Mutagenetix > Incidental Mutation

Incidental Mutation 'D4043:Duox1'

264

Institutional Source

Beutler Lab

Gene Symbol

Duox1

Ensembl Gene

ENSMUSG00000033268

Gene Name

dual oxidase 1

Synonyms

NOXEF1, LNOX1, 9930101G15Rik, THOX1

Accession Numbers

Essential gene?

Non essential (E-score: 0.000) question?

Stock #

D4043 (G3) of strain 483

Quality Score

Status

Validated

Chromosome

Chromosomal Location

122146153-122178453 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

G to A at 122175276 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Cysteine to Tyrosine at position 1358 (C1358Y)

Ref Sequence

ENSEMBL: ENSMUSP00000097060 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000048635] [ENSMUST00000099461] [ENSMUST00000110530] [ENSMUST00000110531] [ENSMUST00000110532] [ENSMUST00000121237] [ENSMUST00000125826] [ENSMUST00000139819]

AlphaFold

A2AQ92

Predicted Effect

probably benign
Transcript: ENSMUST00000048635

SMART Domains

Protein: ENSMUSP00000045135
Gene: ENSMUSG00000033256

Domain	Start	End	E-Value	Type
low complexity region	48	67	N/A	INTRINSIC
SH2	136	220	9.16e-27	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000099461
AA Change: C1358Y

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)

SMART Domains

Protein: ENSMUSP00000097060
Gene: ENSMUSG00000033268
AA Change: C1358Y

Domain	Start	End	E-Value	Type
signal peptide	1	21	N/A	INTRINSIC
Pfam:An_peroxidase	29	557	2.1e-134	PFAM
transmembrane domain	594	616	N/A	INTRINSIC
EFh	819	847	1.82e-4	SMART
EFh	855	883	3.45e-5	SMART
transmembrane domain	1044	1066	N/A	INTRINSIC
Pfam:Ferric_reduct	1087	1236	5.3e-21	PFAM
Pfam:FAD_binding_8	1272	1374	8.5e-21	PFAM
Pfam:NAD_binding_6	1380	1534	3.5e-33	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000110530

SMART Domains

Protein: ENSMUSP00000106159
Gene: ENSMUSG00000033256

Domain	Start	End	E-Value	Type
low complexity region	42	61	N/A	INTRINSIC
SH2	130	214	9.16e-27	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000110531

SMART Domains

Protein: ENSMUSP00000106160
Gene: ENSMUSG00000033256

Domain	Start	End	E-Value	Type
low complexity region	48	67	N/A	INTRINSIC
SH2	136	220	9.16e-27	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000110532

SMART Domains

Protein: ENSMUSP00000106161
Gene: ENSMUSG00000033256

Domain	Start	End	E-Value	Type
low complexity region	19	38	N/A	INTRINSIC
low complexity region	45	61	N/A	INTRINSIC
low complexity region	77	87	N/A	INTRINSIC
low complexity region	146	165	N/A	INTRINSIC
Blast:SH2	225	278	2e-22	BLAST
SCOP:d1ayaa_	237	291	1e-6	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000121237

SMART Domains

Protein: ENSMUSP00000113923
Gene: ENSMUSG00000033256

Domain	Start	End	E-Value	Type
low complexity region	42	61	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000125826

SMART Domains

Protein: ENSMUSP00000117099
Gene: ENSMUSG00000033256

Domain	Start	End	E-Value	Type
low complexity region	14	56	N/A	INTRINSIC
low complexity region	76	105	N/A	INTRINSIC
low complexity region	129	148	N/A	INTRINSIC
low complexity region	155	171	N/A	INTRINSIC
low complexity region	187	197	N/A	INTRINSIC
low complexity region	256	275	N/A	INTRINSIC
SH2	344	428	9.16e-27	SMART

