Mutagenetix > Incidental Mutation

Incidental Mutation 'R6915:Runx1t1'

539270

Institutional Source

Beutler Lab

Gene Symbol

Runx1t1

Ensembl Gene

ENSMUSG00000006586

Gene Name

RUNX1 translocation partner 1

Synonyms

ETO, Cbfa2t1h, MTG8

MMRRC Submission

045036-MU

Accession Numbers

Essential gene?

Probably essential (E-score: 0.837) question?

Stock #

R6915 (G1)

Quality Score

225.009

Status

Validated

Chromosome

Chromosomal Location

13743436-13893649 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

T to A at 13865257 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Tryptophan to Arginine at position 350 (W350R)

Ref Sequence

ENSEMBL: ENSMUSP00000127109 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000006761] [ENSMUST00000098256] [ENSMUST00000098257] [ENSMUST00000105566]

AlphaFold

Q61909

Predicted Effect

probably damaging
Transcript: ENSMUST00000006761
AA Change: W330R

PolyPhen 2 Score 0.968 (Sensitivity: 0.77; Specificity: 0.95)

SMART Domains

Protein: ENSMUSP00000006761
Gene: ENSMUSG00000006586
AA Change: W330R

Domain	Start	End	E-Value	Type
low complexity region	32	48	N/A	INTRINSIC
low complexity region	68	96	N/A	INTRINSIC
TAFH	102	192	1.12e-53	SMART
low complexity region	266	277	N/A	INTRINSIC
Pfam:NHR2	317	383	6.9e-42	PFAM
SCOP:d1gpua1	384	454	7e-3	SMART
PDB:2KYG\|C	417	447	2e-12	PDB
Pfam:zf-MYND	495	531	4e-10	PFAM
low complexity region	543	558	N/A	INTRINSIC
low complexity region	562	583	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000098256
AA Change: W323R

PolyPhen 2 Score 0.225 (Sensitivity: 0.91; Specificity: 0.88)

SMART Domains

Protein: ENSMUSP00000095856
Gene: ENSMUSG00000006586
AA Change: W323R

Domain	Start	End	E-Value	Type
low complexity region	25	41	N/A	INTRINSIC
low complexity region	61	89	N/A	INTRINSIC
TAFH	95	185	1.12e-53	SMART
low complexity region	259	270	N/A	INTRINSIC
Pfam:NHR2	310	376	7.3e-42	PFAM
SCOP:d1gpua1	377	447	7e-3	SMART
PDB:2KYG\|C	410	440	2e-12	PDB
Pfam:zf-MYND	488	524	2.5e-10	PFAM
low complexity region	536	551	N/A	INTRINSIC
low complexity region	555	576	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000098257
AA Change: W350R

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000095857
Gene: ENSMUSG00000006586
AA Change: W350R

Domain	Start	End	E-Value	Type
low complexity region	52	68	N/A	INTRINSIC
low complexity region	88	116	N/A	INTRINSIC
TAFH	122	212	1.12e-53	SMART
low complexity region	286	297	N/A	INTRINSIC
Pfam:NHR2	337	403	5.2e-43	PFAM
SCOP:d1gpua1	404	474	7e-3	SMART
PDB:2KYG\|C	437	467	2e-12	PDB
Pfam:zf-MYND	515	551	6.7e-10	PFAM
low complexity region	563	578	N/A	INTRINSIC
low complexity region	582	603	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000105566
AA Change: W350R

PolyPhen 2 Score 0.991 (Sensitivity: 0.71; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000127109
Gene: ENSMUSG00000006586
AA Change: W350R

Domain	Start	End	E-Value	Type
low complexity region	52	68	N/A	INTRINSIC
low complexity region	88	116	N/A	INTRINSIC
TAFH	122	212	1.12e-53	SMART
low complexity region	286	297	N/A	INTRINSIC
Pfam:NHR2	337	403	3.6e-42	PFAM
SCOP:d1gpua1	404	474	7e-3	SMART
PDB:2KYG\|C	437	467	2e-12	PDB
Pfam:zf-MYND	515	551	1.4e-10	PFAM
low complexity region	563	578	N/A	INTRINSIC
low complexity region	582	603	N/A	INTRINSIC

