Mutagenetix > Incidental Mutation

Incidental Mutation 'R8941:Dio1'

680974

Institutional Source

Beutler Lab

Gene Symbol

Dio1

Ensembl Gene

ENSMUSG00000034785

Gene Name

deiodinase, iodothyronine, type I

Synonyms

MMRRC Submission

068781-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.366) question?

Stock #

R8941 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

107148662-107164365 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

C to A at 107164147 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Alanine to Serine at position 57 (A57S)

Ref Sequence

ENSEMBL: ENSMUSP00000121450 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000082426] [ENSMUST00000106748] [ENSMUST00000126291] [ENSMUST00000129138] [ENSMUST00000134366] [ENSMUST00000147709] [ENSMUST00000150974]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000082426
AA Change: A57S

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

SMART Domains

Protein: ENSMUSP00000081007
Gene: ENSMUSG00000034785
AA Change: A57S

Domain	Start	End	E-Value	Type
Pfam:T4_deiodinase	8	248	8.8e-106	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000106748
AA Change: A57S

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

SMART Domains

Protein: ENSMUSP00000102359
Gene: ENSMUSG00000034785
AA Change: A57S

Domain	Start	End	E-Value	Type
Pfam:T4_deiodinase	8	113	1.1e-24	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000126291

SMART Domains

Protein: ENSMUSP00000114807
Gene: ENSMUSG00000034785

Domain	Start	End	E-Value	Type
Pfam:T4_deiodinase	1	62	8.3e-31	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000129138
AA Change: A57S

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

SMART Domains

Protein: ENSMUSP00000118335
Gene: ENSMUSG00000034785
AA Change: A57S

Domain	Start	End	E-Value	Type
Pfam:T4_deiodinase	8	113	7e-24	PFAM
Pfam:T4_deiodinase	111	200	5.3e-42	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000134366
AA Change: A57S

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000119199
Gene: ENSMUSG00000034785
AA Change: A57S

Domain	Start	End	E-Value	Type
Pfam:T4_deiodinase	8	79	9.2e-10	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000147709
AA Change: A57S

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)

SMART Domains

Protein: ENSMUSP00000121450
Gene: ENSMUSG00000034785
AA Change: A57S

Domain	Start	End	E-Value	Type
Pfam:T4_deiodinase	8	79	9.2e-10	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000150974
AA Change: A57S

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

SMART Domains

Protein: ENSMUSP00000117751
Gene: ENSMUSG00000034785
AA Change: A57S

Domain	Start	End	E-Value	Type
Pfam:T4_deiodinase	8	125	2.5e-34	PFAM

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.7%
20x: 99.1%

Validation Efficiency

100% (59/59)