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000135848

Predicted Effect

probably benign
Transcript: ENSMUST00000151130

SMART Domains

Protein: ENSMUSP00000114524
Gene: ENSMUSG00000033256

Domain	Start	End	E-Value	Type
low complexity region	6	48	N/A	INTRINSIC
low complexity region	68	97	N/A	INTRINSIC
low complexity region	121	140	N/A	INTRINSIC
low complexity region	147	163	N/A	INTRINSIC
low complexity region	179	189	N/A	INTRINSIC
low complexity region	248	267	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000139819

SMART Domains

Protein: ENSMUSP00000119980
Gene: ENSMUSG00000033256

Domain	Start	End	E-Value	Type
low complexity region	14	24	N/A	INTRINSIC
low complexity region	83	102	N/A	INTRINSIC
low complexity region	149	163	N/A	INTRINSIC
SH2	218	302	9.16e-27	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000143484

SMART Domains

Protein: ENSMUSP00000120732
Gene: ENSMUSG00000033256

Domain	Start	End	E-Value	Type
low complexity region	14	33	N/A	INTRINSIC
SH2	71	155	3.19e-26	SMART

Meta Mutation Damage Score

0.0835

Coding Region Coverage

1x: 88.8%
3x: 72.5%

Validation Efficiency

88% (220/249)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a glycoprotein and a member of the NADPH oxidase family. The synthesis of thyroid hormone is catalyzed by a protein complex located at the apical membrane of thyroid follicular cells. This complex contains an iodide transporter, thyroperoxidase, and a peroxide generating system that includes proteins encoded by this gene and the similar DUOX2 gene. This protein is known as dual oxidase because it has both a peroxidase homology domain and a gp91phox domain. This protein generates hydrogen peroxide and thereby plays a role in the activity of thyroid peroxidase, lactoperoxidase, and in lactoperoxidase-mediated antimicrobial defense at mucosal surfaces. Two alternatively spliced transcript variants encoding the same protein have been described for this gene. [provided by RefSeq, Jul 2012]

Allele List at MGI

All alleles(6) : Targeted, other(3) Gene trapped(3)

Other mutations in this stock

Total: 25 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adam29	A	T	8: 56,325,496 (GRCm39)	C319*	probably null	Het
Adgrg1	T	C	8: 95,731,857 (GRCm39)		probably null	Homo
Ago3	A	T	4: 126,244,796 (GRCm39)	V630E	probably damaging	Het
Armc8	G	T	9: 99,366,029 (GRCm39)	N628K	probably benign	Het
Cfap96	A	G	8: 46,409,440 (GRCm39)	V293A	probably damaging	Het
Chd7	A	G	4: 8,862,650 (GRCm39)	D2579G	probably damaging	Het
Ftsj3	C	A	11: 106,145,634 (GRCm39)	M66I	possibly damaging	Homo
Iqub	C	T	6: 24,505,750 (GRCm39)	E53K	possibly damaging	Het
Kirrel1	T	A	3: 86,990,510 (GRCm39)	T771S	probably benign	Het
Lrrc66	A	T	5: 73,764,869 (GRCm39)	S725T	probably benign	Het
Mael	T	C	1: 166,064,455 (GRCm39)	I104M	probably benign	Homo
Mkks	C	T	2: 136,716,530 (GRCm39)	V457I	probably benign	Het
Nadk2	T	A	15: 9,103,473 (GRCm39)		probably benign	Homo
Npas1	T	C	7: 16,197,169 (GRCm39)		probably null	Het
Ocrl	T	C	X: 47,025,200 (GRCm39)	V359A	probably benign	Homo
Or8k27	G	A	2: 86,275,564 (GRCm39)	T254M	probably damaging	Het
Pde6b	C	T	5: 108,573,222 (GRCm39)	R531*	probably null	Het
Polr1a	G	A	6: 71,918,401 (GRCm39)	C653Y	possibly damaging	Het
Rbm26	A	G	14: 105,389,976 (GRCm39)	V216A	possibly damaging	Het
Rin2	C	A	2: 145,664,283 (GRCm39)	H52Q	possibly damaging	Het
Ssc5d	C	T	7: 4,946,982 (GRCm39)	T1112I	possibly damaging	Het
Sv2c	C	T	13: 96,224,989 (GRCm39)	V107M	probably benign	Het
Tasor	A	G	14: 27,193,949 (GRCm39)	I1050V	probably benign	Het
Tulp3	G	A	6: 128,301,113 (GRCm39)	S366L	probably benign	Het
Zfp831	T	A	2: 174,487,059 (GRCm39)	V578E	probably benign	Homo

