Mutagenetix > Incidental Mutation

Incidental Mutation 'A4554:Dido1'

110

Institutional Source

Beutler Lab

Gene Symbol

Dido1

Ensembl Gene

ENSMUSG00000038914

Gene Name

death inducer-obliterator 1

Synonyms

D130048F08Rik, Datf1, 6720461J16Rik, dido, DIO-1, C130092D22Rik

Accession Numbers

Essential gene?

Probably essential (E-score: 0.960) question?

Stock #

A4554 of strain gemini

Quality Score

Status

Validated

Chromosome

Chromosomal Location

180299757-180351792 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 180317164 bp (GRCm39)

Zygosity

Homozygous

Amino Acid Change

Lysine to Glutamic Acid at position 8 (K8E)

Ref Sequence

ENSEMBL: ENSMUSP00000048315 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000037764] [ENSMUST00000087517] [ENSMUST00000103056] [ENSMUST00000103057]

AlphaFold

Q8C9B9

Predicted Effect

probably damaging
Transcript: ENSMUST00000037764
AA Change: K8E

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000048315
Gene: ENSMUSG00000038914
AA Change: K8E

Domain	Start	End	E-Value	Type
TFS2M	129	230	1.16e-45	SMART
low complexity region	397	422	N/A	INTRINSIC
low complexity region	483	497	N/A	INTRINSIC
Pfam:SPOC	512	618	4.9e-23	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000087517
AA Change: K548E

PolyPhen 2 Score 0.259 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000084794
Gene: ENSMUSG00000038914
AA Change: K548E

Domain	Start	End	E-Value	Type
low complexity region	134	155	N/A	INTRINSIC
PHD	267	317	1.19e-11	SMART
low complexity region	430	446	N/A	INTRINSIC
TFS2M	669	770	1.16e-45	SMART
low complexity region	937	962	N/A	INTRINSIC
low complexity region	1023	1037	N/A	INTRINSIC
Pfam:SPOC	1052	1158	1e-22	PFAM
low complexity region	1253	1267	N/A	INTRINSIC
low complexity region	1279	1308	N/A	INTRINSIC
low complexity region	1372	1391	N/A	INTRINSIC
coiled coil region	1458	1502	N/A	INTRINSIC
low complexity region	1649	1680	N/A	INTRINSIC
low complexity region	1748	1766	N/A	INTRINSIC
low complexity region	1780	1792	N/A	INTRINSIC
low complexity region	1804	1815	N/A	INTRINSIC
internal_repeat_2	1816	1852	3.9e-5	PROSPERO
internal_repeat_1	1819	1859	6.92e-7	PROSPERO
internal_repeat_2	1926	1964	3.9e-5	PROSPERO
internal_repeat_1	1940	1982	6.92e-7	PROSPERO
low complexity region	2025	2045	N/A	INTRINSIC
low complexity region	2123	2160	N/A	INTRINSIC
low complexity region	2163	2177	N/A	INTRINSIC
low complexity region	2182	2239	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000103056
AA Change: K548E

PolyPhen 2 Score 0.259 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000099345
Gene: ENSMUSG00000038914
AA Change: K548E

Domain	Start	End	E-Value	Type
low complexity region	134	155	N/A	INTRINSIC
PHD	267	317	1.19e-11	SMART
low complexity region	430	446	N/A	INTRINSIC
TFS2M	669	770	1.16e-45	SMART
low complexity region	937	962	N/A	INTRINSIC
low complexity region	1023	1037	N/A	INTRINSIC
Pfam:SPOC	1052	1158	4.7e-23	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000103057
AA Change: K548E

PolyPhen 2 Score 0.259 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000099346
Gene: ENSMUSG00000038914
AA Change: K548E

Domain	Start	End	E-Value	Type
low complexity region	134	155	N/A	INTRINSIC
PHD	267	317	1.19e-11	SMART
low complexity region	430	446	N/A	INTRINSIC
TFS2M	669	770	1.16e-45	SMART
low complexity region	937	962	N/A	INTRINSIC
low complexity region	1023	1037	N/A	INTRINSIC
Pfam:SPOC	1052	1158	4.7e-23	PFAM

Meta Mutation Damage Score

0.0670

Coding Region Coverage

1x: 85.5%
3x: 63.0%

Validation Efficiency

84% (92/109)

