Mutagenetix > Incidental Mutation

Incidental Mutation 'R6861:Tcf7l2'

535571

Institutional Source

Beutler Lab

Gene Symbol

Tcf7l2

Ensembl Gene

ENSMUSG00000024985

Gene Name

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

Synonyms

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

MMRRC Submission

044962-MU

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R6861 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

55730252-55922086 bp(+) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to G at 55730955 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glycine at position 19 (D19G)

Ref Sequence

ENSEMBL: ENSMUSP00000118661 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000041717] [ENSMUST00000061496] [ENSMUST00000111649] [ENSMUST00000111651] [ENSMUST00000111652] [ENSMUST00000111653] [ENSMUST00000111654] [ENSMUST00000111656] [ENSMUST00000111657] [ENSMUST00000111658] [ENSMUST00000111659] [ENSMUST00000111662] [ENSMUST00000153888]

AlphaFold

no structure available at present

Predicted Effect

probably benign
Transcript: ENSMUST00000041717
AA Change: D61G

PolyPhen 2 Score 0.296 (Sensitivity: 0.91; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000042950
Gene: ENSMUSG00000024985
AA Change: D61G

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 benign
Transcript: ENSMUST00000061496
AA Change: D61G

PolyPhen 2 Score 0.017 (Sensitivity: 0.95; Specificity: 0.80)

SMART Domains

Protein: ENSMUSP00000050081
Gene: ENSMUSG00000024985
AA Change: D61G

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

possibly damaging
Transcript: ENSMUST00000111649
AA Change: D61G

PolyPhen 2 Score 0.829 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000107276
Gene: ENSMUSG00000024985
AA Change: D61G

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	236	2.5e-95	PFAM

Predicted Effect

probably damaging
Transcript: ENSMUST00000111651
AA Change: D61G

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

SMART Domains

Protein: ENSMUSP00000107278
Gene: ENSMUSG00000024985
AA Change: D61G

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	284	2.3e-94	PFAM

Predicted Effect

possibly damaging
Transcript: ENSMUST00000111652
AA Change: D61G

PolyPhen 2 Score 0.813 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000107279
Gene: ENSMUSG00000024985
AA Change: D61G

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	259	9.1e-93	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000111653
AA Change: D61G

PolyPhen 2 Score 0.337 (Sensitivity: 0.90; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000107280
Gene: ENSMUSG00000024985
AA Change: D61G

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	236	2.1e-95	PFAM
HMG	331	401	1.16e-22	SMART
low complexity region	407	415	N/A	INTRINSIC
low complexity region	439	452	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000111654
AA Change: D61G

PolyPhen 2 Score 0.813 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000107281
Gene: ENSMUSG00000024985
AA Change: D61G

Domain	Start	End	E-Value	Type
Pfam:CTNNB1_binding	1	259	4.2e-93	PFAM
HMG	345	415	1.16e-22	SMART
low complexity region	421	429	N/A	INTRINSIC
low complexity region	453	466	N/A	INTRINSIC

Predicted Effect

possibly damaging
Transcript: ENSMUST00000111656
AA Change: D61G

PolyPhen 2 Score 0.942 (Sensitivity: 0.80; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000107283
Gene: ENSMUSG00000024985
AA Change: D61G

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

possibly damaging
Transcript: ENSMUST00000111657
AA Change: D61G

PolyPhen 2 Score 0.829 (Sensitivity: 0.84; Specificity: 0.93)

SMART Domains

Protein: ENSMUSP00000107284
Gene: ENSMUSG00000024985
AA Change: D61G

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 benign
Transcript: ENSMUST00000111658
AA Change: D61G

PolyPhen 2 Score 0.102 (Sensitivity: 0.93; Specificity: 0.86)

SMART Domains

Protein: ENSMUSP00000107286
Gene: ENSMUSG00000024985
AA Change: D61G

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 benign
Transcript: ENSMUST00000111659
AA Change: D61G

PolyPhen 2 Score 0.035 (Sensitivity: 0.94; Specificity: 0.82)

SMART Domains

Protein: ENSMUSP00000107287
Gene: ENSMUSG00000024985
AA Change: D61G

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

possibly damaging
Transcript: ENSMUST00000111662
AA Change: D61G

PolyPhen 2 Score 0.901 (Sensitivity: 0.82; Specificity: 0.94)

SMART Domains

Protein: ENSMUSP00000107291
Gene: ENSMUSG00000024985
AA Change: D61G

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

SMART Domains

Protein: ENSMUSP00000123428
Gene: ENSMUSG00000024985
AA Change: D53G

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 damaging
Transcript: ENSMUST00000153888
AA Change: D19G

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)