Other mutations in Duox1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00650:Duox1	APN	2	122,163,622 (GRCm39)	missense	possibly damaging	0.55
IGL00956:Duox1	APN	2	122,153,787 (GRCm39)	missense	probably benign	0.42
IGL01413:Duox1	APN	2	122,151,191 (GRCm39)	missense	probably benign	0.03
IGL01444:Duox1	APN	2	122,170,571 (GRCm39)	missense	probably damaging	0.98
IGL01633:Duox1	APN	2	122,164,279 (GRCm39)	missense	probably benign	0.00
IGL01814:Duox1	APN	2	122,176,753 (GRCm39)	missense	probably damaging	0.99
IGL01868:Duox1	APN	2	122,168,888 (GRCm39)	missense	probably benign
IGL02096:Duox1	APN	2	122,174,655 (GRCm39)	missense	probably damaging	0.99
IGL02126:Duox1	APN	2	122,176,817 (GRCm39)	missense	probably benign	0.21
IGL02342:Duox1	APN	2	122,177,793 (GRCm39)	missense	probably damaging	1.00
IGL02687:Duox1	APN	2	122,166,896 (GRCm39)	missense	probably damaging	1.00
IGL02708:Duox1	APN	2	122,156,498 (GRCm39)	missense	possibly damaging	0.81
IGL02935:Duox1	APN	2	122,155,000 (GRCm39)	missense	possibly damaging	0.56
antiquity	UTSW	2	122,170,682 (GRCm39)	missense	probably damaging	1.00
Dejavous	UTSW	2	122,151,345 (GRCm39)	missense	probably damaging	1.00
R1706_Duox1_051	UTSW	2	122,149,953 (GRCm39)	missense	probably benign	0.01
R5032_duox1_732	UTSW	2	122,167,798 (GRCm39)	missense	probably benign
Vaguely	UTSW	2	122,156,616 (GRCm39)	nonsense	probably null
R0047:Duox1	UTSW	2	122,177,122 (GRCm39)	unclassified	probably benign
R0047:Duox1	UTSW	2	122,177,122 (GRCm39)	unclassified	probably benign
R0241:Duox1	UTSW	2	122,163,878 (GRCm39)	splice site	probably benign
R0479:Duox1	UTSW	2	122,176,861 (GRCm39)	missense	probably damaging	1.00
R0834:Duox1	UTSW	2	122,176,982 (GRCm39)	missense	probably damaging	1.00
R1105:Duox1	UTSW	2	122,168,183 (GRCm39)	missense	probably damaging	0.97
R1205:Duox1	UTSW	2	122,158,406 (GRCm39)	nonsense	probably null
R1281:Duox1	UTSW	2	122,157,569 (GRCm39)	missense	probably damaging	1.00
R1302:Duox1	UTSW	2	122,177,760 (GRCm39)	missense	probably benign	0.24
R1532:Duox1	UTSW	2	122,175,204 (GRCm39)	missense	probably damaging	1.00
R1706:Duox1	UTSW	2	122,149,953 (GRCm39)	missense	probably benign	0.01
R1719:Duox1	UTSW	2	122,169,125 (GRCm39)	missense	possibly damaging	0.93
R1753:Duox1	UTSW	2	122,163,910 (GRCm39)	missense	probably damaging	1.00
R1827:Duox1	UTSW	2	122,177,861 (GRCm39)	nonsense	probably null
R1828:Duox1	UTSW	2	122,177,861 (GRCm39)	nonsense	probably null
R1940:Duox1	UTSW	2	122,156,465 (GRCm39)	missense	probably benign	0.06
R1944:Duox1	UTSW	2	122,177,001 (GRCm39)	missense	probably damaging	0.99