Meta Mutation Damage Score

0.3525

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.2%
20x: 97.3%

Validation Efficiency

97% (63/65)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the myeloid translocation gene family which interact with DNA-bound transcription factors and recruit a range of corepressors to facilitate transcriptional repression. The t(8;21)(q22;q22) translocation is one of the most frequent karyotypic abnormalities in acute myeloid leukemia. The translocation produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 gene fused to the 3'-region of this gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]
PHENOTYPE: Homozygous disruption of this gene results in increased perinatal lethality and surviving animals show severe growth retardation. The midgut is absent in 25% of mutant animals which could explain increased perinatal mortality. Surviving animals display thinned intestinal walls and dilated lumens. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 63 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adck1	C	A	12: 88,422,390 (GRCm39)	L334I	probably damaging	Het
Akap9	T	A	5: 4,010,551 (GRCm39)	M436K	probably benign	Het
Ankmy1	A	C	1: 92,816,173 (GRCm39)	F314V	probably null	Het
Arid5b	G	A	10: 68,022,042 (GRCm39)	Q183*	probably null	Het
Atp8b4	A	T	2: 126,200,834 (GRCm39)	L778*	probably null	Het
BC024139	G	T	15: 76,004,221 (GRCm39)	N739K	probably benign	Het
Carns1	T	G	19: 4,219,912 (GRCm39)	H441P	probably benign	Het
Cby2	T	A	14: 75,830,098 (GRCm39)	T32S	probably benign	Het
Ccdc121rt3	A	T	5: 112,502,523 (GRCm39)	W394R	probably damaging	Het
Cfap70	T	A	14: 20,459,153 (GRCm39)	I693F	probably benign	Het
Cldn3	A	G	5: 135,015,426 (GRCm39)	Q43R	probably damaging	Het
Col7a1	C	T	9: 108,796,686 (GRCm39)	P1608L	probably benign	Het
Cr2	T	A	1: 194,853,454 (GRCm39)	Y28F	probably benign	Het
Cyp2c38	T	A	19: 39,424,512 (GRCm39)	I269F	probably damaging	Het
Dapk1	A	T	13: 60,844,256 (GRCm39)	I92F	probably damaging	Het
Dennd4a	T	A	9: 64,759,771 (GRCm39)	L292*	probably null	Het
Dhx38	T	C	8: 110,286,231 (GRCm39)	E353G	probably benign	Het
Dnm3	T	C	1: 162,145,966 (GRCm39)		probably null	Het
Dzip3	T	C	16: 48,762,488 (GRCm39)	I794V	possibly damaging	Het
Eif2b5	T	A	16: 20,321,500 (GRCm39)	V351D	possibly damaging	Het
Epg5	T	A	18: 78,022,380 (GRCm39)	V1041E	probably benign	Het
Exoc4	A	G	6: 33,898,388 (GRCm39)	K869R	possibly damaging	Het
Fat3	C	A	9: 16,289,044 (GRCm39)	V160F	probably benign	Het
Gak	A	T	5: 108,750,816 (GRCm39)	Y365N	probably benign	Het
Ghrhr	T	A	6: 55,360,104 (GRCm39)		probably null	Het
Gm21738	A	G	14: 19,415,933 (GRCm38)	M202T	probably benign	Het
Havcr2	C	T	11: 46,366,738 (GRCm39)	S177L	probably benign	Het
Hkdc1	G	C	10: 62,237,711 (GRCm39)	R353G	possibly damaging	Het
Ifi208	G	A	1: 173,510,444 (GRCm39)	G200S	probably damaging	Het
Klhl20	T	C	1: 160,921,266 (GRCm39)	D63G	possibly damaging	Het
Lair1	A	T	7: 4,058,952 (GRCm39)	V12E	possibly damaging	Het
Lipo3	T	C	19: 33,562,293 (GRCm39)	N26D	probably damaging	Het
Lyst	T	A	13: 13,900,629 (GRCm39)	D3168E	probably benign	Het
Map6	G	A	7: 98,917,454 (GRCm39)	A76T	probably damaging	Het
Mcoln3	A	T	3: 145,843,011 (GRCm39)		probably null	Het
Muc4	T	C	16: 32,587,312 (GRCm39)	F2718L	probably benign	Het
Nek11	C	G	9: 105,270,256 (GRCm39)		probably benign	Het
Or10n7-ps1	T	C	9: 39,597,832 (GRCm39)	E136G	unknown	Het
Or2z8	C	A	8: 72,811,574 (GRCm39)	L17I	probably benign	Het
Or4d6	A	G	19: 12,086,490 (GRCm39)	V140A	probably benign	Het
Pcdh15	A	T	10: 74,479,641 (GRCm39)	E846V	probably benign	Het
Pcdhga8	C	T	18: 37,858,998 (GRCm39)	T18M	probably benign	Het
Per3	T	C	4: 151,128,106 (GRCm39)	M61V	possibly damaging	Het
Pfas	C	T	11: 68,883,007 (GRCm39)	R759Q	probably benign	Het
Pitpnm1	A	G	19: 4,156,947 (GRCm39)	Y490C	possibly damaging	Het
Plcb4	A	T	2: 135,789,035 (GRCm39)	I272F	possibly damaging	Het
Ppp1r3b	A	G	8: 35,851,821 (GRCm39)	Y220C	probably damaging	Het
Prkce	G	C	17: 86,800,835 (GRCm39)	G417A	probably damaging	Het
Ptar1	A	G	19: 23,680,501 (GRCm39)	N106D	probably damaging	Het
Rbm15	C	A	3: 107,239,627 (GRCm39)	R257L	probably benign	Het
Rptor	T	G	11: 119,647,171 (GRCm39)	M254R	probably damaging	Het
Ryr2	T	G	13: 11,760,487 (GRCm39)	Y1532S	probably damaging	Het
Serpina1a	C	A	12: 103,820,110 (GRCm39)	V379L	possibly damaging	Het
Sox8	C	T	17: 25,786,888 (GRCm39)	V272I	probably damaging	Het
Stard9	C	T	2: 120,533,111 (GRCm39)	H3123Y	probably benign	Het
Taar9	C	T	10: 23,984,910 (GRCm39)	E175K	possibly damaging	Het
Tinag	T	A	9: 76,908,897 (GRCm39)	Y348F	probably damaging	Het
Tktl2	T	C	8: 66,965,687 (GRCm39)	I415T	probably damaging	Het
Tm7sf2	G	T	19: 6,118,342 (GRCm39)	R718S	probably damaging	Het
Tmem229a	G	T	6: 24,954,657 (GRCm39)	Q366K	probably benign	Het
Txndc2	T	C	17: 65,945,286 (GRCm39)	D297G	probably benign	Het
Ulk4	A	G	9: 121,087,886 (GRCm39)	F269L	probably benign	Het
Vps39	A	T	2: 120,151,512 (GRCm39)	Y738*	probably null	Het

