Mutagenetix > Incidental Mutation

Incidental Mutation 'R4957:Tcf7l2'

381687

Institutional Source

Beutler Lab

Gene Symbol

Tcf7l2

Ensembl Gene

ENSMUSG00000024985

Gene Name

transcription factor 7 like 2, T cell specific, HMG box

Synonyms

TCF4B, mTcf-4B, mTcf-4E, TCF4E, Tcf4, Tcf-4

MMRRC Submission

042554-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R4957 (G1)

Quality Score

225

Status

Validated

Chromosome

Chromosomal Location

55741810-55933654 bp(+) (GRCm38)

Type of Mutation

critical splice acceptor site

DNA Base Change (assembly)

A to G at 55931432 bp (GRCm38)

Zygosity

Heterozygous

Amino Acid Change

Ref Sequence

ENSEMBL: ENSMUSP00000118661 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000041717] [ENSMUST00000061496] [ENSMUST00000111646] [ENSMUST00000111656] [ENSMUST00000111657] [ENSMUST00000111658] [ENSMUST00000111659] [ENSMUST00000111662] [ENSMUST00000153888] [ENSMUST00000153888]

AlphaFold

no structure available at present

Predicted Effect

probably null
Transcript: ENSMUST00000041717

SMART Domains

Protein: ENSMUSP00000042950
Gene: ENSMUSG00000024985

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	236	1.5e-95	PFAM
HMG	326	396	1.16e-22	SMART
low complexity region	402	410	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000061496

SMART Domains

Protein: ENSMUSP00000050081
Gene: ENSMUSG00000024985

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	236	1.7e-95	PFAM
HMG	326	396	1.16e-22	SMART
low complexity region	402	410	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000111646

SMART Domains

Protein: ENSMUSP00000107273
Gene: ENSMUSG00000024985

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	76	2.4e-37	PFAM
HMG	166	236	1.16e-22	SMART
low complexity region	242	250	N/A	INTRINSIC
c-clamp	278	298	2.25e-1	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000111656

SMART Domains

Protein: ENSMUSP00000107283
Gene: ENSMUSG00000024985

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	236	1.5e-95	PFAM
HMG	326	396	1.16e-22	SMART
low complexity region	402	410	N/A	INTRINSIC
c-clamp	438	458	2.25e-1	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000111657

SMART Domains

Protein: ENSMUSP00000107284
Gene: ENSMUSG00000024985

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	236	2.1e-95	PFAM
HMG	326	396	1.16e-22	SMART
low complexity region	402	410	N/A	INTRINSIC
c-clamp	438	468	2.08e-14	SMART
low complexity region	471	498	N/A	INTRINSIC
low complexity region	519	539	N/A	INTRINSIC
low complexity region	564	578	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000111658

SMART Domains

Protein: ENSMUSP00000107286
Gene: ENSMUSG00000024985

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	259	4.5e-93	PFAM
HMG	350	420	1.16e-22	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000111659

SMART Domains

Protein: ENSMUSP00000107287
Gene: ENSMUSG00000024985

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	236	1.7e-96	PFAM
HMG	331	401	1.16e-22	SMART
low complexity region	407	415	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000111662

SMART Domains

Protein: ENSMUSP00000107291
Gene: ENSMUSG00000024985

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	236	1.7e-103	PFAM
HMG	326	396	1.16e-22	SMART
low complexity region	402	410	N/A	INTRINSIC
c-clamp	421	442	1.23e-2	SMART
c-clamp	446	476	1.35e-13	SMART
low complexity region	479	506	N/A	INTRINSIC
low complexity region	527	547	N/A	INTRINSIC
low complexity region	572	586	N/A	INTRINSIC

Predicted Effect

probably null
Transcript: ENSMUST00000127233

SMART Domains

Protein: ENSMUSP00000123428
Gene: ENSMUSG00000024985

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	229	9.3e-98	PFAM
HMG	319	389	1.16e-22	SMART
low complexity region	395	403	N/A	INTRINSIC
c-clamp	414	434	2.25e-1	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000127233

SMART Domains

Protein: ENSMUSP00000123428
Gene: ENSMUSG00000024985

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	229	9.3e-98	PFAM
HMG	319	389	1.16e-22	SMART
low complexity region	395	403	N/A	INTRINSIC
c-clamp	414	434	2.25e-1	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000127233