R2069:Duox1	UTSW	2	122,163,543 (GRCm39)	missense	probably benign
R2113:Duox1	UTSW	2	122,167,735 (GRCm39)	missense	probably benign
R2202:Duox1	UTSW	2	122,175,194 (GRCm39)	missense	probably benign	0.19
R2314:Duox1	UTSW	2	122,164,211 (GRCm39)	nonsense	probably null
R2507:Duox1	UTSW	2	122,163,619 (GRCm39)	missense	probably benign	0.34
R2508:Duox1	UTSW	2	122,163,619 (GRCm39)	missense	probably benign	0.34
R3177:Duox1	UTSW	2	122,170,597 (GRCm39)	missense	probably damaging	1.00
R3277:Duox1	UTSW	2	122,170,597 (GRCm39)	missense	probably damaging	1.00
R4124:Duox1	UTSW	2	122,167,902 (GRCm39)	missense	probably damaging	1.00
R4271:Duox1	UTSW	2	122,154,856 (GRCm39)	missense	probably damaging	0.96
R4411:Duox1	UTSW	2	122,168,115 (GRCm39)	missense	probably benign	0.30
R4419:Duox1	UTSW	2	122,157,607 (GRCm39)	missense	probably benign
R4420:Duox1	UTSW	2	122,157,607 (GRCm39)	missense	probably benign
R4578:Duox1	UTSW	2	122,164,258 (GRCm39)	missense	probably benign	0.15
R4628:Duox1	UTSW	2	122,176,733 (GRCm39)	missense	probably damaging	1.00
R4665:Duox1	UTSW	2	122,149,956 (GRCm39)	missense	probably benign	0.00
R4666:Duox1	UTSW	2	122,149,956 (GRCm39)	missense	probably benign	0.00
R4730:Duox1	UTSW	2	122,164,312 (GRCm39)	missense	probably damaging	1.00
R4767:Duox1	UTSW	2	122,163,922 (GRCm39)	missense	possibly damaging	0.79
R4857:Duox1	UTSW	2	122,146,212 (GRCm39)	missense	probably benign	0.05
R4904:Duox1	UTSW	2	122,151,345 (GRCm39)	missense	probably damaging	1.00
R5032:Duox1	UTSW	2	122,167,798 (GRCm39)	missense	probably benign
R5201:Duox1	UTSW	2	122,158,403 (GRCm39)	missense	probably benign
R5474:Duox1	UTSW	2	122,177,106 (GRCm39)	missense	probably benign	0.02
R5835:Duox1	UTSW	2	122,158,341 (GRCm39)	missense	probably benign	0.00
R5939:Duox1	UTSW	2	122,176,832 (GRCm39)	missense	probably damaging	1.00
R5941:Duox1	UTSW	2	122,174,637 (GRCm39)	missense	probably damaging	0.97
R5943:Duox1	UTSW	2	122,163,916 (GRCm39)	missense	probably benign	0.00
R5970:Duox1	UTSW	2	122,170,682 (GRCm39)	missense	probably damaging	1.00
R6023:Duox1	UTSW	2	122,168,165 (GRCm39)	missense	probably benign	0.19
R6050:Duox1	UTSW	2	122,149,956 (GRCm39)	missense	probably benign	0.00
R6064:Duox1	UTSW	2	122,151,243 (GRCm39)	missense	probably benign	0.00
R6093:Duox1	UTSW	2	122,177,755 (GRCm39)	missense	probably benign	0.01
R6188:Duox1	UTSW	2	122,150,275 (GRCm39)	missense	probably benign	0.00
R6246:Duox1	UTSW	2	122,157,655 (GRCm39)	missense	probably damaging	1.00
R6259:Duox1	UTSW	2	122,175,264 (GRCm39)	missense	probably benign	0.00
R6290:Duox1	UTSW	2	122,164,288 (GRCm39)	missense	possibly damaging	0.92