MGI Phenotype

FUNCTION: This gene encodes a transcription factor involved in apoptosis. The encoded protein functions in cell cycle progression and plays a role in chromosomal stability. This protein regulates the self-renewal of embryonic stem cells. Disruption of this gene in mice causes symptoms similar to myelodysplastic/myeloproliferative diseases in humans. Mice lacking this gene show severely reduced fertility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit severely reduced fertility; about one-half develop a transplantable disease characterized by anomalies in spleen, bone marrow, and peripheral blood and including anemia and various symptoms typical of myeloid dysplasia or myeloid proliferation. [provided by MGI curators]

Allele List at MGI

All alleles(245) : Targeted, knock-out(1) Gene trapped(244)

Other mutations in this stock

Total: 18 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Asap1	T	C	15: 63,996,560 (GRCm39)		probably benign	Het
Bpifb5	A	T	2: 154,069,100 (GRCm39)	Y139F	possibly damaging	Homo
Chd2	A	C	7: 73,130,716 (GRCm39)	V782G	probably benign	Homo
Chst4	G	T	8: 110,756,520 (GRCm39)	Q448K	probably benign	Homo
Evpl	A	G	11: 116,111,660 (GRCm39)	L2010P	probably damaging	Homo
Fgl2	A	G	5: 21,577,776 (GRCm39)	E21G	probably benign	Homo
Greb1l	A	T	18: 10,532,862 (GRCm39)	M919L	possibly damaging	Homo
Kel	T	A	6: 41,674,353 (GRCm39)	D359V	possibly damaging	Homo
Lmtk2	A	G	5: 144,103,135 (GRCm39)	D298G	possibly damaging	Homo
Masp1	A	T	16: 23,273,690 (GRCm39)		probably null	Homo
Mrgprb8	A	T	7: 48,039,156 (GRCm39)	I276F	probably damaging	Homo
Nde1	T	C	16: 14,006,274 (GRCm39)		probably benign	Homo
Rbck1	G	T	2: 152,161,092 (GRCm39)	N385K	probably damaging	Homo
Senp6	G	T	9: 80,055,740 (GRCm39)		probably benign	Het
Tm4sf4	T	A	3: 57,345,188 (GRCm39)		probably null	Homo
Ubn2	A	T	6: 38,461,045 (GRCm39)	H488L	probably damaging	Homo
Vmn2r120	A	G	17: 57,832,715 (GRCm39)	F155L	probably benign	Homo
Vmn2r65	T	A	7: 84,595,791 (GRCm39)	T298S	probably damaging	Homo