SMART Domains

Protein: ENSMUSP00000123428
Gene: ENSMUSG00000024985

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	229	9.3e-98	PFAM
HMG	319	389	1.16e-22	SMART
low complexity region	395	403	N/A	INTRINSIC
c-clamp	414	434	2.25e-1	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000127233

SMART Domains

Protein: ENSMUSP00000123428
Gene: ENSMUSG00000024985

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	229	9.3e-98	PFAM
HMG	319	389	1.16e-22	SMART
low complexity region	395	403	N/A	INTRINSIC
c-clamp	414	434	2.25e-1	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000153888

SMART Domains

Protein: ENSMUSP00000118661
Gene: ENSMUSG00000024985

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	217	1.2e-64	PFAM
HMG	307	377	1.16e-22	SMART
low complexity region	383	391	N/A	INTRINSIC
c-clamp	402	432	5.29e-7	SMART

Predicted Effect

probably null
Transcript: ENSMUST00000153888

SMART Domains

Protein: ENSMUSP00000118661
Gene: ENSMUSG00000024985

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	217	1.2e-64	PFAM
HMG	307	377	1.16e-22	SMART
low complexity region	383	391	N/A	INTRINSIC
c-clamp	402	432	5.29e-7	SMART

Meta Mutation Damage Score

0.9490

Coding Region Coverage

1x: 99.1%
3x: 98.3%
10x: 96.3%
20x: 92.5%

Validation Efficiency

99% (80/81)

