Mutagenetix > Incidental Mutation

Incidental Mutation 'R4702:Aff1'

356116

Institutional Source

Beutler Lab

Gene Symbol

Aff1

Ensembl Gene

ENSMUSG00000029313

Gene Name

AF4/FMR2 family, member 1

Synonyms

9630032B01Rik, Af4, Rob, Mllt2h

MMRRC Submission

041950-MU

Accession Numbers

Essential gene?

Possibly non essential (E-score: 0.381) question?

Stock #

R4702 (G1)

Quality Score

225

Status

Not validated

Chromosome

Chromosomal Location

103692374-103855322 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

T to C at 103811069 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Tyrosine to Histidine at position 343 (Y343H)

Ref Sequence

ENSEMBL: ENSMUSP00000119631 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000031256] [ENSMUST00000054979] [ENSMUST00000153165]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000031256
AA Change: Y343H

PolyPhen 2 Score 0.139 (Sensitivity: 0.92; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000031256
Gene: ENSMUSG00000029313
AA Change: Y343H

Domain	Start	End	E-Value	Type
Pfam:AF-4	16	1223	N/A	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000054979
AA Change: Y335H

PolyPhen 2 Score 0.165 (Sensitivity: 0.92; Specificity: 0.87)

SMART Domains

Protein: ENSMUSP00000059744
Gene: ENSMUSG00000029313
AA Change: Y335H

Domain	Start	End	E-Value	Type
Pfam:AF-4	8	1216	N/A	PFAM

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000126335

Predicted Effect

noncoding transcript
Transcript: ENSMUST00000152145

Predicted Effect

probably damaging
Transcript: ENSMUST00000153165
AA Change: Y343H

PolyPhen 2 Score 0.997 (Sensitivity: 0.41; Specificity: 0.98)