Other mutations in Dido1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00425:Dido1	APN	2	180,325,782 (GRCm39)	missense	probably benign
IGL00834:Dido1	APN	2	180,331,319 (GRCm39)	missense	possibly damaging	0.87
IGL01317:Dido1	APN	2	180,313,550 (GRCm39)	missense	probably benign	0.17
IGL01588:Dido1	APN	2	180,330,668 (GRCm39)	missense	probably benign	0.00
IGL01834:Dido1	APN	2	180,325,824 (GRCm39)	splice site	probably benign
IGL02102:Dido1	APN	2	180,304,040 (GRCm39)	missense	possibly damaging	0.58
IGL02556:Dido1	APN	2	180,331,128 (GRCm39)	missense	possibly damaging	0.69
IGL02756:Dido1	APN	2	180,303,716 (GRCm39)	missense	probably benign	0.00
IGL02826:Dido1	APN	2	180,325,751 (GRCm39)	missense	probably benign
IGL02970:Dido1	APN	2	180,331,208 (GRCm39)	missense	probably damaging	0.99
IGL03110:Dido1	APN	2	180,331,135 (GRCm39)	missense	probably damaging	1.00
IGL03116:Dido1	APN	2	180,312,772 (GRCm39)	missense	probably damaging	1.00
3370:Dido1	UTSW	2	180,313,335 (GRCm39)	missense	probably benign
H8441:Dido1	UTSW	2	180,330,807 (GRCm39)	missense	probably benign	0.12
R0044:Dido1	UTSW	2	180,303,612 (GRCm39)	missense	probably damaging	1.00
R0044:Dido1	UTSW	2	180,303,612 (GRCm39)	missense	probably damaging	1.00
R0054:Dido1	UTSW	2	180,303,267 (GRCm39)	missense	probably benign	0.00
R0054:Dido1	UTSW	2	180,303,267 (GRCm39)	missense	probably benign	0.00
R0127:Dido1	UTSW	2	180,313,617 (GRCm39)	missense	probably benign	0.01
R0620:Dido1	UTSW	2	180,301,644 (GRCm39)	missense	probably benign	0.26
R0734:Dido1	UTSW	2	180,301,835 (GRCm39)	missense	probably benign	0.01
R1390:Dido1	UTSW	2	180,326,917 (GRCm39)	missense	possibly damaging	0.70
R1445:Dido1	UTSW	2	180,313,263 (GRCm39)	missense	possibly damaging	0.62
R1466:Dido1	UTSW	2	180,304,121 (GRCm39)	missense	probably damaging	1.00
R1466:Dido1	UTSW	2	180,304,121 (GRCm39)	missense	probably damaging	1.00
R1472:Dido1	UTSW	2	180,302,513 (GRCm39)	missense	probably benign	0.02
R1538:Dido1	UTSW	2	180,326,763 (GRCm39)	missense	possibly damaging	0.49
R1584:Dido1	UTSW	2	180,304,121 (GRCm39)	missense	probably damaging	1.00
R2020:Dido1	UTSW	2	180,301,378 (GRCm39)	missense	unknown
R2025:Dido1	UTSW	2	180,330,974 (GRCm39)	nonsense	probably null
R2026:Dido1	UTSW	2	180,330,974 (GRCm39)	nonsense	probably null
R2027:Dido1	UTSW	2	180,330,974 (GRCm39)	nonsense	probably null
R2089:Dido1	UTSW	2	180,303,677 (GRCm39)	missense	probably benign	0.29
R2091:Dido1	UTSW	2	180,303,677 (GRCm39)	missense	probably benign	0.29
R2091:Dido1	UTSW	2	180,303,677 (GRCm39)	missense	probably benign	0.29
R2495:Dido1	UTSW	2	180,331,181 (GRCm39)	missense	probably benign	0.00
R2931:Dido1	UTSW	2	180,303,446 (GRCm39)	missense	probably damaging	1.00
R3418:Dido1	UTSW	2	180,302,728 (GRCm39)	missense	possibly damaging	0.84
R3735:Dido1	UTSW	2	180,325,829 (GRCm39)	splice site	probably benign
R4523:Dido1	UTSW	2	180,314,085 (GRCm39)	missense	probably damaging	1.00
R4674:Dido1	UTSW	2	180,329,352 (GRCm39)	missense	probably damaging	0.97
R4729:Dido1	UTSW	2	180,329,443 (GRCm39)	missense	probably benign	0.00
R4762:Dido1	UTSW	2	180,331,368 (GRCm39)	missense	probably damaging	1.00
R4786:Dido1	UTSW	2	180,312,664 (GRCm39)	missense	possibly damaging	0.85
R4817:Dido1	UTSW	2	180,303,209 (GRCm39)	missense	probably benign	0.02
R4892:Dido1	UTSW	2	180,316,822 (GRCm39)	nonsense	probably null
R4979:Dido1	UTSW	2	180,302,606 (GRCm39)	missense	probably damaging	0.98
R5510:Dido1	UTSW	2	180,326,966 (GRCm39)	missense	probably benign	0.00
R5586:Dido1	UTSW	2	180,301,445 (GRCm39)	nonsense	probably null
R5672:Dido1	UTSW	2	180,313,696 (GRCm39)	missense	probably damaging	0.99
R5863:Dido1	UTSW	2	180,303,566 (GRCm39)	missense	probably benign	0.02
R5943:Dido1	UTSW	2	180,303,675 (GRCm39)	missense	probably benign	0.00
R5974:Dido1	UTSW	2	180,313,290 (GRCm39)	missense	probably benign	0.02
R6123:Dido1	UTSW	2	180,325,760 (GRCm39)	missense	probably benign	0.07
R6214:Dido1	UTSW	2	180,303,945 (GRCm39)	missense	probably damaging	1.00
R6215:Dido1	UTSW	2	180,303,945 (GRCm39)	missense	probably damaging	1.00
R6248:Dido1	UTSW	2	180,302,048 (GRCm39)	missense	probably damaging	1.00
R6285:Dido1	UTSW	2	180,302,940 (GRCm39)	missense	probably benign	0.00
R6349:Dido1	UTSW	2	180,302,494 (GRCm39)	missense	probably benign	0.03
R6437:Dido1	UTSW	2	180,316,806 (GRCm39)	missense	probably damaging	1.00
R6477:Dido1	UTSW	2	180,302,274 (GRCm39)	missense	probably benign	0.00
R6836:Dido1	UTSW	2	180,304,100 (GRCm39)	missense	probably benign	0.16
R7055:Dido1	UTSW	2	180,303,002 (GRCm39)	missense	probably benign	0.09
R7289:Dido1	UTSW	2	180,301,424 (GRCm39)	missense	unknown
R7304:Dido1	UTSW	2	180,329,286 (GRCm39)	missense	probably damaging	1.00
R7343:Dido1	UTSW	2	180,316,914 (GRCm39)	missense	possibly damaging	0.49
R7363:Dido1	UTSW	2	180,304,310 (GRCm39)	nonsense	probably null
R7429:Dido1	UTSW	2	180,331,319 (GRCm39)	missense	possibly damaging	0.87
R7594:Dido1	UTSW	2	180,316,905 (GRCm39)	missense	probably benign
R7629:Dido1	UTSW	2	180,303,266 (GRCm39)	missense	probably benign
R7899:Dido1	UTSW	2	180,313,390 (GRCm39)	missense	possibly damaging	0.82
R7946:Dido1	UTSW	2	180,303,501 (GRCm39)	missense	possibly damaging	0.81
R7951:Dido1	UTSW	2	180,312,674 (GRCm39)	missense	probably benign	0.01
R8033:Dido1	UTSW	2	180,316,635 (GRCm39)	missense	probably damaging	1.00
R8069:Dido1	UTSW	2	180,302,705 (GRCm39)	missense	probably benign
R8331:Dido1	UTSW	2	180,302,242 (GRCm39)	missense	probably benign	0.00
R8479:Dido1	UTSW	2	180,315,022 (GRCm39)	critical splice donor site	probably null
R8936:Dido1	UTSW	2	180,303,195 (GRCm39)	missense	probably benign
R9089:Dido1	UTSW	2	180,303,293 (GRCm39)	missense	probably benign	0.00
R9647:Dido1	UTSW	2	180,315,068 (GRCm39)	missense	probably benign	0.00
R9648:Dido1	UTSW	2	180,302,468 (GRCm39)	missense	probably damaging	1.00
R9784:Dido1	UTSW	2	180,325,354 (GRCm39)	missense	probably benign	0.27
V1024:Dido1	UTSW	2	180,330,807 (GRCm39)	missense	probably benign	0.12
X0011:Dido1	UTSW	2	180,302,627 (GRCm39)	missense	probably benign	0.00
X0019:Dido1	UTSW	2	180,313,365 (GRCm39)	missense	possibly damaging	0.62