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a high mobility group (HMG) box-containing transcription factor that plays a key role in the Wnt signaling pathway. The protein has been implicated in blood glucose homeostasis. Genetic variants of this gene are associated with increased risk of type 2 diabetes. Several transcript variants encoding multiple different isoforms have been found for this gene.[provided by RefSeq, Oct 2010]
PHENOTYPE: Animals homozygous for a targeted mutation exhibit intestinal epithelia abnormalities and die shortly after birth. Mice heterozygous for some mutations display abnormalities in glucose homeostasis. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 69 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
3110009E18Rik	G	C	1: 120,169,110		probably benign	Het
3110009E18Rik	G	T	1: 120,169,119		probably benign	Het
3110009E18Rik	C	T	1: 120,169,120		probably benign	Het
6820408C15Rik	T	A	2: 152,444,093	V342D	probably damaging	Het
Arhgap33	C	T	7: 30,532,361	G101R	probably damaging	Het
Atf7ip	C	T	6: 136,606,810	R1280C	probably damaging	Het
Cacnb4	T	C	2: 52,558,291	H8R	probably damaging	Het
Ccdc150	T	A	1: 54,364,868		probably benign	Het
Cd163l1	T	C	7: 140,228,522	V782A	probably damaging	Het
Cd74	A	G	18: 60,809,037	N113D	probably benign	Het
Cdc25b	T	C	2: 131,193,605	V341A	possibly damaging	Het
Clptm1l	T	A	13: 73,611,196	I245N	possibly damaging	Het
Clptm1l	T	C	13: 73,612,428	I310T	probably damaging	Het
Creb5	A	T	6: 53,693,922		probably null	Het
Crebbp	T	C	16: 4,117,367	Q460R	probably benign	Het
Dnah17	A	T	11: 118,074,298	I2306N	probably benign	Het
Dync1h1	C	A	12: 110,658,126	T3700N	probably damaging	Het
Elovl1	A	T	4: 118,431,923	H215L	probably damaging	Het
Enkd1	A	G	8: 105,704,489	I202T	probably benign	Het
Epha7	C	T	4: 28,871,892	A407V	probably damaging	Het
Ercc3	G	T	18: 32,243,117	G130W	probably damaging	Het
Fbxl8	A	G	8: 105,268,195	E113G	probably damaging	Het
Frmpd1	T	G	4: 45,273,099	N339K	probably damaging	Het
Frrs1	G	A	3: 116,885,248	D240N	probably benign	Het
Gemin2	A	G	12: 59,017,168	S105G	probably benign	Het
Glra1	T	A	11: 55,527,398	I257F	probably damaging	Het
Gmcl1	G	A	6: 86,710,521	P354S	probably damaging	Het
Gpr15	G	T	16: 58,718,174	A184E	probably damaging	Het
Grm7	G	A	6: 111,358,863	G745E	probably damaging	Het
H2-T10	T	A	17: 36,117,416		probably benign	Het
Hdac5	C	A	11: 102,205,256		probably benign	Het
Ift22	G	A	5: 136,908,216		probably benign	Het
Ighg3	T	C	12: 113,361,130	E34G	unknown	Het
Itga11	A	T	9: 62,767,648	T821S	probably benign	Het
Lmod2	T	C	6: 24,603,872	V282A	possibly damaging	Het
Maml2	A	G	9: 13,620,276	K262R	probably damaging	Het
Mme	T	A	3: 63,343,489		probably benign	Het
Mnat1	A	G	12: 73,123,878	Y14C	probably damaging	Het
Mtdh	A	T	15: 34,083,135	T34S	possibly damaging	Het
Ncaph	T	C	2: 127,121,257	D352G	possibly damaging	Het
Olfr1014	T	C	2: 85,777,115	F177S	probably damaging	Het
Olfr1036	T	A	2: 86,075,510	Y257N	probably damaging	Het
Olfr1293-ps	C	A	2: 111,528,224	N321K	probably benign	Het
Olfr224	A	G	11: 58,566,518	Y276H	probably damaging	Het
Pcdhb13	T	A	18: 37,444,784	D738E	possibly damaging	Het
Pla2g4f	C	T	2: 120,300,499	R825Q	probably benign	Het
Pnliprp2	C	T	19: 58,775,145	L409F	possibly damaging	Het
Prlr	G	T	15: 10,319,195	C70F	probably damaging	Het
Ptpn14	C	T	1: 189,851,272	T772I	probably benign	Het
Ryr2	T	C	13: 11,785,080	Q927R	probably damaging	Het
Scarf1	A	G	11: 75,525,634	E634G	probably benign	Het
Slc39a14	A	T	14: 70,315,811	S158R	probably damaging	Het
Slc9c1	A	T	16: 45,544,831	T176S	probably benign	Het
Srsf10	T	C	4: 135,856,230	S2P	probably damaging	Het
Tcam1	T	A	11: 106,282,879	C50S	probably damaging	Het
Tdrd3	T	A	14: 87,505,787	H390Q	probably benign	Het
Tlk2	T	C	11: 105,253,359		probably null	Het
Tnc	G	C	4: 63,976,556	P1531R	probably damaging	Het
Tnfrsf1b	C	A	4: 145,246,757	Q15H	probably damaging	Het
Tnfrsf1b	T	G	4: 145,246,758	Q15P	possibly damaging	Het
Tssk4	A	T	14: 55,651,809	E264V	probably damaging	Het
Ttc37	T	G	13: 76,185,113		probably null	Het
Ugt3a2	G	A	15: 9,365,188	V296I	probably benign	Het
Usp5	C	G	6: 124,822,630	K318N	possibly damaging	Het
Vmn2r8	T	G	5: 108,799,263	E541A	probably benign	Het
Ybx1	A	T	4: 119,278,938		probably benign	Het
Zfp39	T	A	11: 58,891,231	Y235F	possibly damaging	Het
Zfp422	T	A	6: 116,626,943	K32*	probably null	Het
Zpbp2	T	A	11: 98,551,324		probably null	Het