SMART Domains

Protein: ENSMUSP00000119631
Gene: ENSMUSG00000029313
AA Change: Y343H

Domain	Start	End	E-Value	Type
Pfam:AF-4	16	871	N/A	PFAM

Coding Region Coverage

1x: 99.2%
3x: 98.6%
10x: 97.1%
20x: 95.1%

Validation Efficiency

MGI Phenotype

FUNCTION: This gene encodes a member of the AF4/ lymphoid nuclear protein related to AF4/Fragile X E mental retardation syndrome family of proteins, which have been implicated in human childhood lymphoblastic leukemia, Fragile X E site mental retardation, and ataxia. It is the prevalent mixed-lineage leukemia fusion gene associated with spontaneous acute lymphoblastic leukemia. Members of this family have three conserved domains: an N-terminal homology domain, an AF4/ lymphoid nuclear protein related to AF4/Fragile X E mental retardation syndrome domain, and a C-terminal homology domain. Knockout of the mouse gene by homologous recombination severely affects early events in lymphopoiesis, including precursor proliferation or recruitment, but is dispensable for terminal differentiation. In addition, an autosomal dominant missense mutation results in several phenotypes including ataxia and adult-onset Purkinje cell loss in the cerebellum, indicating a role in Purkinje cell maintenance and function. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]
PHENOTYPE: Homozygotes for a targeted null mutation exhibit impaired B and T cell development. Heterozygotes for an ENU-induced mutation exhibit small size, ataxia, adult-onset Purkinje cell loss, cataracts, reduced survival, and low fertility. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 75 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
2810474O19Rik	A	G	6: 149,329,403	T1316A	probably benign	Het
4921509C19Rik	T	C	2: 151,472,589	T390A	probably benign	Het
Adam25	G	T	8: 40,754,126	C143F	probably damaging	Het
Adra1a	T	C	14: 66,637,559		probably benign	Het
Antxr2	C	T	5: 97,949,169		probably null	Het
Ap1m2	A	G	9: 21,298,295	F362L	probably benign	Het
Apobec4	A	G	1: 152,756,250	T10A	probably benign	Het
Armc3	A	G	2: 19,309,981	N822S	probably damaging	Het
Atr	A	C	9: 95,920,355	T1767P	possibly damaging	Het
B4galnt1	G	T	10: 127,167,525	V172F	possibly damaging	Het
Bloc1s1	T	A	10: 128,923,398	Q13L	probably damaging	Het
Blvra	A	C	2: 127,092,062	I125L	probably benign	Het
Caps2	T	C	10: 112,208,347	F484L	probably damaging	Het
Cep76	A	T	18: 67,634,898	I188K	possibly damaging	Het
Cidea	T	A	18: 67,367,428	F187I	probably benign	Het
Cntn3	T	A	6: 102,165,331	N1025I	probably benign	Het
Cntnap3	A	T	13: 64,778,862	C565S	probably benign	Het
Cyp2d22	A	C	15: 82,375,917	L22R	probably damaging	Het
Cyp2d26	C	T	15: 82,792,447		probably benign	Het
Cyp2j12	A	T	4: 96,132,993		probably null	Het
Dnajb13	T	C	7: 100,504,541	N229S	probably benign	Het
Dpys	A	G	15: 39,793,402	V423A	possibly damaging	Het
Eif4e1b	A	T	13: 54,787,325	I222F	probably damaging	Het
Eif5b	A	T	1: 38,018,877	N87Y	unknown	Het
Enam	T	A	5: 88,503,791	L1053*	probably null	Het
Epha7	T	A	4: 28,961,425	L890Q	probably damaging	Het
Fancm	T	A	12: 65,122,052	S1730T	possibly damaging	Het
Flrt3	A	G	2: 140,661,655	F18L	probably benign	Het
Git2	A	G	5: 114,745,482	S396P	probably damaging	Het
H2-M10.4	A	G	17: 36,461,982	I36T	probably benign	Het
Igfn1	G	A	1: 135,967,209	S1873L	possibly damaging	Het
Ints12	A	T	3: 133,096,785	D10V	probably damaging	Het
Kbtbd2	A	G	6: 56,779,303	S483P	probably benign	Het
Kcnv2	G	C	19: 27,323,567	A273P	probably damaging	Het
Klc3	T	G	7: 19,395,831	D371A	probably damaging	Het
Lama3	T	A	18: 12,578,029	L1567*	probably null	Het
Ldhal6b	G	T	17: 5,418,307	H117Q	probably damaging	Het
Lrriq1	G	T	10: 103,215,749	Q381K	possibly damaging	Het
Mrps31	T	A	8: 22,419,738	L140Q	probably damaging	Het
Myo15b	A	G	11: 115,884,008	T2119A	probably benign	Het
Nkx6-2	T	C	7: 139,581,540	D243G	probably damaging	Het
Olfr374	T	A	8: 72,110,200	F211L	probably damaging	Het
Olfr918	A	T	9: 38,673,480	M1K	probably null	Het
Papln	C	T	12: 83,781,983	T821I	probably benign	Het
Pitpnb	T	G	5: 111,371,352	V166G	probably benign	Het
Pla2g15	T	A	8: 106,163,059	M321K	probably benign	Het
Plcxd3	C	A	15: 4,375,787	S25R	probably benign	Het
Ppargc1a	T	C	5: 51,495,696	I175V	possibly damaging	Het
Ppp1r13b	T	A	12: 111,833,281	Q687H	probably benign	Het
Prpf3	A	G	3: 95,834,092	V584A	probably damaging	Het
Psen2	A	G	1: 180,227,724	L399S	probably damaging	Het
Ptchd3	G	A	11: 121,836,409	V370I	probably damaging	Het
Rasa3	G	T	8: 13,570,394	D758E	probably benign	Het
Reck	T	C	4: 43,898,060	C113R	probably damaging	Het
Ric1	T	A	19: 29,598,017	F1009I	possibly damaging	Het
Rrp12	T	C	19: 41,871,536	N1035S	probably damaging	Het
Rtel1	T	A	2: 181,352,169	S849T	probably benign	Het
Scn10a	A	T	9: 119,633,791	Y1060N	possibly damaging	Het
Selenov	A	G	7: 28,288,011	L314P	probably damaging	Het
Selplg	T	C	5: 113,819,033	D404G	probably benign	Het
Slc7a14	T	A	3: 31,230,398	Y263F	probably damaging	Het
Slco3a1	A	G	7: 74,320,567	S431P	probably damaging	Het
Speer3	C	G	5: 13,796,380	A238G	possibly damaging	Het
Spopl	A	T	2: 23,515,297		probably null	Het
Stk10	A	T	11: 32,555,172	T69S	probably benign	Het
Tbxas1	T	C	6: 39,083,857		probably null	Het
Tec	G	A	5: 72,783,731	P161L	possibly damaging	Het
Tnip1	A	G	11: 54,924,402	S339P	probably benign	Het
Tsen34	T	A	7: 3,700,633	V290D	probably damaging	Het
Tuba1a	T	A	15: 98,951,682	I5F	possibly damaging	Het
Vmn1r31	C	A	6: 58,471,968	*304L	probably null	Het
Vmn1r63	T	C	7: 5,803,517	R39G	possibly damaging	Het
Xylt2	A	G	11: 94,669,529	Y307H	possibly damaging	Het
Zfp65	A	G	13: 67,724,222	M1T	probably null	Het
Zmym4	T	C	4: 126,923,165	I247V	probably benign	Het