Nature of Mutation

DNA sequencing using the SOLiD technique identified an A to G transition at position 3263 of the Dido1 transcript in exon 13 of 17 total exons. Multiple transcripts of the Dido1 gene are displayed on Ensembl. The mutated nucleotide causes a lysine to glutamic acid substitution at amino acid 548 of isoform 3 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction

The Dido1 gene encodes at least three protein isoforms, Dido1, Dido2, and Dido3. Dido3 is the largest and most dominantly expressed protein isoform with 2256 amino acids. The Dido proteins contain one PHD-type zinc finger at amino acids 265-319, and a transcription elongation factor S-II (TFIIS) central domain at amino acids 667-787. PHD-type zinc fingers are typically involved in chromatin-mediated transcriptional regulation. Dido1 is a putative transcription factor that is upregulated during apoptosis, and translocates to the nucleus in response to pro-apoptotic stimuli. It is weakly pro-apoptotic when overexpressed (Uniprot Q8C9B9). Mice homozygous for a null allele of Dido1 exhibit myelodysplasia and a myeloproliferative disorder. Humans with similar disorders display abnormalities in Dido expression. Dido3 associates with centrosomes, and a specific disruption in Dido3 leads to supernumerary centrosomes, and a failure to maintain mitotic arrest resulting in enhanced aneuploidy in Dido mutant cells. The amino acid mutated in Gemini mice is present only in the Dido2 and Dido3 isoforms.

The K548E change is predicted to be benign by the PolyPhen program.

Posted On

2010-03-16