R6300:Duox1	UTSW	2	122,168,181 (GRCm39)	missense	probably damaging	0.99
R6341:Duox1	UTSW	2	122,168,202 (GRCm39)	missense	probably damaging	0.98
R6498:Duox1	UTSW	2	122,150,088 (GRCm39)	missense	probably damaging	1.00
R6883:Duox1	UTSW	2	122,155,065 (GRCm39)	splice site	probably null
R7002:Duox1	UTSW	2	122,150,358 (GRCm39)	nonsense	probably null
R7410:Duox1	UTSW	2	122,176,874 (GRCm39)	missense	probably damaging	1.00
R7421:Duox1	UTSW	2	122,153,711 (GRCm39)	missense	probably damaging	1.00
R7608:Duox1	UTSW	2	122,156,616 (GRCm39)	nonsense	probably null
R7702:Duox1	UTSW	2	122,160,120 (GRCm39)	missense	possibly damaging	0.86
R7766:Duox1	UTSW	2	122,167,782 (GRCm39)	missense	probably benign
R7833:Duox1	UTSW	2	122,154,869 (GRCm39)	missense	probably damaging	1.00
R7980:Duox1	UTSW	2	122,177,801 (GRCm39)	missense	possibly damaging	0.71
R8275:Duox1	UTSW	2	122,175,249 (GRCm39)	missense	probably benign	0.02
R8717:Duox1	UTSW	2	122,168,152 (GRCm39)	missense	possibly damaging	0.88
R8992:Duox1	UTSW	2	122,175,186 (GRCm39)	missense	probably damaging	1.00
R9196:Duox1	UTSW	2	122,150,689 (GRCm39)	missense	probably benign	0.08
R9344:Duox1	UTSW	2	122,168,163 (GRCm39)	missense	probably benign	0.14
R9397:Duox1	UTSW	2	122,150,783 (GRCm39)	missense	possibly damaging	0.48
R9491:Duox1	UTSW	2	122,156,907 (GRCm39)	missense	probably benign	0.01
R9510:Duox1	UTSW	2	122,160,023 (GRCm39)	missense	possibly damaging	0.92
R9521:Duox1	UTSW	2	122,159,216 (GRCm39)	missense	possibly damaging	0.81
R9562:Duox1	UTSW	2	122,151,203 (GRCm39)	missense	probably damaging	1.00
R9565:Duox1	UTSW	2	122,151,203 (GRCm39)	missense	probably damaging	1.00
R9569:Duox1	UTSW	2	122,148,971 (GRCm39)	missense	probably benign
Z1176:Duox1	UTSW	2	122,163,519 (GRCm39)	missense	probably damaging	0.99

Nature of Mutation

DNA sequencing using the SOLiD technique identified a G to A transition at position 4104 of the Duox1 transcript in exon 29 of 33 total exons. The mutated nucleotide causes a cysteine to tyrosine substitution at amino acid 1358 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Duox1 gene encodes a 1551 amino acid oxidoreductase that is involved in the synthesis of thyroid hormone (Uniprot A2AQ92). As predicted by SMART, the protein contains several domains including an N-terminal ferric oxidoreductase domain, followed by a transmembrane domain, two calcium-binding EF hands, and C-terminal FAD (flavin adenine dinucleotide)- and NAD (nicotinamide adenine dinucleotide)-binding domains.

The C1358Y change is located in the FAD-binding domain, and is predicted to be benign by the PolyPhen program.

Posted On

2010-08-09