Mutagenetix > Incidental Mutation

Incidental Mutation 'R5436:Aff1'

428331

Institutional Source

Beutler Lab

Gene Symbol

Aff1

Ensembl Gene

ENSMUSG00000029313

Gene Name

AF4/FMR2 family, member 1

Synonyms

9630032B01Rik, Af4, Rob, Mllt2h

MMRRC Submission

043001-MU

Accession Numbers

Essential gene?

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

Stock #

R5436 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

103692374-103855322 bp(+) (GRCm38)

Type of Mutation

missense

DNA Base Change (assembly)

C to T at 103783870 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Threonine to Isoleucine at position 126 (T126I)

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 damaging
Transcript: ENSMUST00000031256
AA Change: T126I

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000031256
Gene: ENSMUSG00000029313
AA Change: T126I

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

Predicted Effect

possibly damaging
Transcript: ENSMUST00000054979
AA Change: T118I

PolyPhen 2 Score 0.931 (Sensitivity: 0.81; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000059744
Gene: ENSMUSG00000029313
AA Change: T118I

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: T126I

PolyPhen 2 Score 1.000 (Sensitivity: 0.00; Specificity: 1.00)

SMART Domains

Protein: ENSMUSP00000119631
Gene: ENSMUSG00000029313
AA Change: T126I

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

Meta Mutation Damage Score

0.1550

Coding Region Coverage

1x: 99.3%
3x: 98.6%
10x: 97.3%
20x: 95.4%

Validation Efficiency

99% (106/107)

