49,094,082 (GRCm39)		probably null	Het
Ikzf2	A	G	1: 69,577,929 (GRCm39)	*382Q	probably null	Het
Impg2	A	C	16: 56,088,693 (GRCm39)	H1073P	probably benign	Het
Incenp	T	C	19: 9,854,134 (GRCm39)	E639G	unknown	Het
Kcne4	A	G	1: 78,795,603 (GRCm39)	M84V	probably benign	Het
Ktn1	T	A	14: 47,957,713 (GRCm39)	F1004I	probably damaging	Het
Lrit1	G	C	14: 36,782,052 (GRCm39)	V242L	probably damaging	Het
Malrd1	A	G	2: 16,222,820 (GRCm39)	I2040V	probably damaging	Het
Mau2	T	C	8: 70,485,878 (GRCm39)	D110G	probably damaging	Het
Mei1	T	C	15: 82,009,076 (GRCm39)	V1237A	probably benign	Het
Mfsd11	T	G	11: 116,752,495 (GRCm39)		probably null	Het
Ncapd2	A	G	6: 125,145,883 (GRCm39)	F1293L	probably benign	Het
Nf1	A	G	11: 79,440,294 (GRCm39)	T280A	probably damaging	Het
Obscn	G	T	11: 58,928,411 (GRCm39)	A6085E	probably damaging	Het
Or51b6b	T	A	7: 103,310,050 (GRCm39)	I136F	probably damaging	Het
Pdzd2	C	T	15: 12,375,993 (GRCm39)	A1381T	probably benign	Het
Pramel41	T	A	5: 94,594,891 (GRCm39)	N250K	possibly damaging	Het
Ralgapa2	A	G	2: 146,184,621 (GRCm39)	V1462A	probably damaging	Het
Rbx1	T	A	15: 81,355,163 (GRCm39)	C56*	probably null	Het
Reln	A	G	5: 22,181,562 (GRCm39)	S1774P	probably damaging	Het
Ros1	T	A	10: 52,040,090 (GRCm39)	E300D	probably damaging	Het
Sarnp	T	C	10: 128,684,137 (GRCm39)	V111A	possibly damaging	Het
Scube1	G	T	15: 83,513,636 (GRCm39)	Q345K	probably benign	Het
Slc18b1	A	G	10: 23,701,942 (GRCm39)		probably null	Het
Slc37a2	T	A	9: 37,152,630 (GRCm39)	T64S	probably benign	Het
Slit2	A	G	5: 48,395,727 (GRCm39)	D710G	possibly damaging	Het
Srp72	T	A	5: 77,142,070 (GRCm39)	Y375N	possibly damaging	Het
Tmco4	T	A	4: 138,737,810 (GRCm39)	V135D	probably damaging	Het
Trim62	A	G	4: 128,802,955 (GRCm39)	D335G	probably damaging	Het
Tsfm	T	C	10: 126,858,778 (GRCm39)	M196V	probably benign	Het
Tspan10	T	A	11: 120,335,522 (GRCm39)	C211S	probably damaging	Het
Ttc21b	A	T	2: 66,061,656 (GRCm39)	M498K	probably benign	Het
Ttc6	A	T	12: 57,704,928 (GRCm39)		probably null	Het
Ttll1	G	T	15: 83,386,397 (GRCm39)	Y69*	probably null	Het
Usp28	T	A	9: 48,912,842 (GRCm39)	L31H	probably damaging	Het
Vmn2r86	A	G	10: 130,282,400 (GRCm39)	S739P	probably damaging	Het
Wdr64	T	A	1: 175,533,555 (GRCm39)	F64I	probably damaging	Het
Ywhaq	A	G	12: 21,446,281 (GRCm39)		probably null	Het
Zfr	T	C	15: 12,150,409 (GRCm39)	S459P	probably damaging	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
R7232:Duoxa1	UTSW	2	122,135,728 (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'- CCACTTCCTGGACAGTTCTG -3'
(R):5'- CTGCTCTTAGAAGATCTTGGGAGG -3'

Sequencing Primer
(F):5'- GCTGGTTTTGTGGGGCTCC -3'
(R):5'- CTTAGAAGATCTTGGGAGGACTTAC -3'

Posted On

2018-11-28