MGI Phenotype

FUNCTION: The protein encoded by this gene belongs to the iodothyronine deiodinase family. It catalyzes the activation, as well as the inactivation of thyroid hormone by outer and inner ring deiodination, respectively. The activation reaction involves the conversion of the prohormone thyroxine (3,5,3',5'-tetraiodothyronine, T4), secreted by the thyroid gland, to the bioactive thyroid hormone (3,5,3'-triiodothyronine, T3) by 5'-deiodination. This protein is expressed predominantly in the liver and kidney and provides most of the circulating T3, which is essential for growth, differentiation and basal metabolism in vertebrates. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec) at its active site. Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. [provided by RefSeq, Apr 2016]
PHENOTYPE: Mice homozygous for a disruption in this gene display elevated thyroxine (T4) and reverse triiodothyronine (rT3) levels and changes in the metabolism and excretion of iodothyronines. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 59 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2010315B03Rik	T	A	9: 124,056,679 (GRCm39)	T103S	probably benign	Het
Aadacl2fm3	A	G	3: 59,784,400 (GRCm39)	Y291C	probably damaging	Het
Aass	A	T	6: 23,075,261 (GRCm39)		probably benign	Het
Adgrb3	A	T	1: 25,133,235 (GRCm39)	C1284S	probably damaging	Het
Adora2a	G	A	10: 75,169,559 (GRCm39)	W341*	probably null	Het
Afg2a	T	A	3: 37,486,142 (GRCm39)	L288H	probably damaging	Het
Arap1	G	A	7: 101,057,324 (GRCm39)	R1355Q	possibly damaging	Het
Asic5	A	T	3: 81,913,915 (GRCm39)		probably benign	Het
Canx	T	C	11: 50,195,270 (GRCm39)	D266G	possibly damaging	Het
Cfap57	A	T	4: 118,426,799 (GRCm39)	Y1080N	probably damaging	Het
Chat	C	T	14: 32,130,963 (GRCm39)	M559I	probably benign	Het
Chd5	G	A	4: 152,463,305 (GRCm39)	S1425N	possibly damaging	Het
Cog8	T	C	8: 107,783,202 (GRCm39)	D29G	probably damaging	Het
Cox15	A	G	19: 43,732,172 (GRCm39)	S215P	probably benign	Het
Cramp1	C	T	17: 25,202,114 (GRCm39)	G456D	probably damaging	Het
Dbt	T	C	3: 116,339,698 (GRCm39)	V362A	probably damaging	Het
F5	C	A	1: 164,026,440 (GRCm39)	H1671N	probably benign	Het
Gm6309	A	G	5: 146,107,155 (GRCm39)	Y64H	probably damaging	Het
Hipk1	A	G	3: 103,660,743 (GRCm39)	C731R	probably damaging	Het
Hmgcl	G	A	4: 135,683,015 (GRCm39)	A156T	probably damaging	Het
Il15ra	A	T	2: 11,737,995 (GRCm39)	T210S	possibly damaging	Het
Kat8	T	C	7: 127,524,400 (GRCm39)	L426P	probably damaging	Het
Lrrc39	G	T	3: 116,359,496 (GRCm39)	V14L	probably damaging	Het
Lrrc7	T	C	3: 157,869,593 (GRCm39)	M709V	probably benign	Het
Mdm4	T	C	1: 132,919,671 (GRCm39)	H398R	probably benign	Het
Mroh2b	A	T	15: 4,991,606 (GRCm39)	Q1568L	possibly damaging	Het
Myo18b	G	A	5: 113,022,795 (GRCm39)		probably benign	Het
Nr4a3	C	A	4: 48,051,756 (GRCm39)	P170Q	possibly damaging	Het
Ntrk2	A	G	13: 59,208,109 (GRCm39)	M652V	probably damaging	Het
Or10n7-ps1	A	T	9: 39,597,812 (GRCm39)	*143K	probably null	Het
Or5b95	G	A	19: 12,657,471 (GRCm39)		probably benign	Het
Paxbp1	T	C	16: 90,832,815 (GRCm39)	I325V	possibly damaging	Het
Pcare	T	C	17: 72,059,137 (GRCm39)	H180R	probably benign	Het
Pi4ka	G	T	16: 17,114,807 (GRCm39)		probably benign	Het
Pira13	A	G	7: 3,825,380 (GRCm39)	S421P	probably damaging	Het
Pou6f1	T	A	15: 100,489,742 (GRCm39)	D74V	probably damaging	Het
Prpsap2	C	A	11: 61,627,870 (GRCm39)	R202L	probably damaging	Het
Ptprn	A	T	1: 75,228,407 (GRCm39)	L890Q	probably damaging	Het
Ramp1	C	G	1: 91,134,137 (GRCm39)	P97A	probably benign	Het
Rapgefl1	A	G	11: 98,731,101 (GRCm39)	D179G	probably damaging	Het
Rbp3	T	A	14: 33,678,486 (GRCm39)	F811L	possibly damaging	Het
Rnf213	C	A	11: 119,305,250 (GRCm39)	L494M	probably damaging	Het
Rpl4	A	G	9: 64,082,245 (GRCm39)	N48S	probably benign	Het
Rsbn1l	A	G	5: 21,110,841 (GRCm39)	V499A	probably damaging	Het
Sacs	A	G	14: 61,430,022 (GRCm39)	T691A	probably benign	Het
Sass6	T	C	3: 116,407,709 (GRCm39)	V275A	probably benign	Het
Sdcbp	T	C	4: 6,393,661 (GRCm39)	S259P	probably benign	Het
Sephs2	A	G	7: 126,872,206 (GRCm39)	F296L	probably benign	Het
Slc12a4	C	T	8: 106,673,322 (GRCm39)		probably null	Het
Snrk	G	A	9: 121,989,597 (GRCm39)	V314I	probably benign	Het
Tas1r3	C	T	4: 155,947,600 (GRCm39)		probably null	Het
Tle3	T	A	9: 61,320,195 (GRCm39)	V560E	probably damaging	Het
Trdmt1	A	G	2: 13,526,918 (GRCm39)	Y144H	probably benign	Het
Trim42	T	C	9: 97,245,100 (GRCm39)	T567A	probably benign	Het
Tsbp1	A	C	17: 34,678,973 (GRCm39)	R228S	possibly damaging	Het
Tuba4a	T	C	1: 75,193,945 (GRCm39)	D74G	probably benign	Het
Ube3c	G	A	5: 29,842,769 (GRCm39)		probably null	Het
Vwa3a	A	G	7: 120,375,311 (GRCm39)	D375G	probably benign	Het
Zfp729b	A	G	13: 67,741,218 (GRCm39)	M349T	possibly damaging	Het

Other mutations in Dio1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL02332:Dio1	APN	4	107,150,978 (GRCm39)	missense	probably damaging	1.00
IGL02476:Dio1	APN	4	107,149,574 (GRCm39)	missense	probably damaging	1.00
R1944:Dio1	UTSW	4	107,163,977 (GRCm39)	critical splice donor site	probably null
R5400:Dio1	UTSW	4	107,164,185 (GRCm39)	missense	probably damaging	0.97
R5433:Dio1	UTSW	4	107,163,977 (GRCm39)	critical splice donor site	probably benign
R6810:Dio1	UTSW	4	107,154,922 (GRCm39)	missense	probably damaging	1.00
R6978:Dio1	UTSW	4	107,164,030 (GRCm39)	missense	probably benign	0.20
R7485:Dio1	UTSW	4	107,154,874 (GRCm39)	missense	probably benign	0.04
R7579:Dio1	UTSW	4	107,149,583 (GRCm39)	missense	possibly damaging	0.91
R9255:Dio1	UTSW	4	107,164,102 (GRCm39)	missense	probably damaging	0.97
R9621:Dio1	UTSW	4	107,149,558 (GRCm39)	missense	probably benign	0.00

Predicted Primers

PCR Primer
(F):5'- CTGACCTTGAATGAAATCCCAGATG -3'
(R):5'- TAGCCTGCACCTTTGTCCAG -3'

Sequencing Primer
(F):5'- GAAATCCCAGATGTTGCACTTCTG -3'
(R):5'- TTCAGTCTGCAGGCTCAGAG -3'

Posted On

2021-08-31