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: 100 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
4930402H24Rik	C	A	2: 130,764,499	K415N	probably benign	Het
4930449A18Rik	T	C	3: 59,846,693		noncoding transcript	Het
Abca9	G	A	11: 110,134,236	L994F	probably damaging	Het
Abl2	A	T	1: 156,629,880	S239C	probably damaging	Het
Acsl5	T	A	19: 55,279,565		probably null	Het
Amtn	T	C	5: 88,381,626	L107P	probably damaging	Het
Ankrd45	A	G	1: 161,159,112		probably benign	Het
Arl6ip5	G	A	6: 97,210,926	V36I	probably damaging	Het
Ascc3	T	A	10: 50,658,983	D657E	probably damaging	Het
Ascl1	T	A	10: 87,492,946	Q48L	unknown	Het
Asic4	T	A	1: 75,451,319	V163E	probably benign	Het
Atm	A	T	9: 53,459,804	M2245K	probably benign	Het
Barx2	T	G	9: 31,912,989	T35P	probably damaging	Het
BC027072	A	T	17: 71,750,842	S613R	probably damaging	Het
Bdh1	C	T	16: 31,456,657	R235C	probably damaging	Het
C8b	T	A	4: 104,800,349	Y404*	probably null	Het
Car5a	A	G	8: 121,917,242		probably benign	Het
Ccdc13	T	C	9: 121,799,043	I169M	probably benign	Het
Cd163	A	T	6: 124,327,964	D1100V	probably benign	Het
Cntfr	T	C	4: 41,663,322	N162D	probably damaging	Het
Cops3	T	G	11: 59,824,345	D289A	probably damaging	Het
Crbn	A	T	6: 106,795,900	S42R	probably damaging	Het
Cth	T	A	3: 157,894,826	H397L	probably benign	Het
Dact2	A	G	17: 14,195,748	L730P	probably damaging	Het
Dhx37	C	T	5: 125,429,803	G210R	probably benign	Het
Dnah1	T	C	14: 31,316,747	I126V	probably benign	Het
Dnttip2	T	C	3: 122,278,769	I566T	probably damaging	Het
Ehbp1l1	G	T	19: 5,716,248	R412S	possibly damaging	Het
Fam110b	A	C	4: 5,799,104	Q174P	probably benign	Het
Fam149a	A	T	8: 45,348,471	S457T	probably benign	Het
Fat3	A	C	9: 15,960,514	V3527G	probably benign	Het
Fat4	A	G	3: 38,891,346	M1463V	probably benign	Het
Gak	T	A	5: 108,592,352	I566F	possibly damaging	Het
Gdf10	T	A	14: 33,932,256	I240N	probably damaging	Het
Gprc6a	T	A	10: 51,626,702	H355L	probably benign	Het
Gxylt1	T	C	15: 93,247,899	K338R	probably damaging	Het
Hexim2	A	T	11: 103,138,269	E49V	probably null	Het
Hfm1	T	C	5: 106,892,772	D709G	possibly damaging	Het
Ighv1-49	T	C	12: 115,055,461	K19R	probably damaging	Het
Il17a	T	A	1: 20,733,646	Y88*	probably null	Het
Iqsec1	A	T	6: 90,845,361		probably benign	Het
Itih2	T	C	2: 10,105,196	D582G	probably benign	Het
Klc3	T	C	7: 19,397,959		probably null	Het
Larp4	T	A	15: 99,986,114	N78K	probably damaging	Het
Larp4b	A	G	13: 9,168,900	D526G	possibly damaging	Het
Lexm	A	T	4: 106,610,493	H315Q	probably benign	Het
Limch1	T	C	5: 66,974,566	V133A	possibly damaging	Het
Lmbr1l	G	A	15: 98,904,791	R426C	probably damaging	Het
Lox	T	A	18: 52,529,103	D76V	probably benign	Het
Lrrc8d	T	A	5: 105,812,552	I276N	probably damaging	Het
Ltbr	G	A	6: 125,312,794	R146W	probably damaging	Het
March10	A	T	11: 105,402,165	Y139N	possibly damaging	Het
Mrc1	T	G	2: 14,266,515	I410S	probably damaging	Het
Mrto4	A	T	4: 139,347,965	C176S	probably damaging	Het
Mtch1	G	T	17: 29,347,590	D66E	probably benign	Het
Nbas	T	G	12: 13,374,811	L1017R	probably damaging	Het
Nim1k	A	G	13: 119,727,529		probably benign	Het
Nlrp6	T	A	7: 140,922,717	Y245*	probably null	Het
Olfr1264	T	A	2: 90,021,665	M134L	probably benign	Het
Olfr192	C	T	16: 59,098,819	V58I	unknown	Het
Olfr224	T	A	11: 58,566,937	H136L	probably benign	Het
Olfr635	A	T	7: 103,979,266	I25F	probably benign	Het
Olfr740	T	G	14: 50,453,727	V225G	probably damaging	Het
Olfr906	A	C	9: 38,488,539	D170A	probably benign	Het
Pcnx	G	T	12: 81,860,406	G12V	probably damaging	Het
Pdzd3	A	G	9: 44,248,355	V448A	possibly damaging	Het
Pkp1	T	A	1: 135,918,918	K32M	probably damaging	Het
Poc5	T	C	13: 96,396,813	W150R	probably damaging	Het
Ppp1r16b	T	A	2: 158,757,333		probably benign	Het
Prune2	T	A	19: 17,020,643	M248K	probably damaging	Het
Rb1	A	T	14: 73,213,140		probably null	Het
Rhod	A	G	19: 4,426,587	C169R	probably benign	Het
Rif1	T	C	2: 52,120,971		probably benign	Het
Rnpc3	G	A	3: 113,624,999	A100V	probably damaging	Het
Rsf1	GCGGC	GCGGCGGCGTCGGC	7: 97,579,931		probably benign	Het
Scnn1a	A	T	6: 125,343,022	D528V	possibly damaging	Het
Sdhaf3	C	A	6: 7,038,855	T59K	probably benign	Het
Sec31a	C	A	5: 100,363,839	A330S	probably damaging	Het
Sgk3	A	G	1: 9,881,872	D241G	probably damaging	Het
Skint6	T	G	4: 113,096,591	I459L	probably benign	Het
Slco1a5	A	T	6: 142,254,392	V222E	probably damaging	Het
Slit3	T	A	11: 35,707,911	N1447K	probably benign	Het
Sorbs2	A	G	8: 45,796,001	H628R	probably damaging	Het
St6galnac2	A	G	11: 116,684,527		probably benign	Het
Tbc1d31	T	C	15: 57,952,871	V667A	probably benign	Het
Tbx20	A	T	9: 24,769,720	Y159N	probably damaging	Het
Tmprss11b	T	A	5: 86,662,233	Q296L	probably benign	Het
Ttc6	T	A	12: 57,674,594		probably null	Het
Ttn	T	A	2: 76,870,899		probably benign	Het
Tubgcp4	T	A	2: 121,188,136	L340H	probably damaging	Het
Tubgcp4	T	A	2: 121,194,182	F613I	probably benign	Het
Urb1	T	C	16: 90,792,762	Y377C	probably damaging	Het
Utp15	G	A	13: 98,260,846		probably null	Het
Vstm2b	A	G	7: 40,901,283		probably null	Het
Vwde	A	T	6: 13,190,628	V488D	probably damaging	Het
Wee1	TCCCC	TCCC	7: 110,124,569		probably null	Het
Zfp276	A	T	8: 123,265,282		probably benign	Het
Zfp318	T	A	17: 46,413,049	S1993T	possibly damaging	Het
Zfp959	T	C	17: 55,897,626	L218P	probably benign	Het
Zxdc	A	G	6: 90,370,560	D301G	probably damaging	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
R4702:Aff1	UTSW	5	103811069	missense	probably damaging	1.00
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
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'- CATGCTGGGTGACTATGAGG -3'
(R):5'- CTGCAGCCTGGAATGTACAG -3'

Sequencing Primer
(F):5'- CATGCTGGGTGACTATGAGGAGATG -3'
(R):5'- TTCCTCTCGGGAGCAGAGTCTC -3'

Posted On

2016-09-01