Other mutations in Runx1t1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00425:Runx1t1	APN	4	13,835,663 (GRCm39)	missense	probably benign	0.07
IGL01600:Runx1t1	APN	4	13,841,871 (GRCm39)	missense	probably damaging	1.00
IGL02120:Runx1t1	APN	4	13,846,884 (GRCm39)	missense	probably benign
IGL02172:Runx1t1	APN	4	13,859,924 (GRCm39)	missense	probably benign	0.00
IGL02429:Runx1t1	APN	4	13,865,294 (GRCm39)	splice site	probably benign
IGL02730:Runx1t1	APN	4	13,860,019 (GRCm39)	missense	probably benign	0.01
IGL02870:Runx1t1	APN	4	13,889,867 (GRCm39)	missense	unknown
IGL02879:Runx1t1	APN	4	13,889,868 (GRCm39)	missense	unknown
IGL03369:Runx1t1	APN	4	13,881,107 (GRCm39)	missense	probably damaging	1.00
IGL03047:Runx1t1	UTSW	4	13,865,882 (GRCm39)	missense	probably damaging	1.00
R1832:Runx1t1	UTSW	4	13,835,628 (GRCm39)	splice site	probably benign
R1884:Runx1t1	UTSW	4	13,835,767 (GRCm39)	missense	probably benign	0.00
R2277:Runx1t1	UTSW	4	13,771,501 (GRCm39)	missense	probably benign	0.00
R4059:Runx1t1	UTSW	4	13,889,769 (GRCm39)	missense	probably benign	0.33
R4505:Runx1t1	UTSW	4	13,889,676 (GRCm39)	missense	probably damaging	1.00
R4585:Runx1t1	UTSW	4	13,889,864 (GRCm39)	missense	unknown
R4586:Runx1t1	UTSW	4	13,889,864 (GRCm39)	missense	unknown
R4758:Runx1t1	UTSW	4	13,865,907 (GRCm39)	missense	probably damaging	1.00
R4795:Runx1t1	UTSW	4	13,837,767 (GRCm39)	missense	probably damaging	0.99
R4796:Runx1t1	UTSW	4	13,837,767 (GRCm39)	missense	probably damaging	0.99
R4897:Runx1t1	UTSW	4	13,771,459 (GRCm39)	start codon destroyed	probably null	0.01
R4971:Runx1t1	UTSW	4	13,837,978 (GRCm39)	missense	probably damaging	1.00
R5009:Runx1t1	UTSW	4	13,865,231 (GRCm39)	missense	possibly damaging	0.80
R5091:Runx1t1	UTSW	4	13,846,830 (GRCm39)	nonsense	probably null
R5844:Runx1t1	UTSW	4	13,881,068 (GRCm39)	missense	probably damaging	1.00
R5968:Runx1t1	UTSW	4	13,841,890 (GRCm39)	splice site	probably null
R5993:Runx1t1	UTSW	4	13,875,490 (GRCm39)	missense	probably benign	0.00
R5993:Runx1t1	UTSW	4	13,841,863 (GRCm39)	missense	probably damaging	0.98
R6329:Runx1t1	UTSW	4	13,785,136 (GRCm39)	start codon destroyed	probably null	0.38
R7283:Runx1t1	UTSW	4	13,846,935 (GRCm39)	missense	probably damaging	1.00
R8251:Runx1t1	UTSW	4	13,846,947 (GRCm39)	missense	possibly damaging	0.46
R9301:Runx1t1	UTSW	4	13,875,477 (GRCm39)	missense	possibly damaging	0.78
R9376:Runx1t1	UTSW	4	13,865,225 (GRCm39)	missense	possibly damaging	0.93
R9390:Runx1t1	UTSW	4	13,865,932 (GRCm39)	missense	probably benign	0.14
Z1088:Runx1t1	UTSW	4	13,865,892 (GRCm39)	missense	possibly damaging	0.52

Predicted Primers

PCR Primer
(F):5'- GAAGGCACCTACCAGAGTCATTATG -3'
(R):5'- AAGACAGTGGCCTGCTGATC -3'

Sequencing Primer
(F):5'- AGAGTCATTATGTGTTCACATCCCG -3'
(R):5'- GCTGATCTGCCTTCTCCCAAG -3'

Posted On

2018-11-06