Other mutations in Tcf7l2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00771:Tcf7l2	APN	19	55917421	missense	probably damaging	1.00
IGL01013:Tcf7l2	APN	19	55919627	splice site	probably benign
IGL02871:Tcf7l2	APN	19	55918997	missense	probably damaging	1.00
banned	UTSW	19	55931432	critical splice acceptor site	probably null
Notable	UTSW	19	55926740	missense	unknown
PIT4468001:Tcf7l2	UTSW	19	55742388	missense	probably damaging	1.00
R0927:Tcf7l2	UTSW	19	55918955	missense	probably damaging	1.00
R1078:Tcf7l2	UTSW	19	55743195	missense	probably benign	0.19
R4580:Tcf7l2	UTSW	19	55919036	missense	probably damaging	1.00
R4721:Tcf7l2	UTSW	19	55931454	missense	possibly damaging	0.89
R4814:Tcf7l2	UTSW	19	55924072	nonsense	probably null
R5222:Tcf7l2	UTSW	19	55898612	missense	probably benign
R5484:Tcf7l2	UTSW	19	55919508	splice site	probably null
R5808:Tcf7l2	UTSW	19	55908541	missense	probably damaging	1.00
R5914:Tcf7l2	UTSW	19	55898560	missense	probably benign	0.00
R6077:Tcf7l2	UTSW	19	55917436	nonsense	probably null
R6116:Tcf7l2	UTSW	19	55919014	missense	probably damaging	1.00
R6861:Tcf7l2	UTSW	19	55742523	missense	probably damaging	1.00
R6970:Tcf7l2	UTSW	19	55755048	missense	probably benign	0.44
R7009:Tcf7l2	UTSW	19	55894733	critical splice donor site	probably null
R7382:Tcf7l2	UTSW	19	55926740	missense	unknown
R7669:Tcf7l2	UTSW	19	55924543	nonsense	probably null
R7761:Tcf7l2	UTSW	19	55926036	missense	probably damaging	1.00
R7823:Tcf7l2	UTSW	19	55743089	missense	possibly damaging	0.73
R7952:Tcf7l2	UTSW	19	55898557	start codon destroyed	probably benign	0.00
R8753:Tcf7l2	UTSW	19	55931763	missense	possibly damaging	0.60
R9333:Tcf7l2	UTSW	19	55931496	nonsense	probably null
R9342:Tcf7l2	UTSW	19	55743085	missense	probably benign
R9395:Tcf7l2	UTSW	19	55931768	nonsense	probably null
R9610:Tcf7l2	UTSW	19	55910606	missense	probably null	1.00
R9611:Tcf7l2	UTSW	19	55910606	missense	probably null	1.00

Predicted Primers

PCR Primer
(F):5'- GGCAAATCAGAGTGGACCTG -3'
(R):5'- TTGGTCACCAGAGACAGAGG -3'

Sequencing Primer
(F):5'- TCAGAGTGGACCTGGGAGC -3'
(R):5'- TTCCAGCCAGCGAGTTGTG -3'

Genotyping

Genotyping is performed by amplifying the region containing the mutation using PCR, followed by sequencing of the amplified region to detect the mutation.

PCR Primers

R49570080_PCR_F: 5’- GGCAAATCAGAGTGGACCTG-3’

R49570080_PCR_R: 5’- TTGGTCACCAGAGACAGAGG-3’

Sequencing Primers

R49570080_SEQ_F: 5’- TCAGAGTGGACCTGGGAGC-3’ 

R49570080_SEQ_R: 5’- TTCCAGCCAGCGAGTTGTG-3’ 

PCR program

1) 94°C 2:00

2) 94°C 0:30

3) 55°C 0:30

4) 72°C 1:00

5) repeat steps (2-4) 40X

6) 72°C 10:00

7) 4°C hold

The following sequence of 602 nucleotides is amplified (Chr19: 55931243-55931844; NC_000085):

ggcaaatcag agtggacctg ggagcctcac agcccaccga agtcactgct tttaattgct

ccgtgacctc gggccatgac ttgcaggggg acatccctta ggtgacatca acttgccgtg

agcattagat aactctctcc cctggcgtct ttgcccttta ttcacagaca actctctccc

cctgtttcta ggagaaaaaa aaagtgcgtt cgctacatac aaggtgaagg cagctgcctc

agcccaccct cttcagatgg aagcttacta gactcgcctc ccccctcacc gcatctgcta

ggctcccctc cccaagacgc caagtcacag actgagcaga cccagccgct ctcgctgtcc

ctgaagcctg atcctctggc ccacctgtcc atgatgcctc cgccacccgc gctcctgttg

gccgaagctg cccacggcaa ggcctctgcc ctctgtccca atggggctct ggacctgcca

cctgccgctc tgcagccgtc catggtccct tcctcatcgc tcgcacaacc atcaacttct

tccttacatt cccacaactc gctggctgga acgcaacccc agcctctgtc tctggtgacc

Primer binding sites are underlined and the sequencing primer is highlighted; the mutated nucleotide is shown in red text (Chr. (+) = A>G).

Posted On

2016-04-27