Other mutations in Aff1

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00773:Aff1	APN	5	103784077	missense	probably damaging	1.00
IGL02060:Aff1	APN	5	103783849	missense	possibly damaging	0.51
IGL02081:Aff1	APN	5	103834305	missense	probably damaging	1.00
IGL02108:Aff1	APN	5	103811109	critical splice donor site	probably null
IGL03056:Aff1	APN	5	103811081	missense	probably damaging	0.99
IGL03332:Aff1	APN	5	103841105	nonsense	probably null
IGL03340:Aff1	APN	5	103783804	missense	possibly damaging	0.76
IGL03382:Aff1	APN	5	103841060	missense	possibly damaging	0.86
PIT4495001:Aff1	UTSW	5	103849525	missense	probably benign	0.16
R0013:Aff1	UTSW	5	103828484	nonsense	probably null
R0219:Aff1	UTSW	5	103811040	splice site	probably benign
R0520:Aff1	UTSW	5	103847751	nonsense	probably null
R0607:Aff1	UTSW	5	103828454	missense	probably damaging	1.00
R0883:Aff1	UTSW	5	103826138	splice site	probably benign
R1662:Aff1	UTSW	5	103841057	missense	probably damaging	0.99
R1730:Aff1	UTSW	5	103833512	missense	probably damaging	1.00
R1850:Aff1	UTSW	5	103833907	missense	probably damaging	1.00
R3411:Aff1	UTSW	5	103754706	start codon destroyed	probably null	0.53
R4007:Aff1	UTSW	5	103784222	missense	probably benign	0.15
R4207:Aff1	UTSW	5	103818988	critical splice donor site	probably null
R4730:Aff1	UTSW	5	103843073	missense	possibly damaging	0.95
R4784:Aff1	UTSW	5	103847039	nonsense	probably null
R5166:Aff1	UTSW	5	103754657	start gained	probably benign
R5294:Aff1	UTSW	5	103811157	intron	probably benign
R5435:Aff1	UTSW	5	103754332	unclassified	probably benign
R5436:Aff1	UTSW	5	103783870	missense	probably damaging	1.00
R6065:Aff1	UTSW	5	103842252	missense	probably damaging	1.00
R6114:Aff1	UTSW	5	103842297	missense	probably damaging	0.97
R6298:Aff1	UTSW	5	103754720	missense	possibly damaging	0.68
R7095:Aff1	UTSW	5	103843085	missense	probably damaging	0.97
R7261:Aff1	UTSW	5	103828379	missense	probably damaging	0.97
R7350:Aff1	UTSW	5	103847092	missense	probably benign	0.28
R7423:Aff1	UTSW	5	103847101	missense	probably damaging	1.00
R7469:Aff1	UTSW	5	103833547	missense	probably benign	0.00
R7604:Aff1	UTSW	5	103847809	missense	probably benign	0.09
R7607:Aff1	UTSW	5	103849459	missense	possibly damaging	0.72
R8014:Aff1	UTSW	5	103833869	missense	possibly damaging	0.82
R8219:Aff1	UTSW	5	103846333	missense	probably damaging	1.00
R8315:Aff1	UTSW	5	103811090	missense	probably damaging	0.99
R8837:Aff1	UTSW	5	103834212	missense	possibly damaging	0.77
R8957:Aff1	UTSW	5	103833768	missense	possibly damaging	0.82
R9159:Aff1	UTSW	5	103842265	missense	possibly damaging	0.89
R9377:Aff1	UTSW	5	103833819	missense	probably damaging	0.96
R9381:Aff1	UTSW	5	103833867	missense	possibly damaging	0.85
R9705:Aff1	UTSW	5	103784410	missense	possibly damaging	0.88
R9725:Aff1	UTSW	5	103847065	missense	probably damaging	0.99
R9764:Aff1	UTSW	5	103849499	missense	probably damaging	1.00
Z1177:Aff1	UTSW	5	103783753	missense	possibly damaging	0.71

Predicted Primers

PCR Primer
(F):5'- TGGTCACATTCAGATGGGTGC -3'
(R):5'- TCTCTGGGAAATGAGCACACTC -3'

Sequencing Primer
(F):5'- TCTTCCCCAAGATGAAGTCGGTG -3'
(R):5'- TCCCCAGTCTTTATGGAAAAGCAG -3'

Posted On

2015-10-21