SMART Domains

Protein: ENSMUSP00000118661
Gene: ENSMUSG00000024985
AA Change: D19G

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

Coding Region Coverage

1x: 100.0%
3x: 99.9%
10x: 99.6%
20x: 98.6%

Validation Efficiency

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: 86 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adamtsl4	G	A	3: 95,588,194 (GRCm39)	R598C	probably damaging	Het
Adra2a	T	C	19: 54,034,818 (GRCm39)	L58P	probably damaging	Het
Ajm1	C	CTCTA	2: 25,469,733 (GRCm39)		probably null	Het
Alox5ap	A	G	5: 149,201,927 (GRCm39)	D2G	probably damaging	Het
Arid1b	G	A	17: 5,377,961 (GRCm39)	V1238M	possibly damaging	Het
Bank1	A	G	3: 135,960,764 (GRCm39)	V31A	probably benign	Het
Bptf	G	A	11: 106,953,391 (GRCm39)	T2117M	probably damaging	Het
Cadps	G	A	14: 12,522,401 (GRCm38)	R588*	probably null	Het
Cavin4	A	G	4: 48,672,214 (GRCm39)	I220V	probably benign	Het
Cep192	G	A	18: 67,974,699 (GRCm39)	M1267I	probably benign	Het
Cers5	G	A	15: 99,670,244 (GRCm39)		probably benign	Het
Cfap65	A	T	1: 74,964,274 (GRCm39)	I558N	probably damaging	Het
Cfh	A	T	1: 140,028,621 (GRCm39)	S1025T	probably benign	Het
Cftr	A	G	6: 18,268,107 (GRCm39)	I689V	probably benign	Het
Cgrrf1	T	C	14: 47,069,785 (GRCm39)	I18T	probably damaging	Het
CK137956	A	G	4: 127,864,519 (GRCm39)	S37P	probably damaging	Het
Clca4a	T	C	3: 144,676,416 (GRCm39)	D88G	probably benign	Het
Col11a1	G	A	3: 113,961,141 (GRCm39)	G1166D	probably damaging	Het
Col24a1	G	A	3: 145,166,589 (GRCm39)	G1075S	probably damaging	Het
Crispld2	C	T	8: 120,752,852 (GRCm39)	T299M	probably damaging	Het
Cyb561a3	T	A	19: 10,562,701 (GRCm39)	Y114N	probably damaging	Het
Cyp3a57	T	A	5: 145,307,773 (GRCm39)	W147R	possibly damaging	Het
Dnah2	C	A	11: 69,346,789 (GRCm39)	R2599L	possibly damaging	Het
Dock1	T	A	7: 134,373,207 (GRCm39)	S525T	probably benign	Het
Drc7	T	G	8: 95,789,025 (GRCm39)		probably null	Het
Efhd2	G	T	4: 141,587,192 (GRCm39)		probably null	Het
Epb41l1	A	T	2: 156,367,142 (GRCm39)	E658D	probably benign	Het
Evi5	C	T	5: 107,896,184 (GRCm39)	S753N	probably benign	Het
Exoc3	A	T	13: 74,337,319 (GRCm39)	D427E	probably benign	Het
Fbxw9	A	G	8: 85,792,740 (GRCm39)	D363G	probably damaging	Het
Fcer2a	T	C	8: 3,732,910 (GRCm39)	Y277C	probably damaging	Het
Fstl5	A	T	3: 76,229,523 (GRCm39)	Y108F	probably damaging	Het
Gcn1	A	G	5: 115,749,108 (GRCm39)	D1880G	probably benign	Het
Gm4924	T	A	10: 82,214,948 (GRCm39)	Y915*	probably null	Het
Gpr139	T	A	7: 118,743,875 (GRCm39)	I237F	probably benign	Het
Hao2	A	G	3: 98,784,498 (GRCm39)	L289S	probably damaging	Het
Hexim1	A	G	11: 103,007,793 (GRCm39)	S16G	probably benign	Het
Hmgcs1	T	A	13: 120,161,535 (GRCm39)	M109K	probably damaging	Het
Hs3st4	T	A	7: 123,996,052 (GRCm39)	N239K	possibly damaging	Het
Hsd3b5	T	A	3: 98,529,328 (GRCm39)	N101Y	probably damaging	Het
Idh2	G	A	7: 79,747,966 (GRCm39)	P245S	probably damaging	Het
Irx3	A	G	8: 92,525,530 (GRCm39)		probably benign	Het
Lilra5	A	T	7: 4,244,931 (GRCm39)	D234V	probably benign	Het
Lrfn5	G	A	12: 61,886,476 (GRCm39)	S88N	probably damaging	Het
Lrp2	A	T	2: 69,343,721 (GRCm39)	S879R	possibly damaging	Het
Lsm11	A	G	11: 45,824,781 (GRCm39)	S249P	probably benign	Het
Ltbp1	C	T	17: 75,534,187 (GRCm39)	A543V	possibly damaging	Het
Mbd1	GTCTGCATCTGCGTCTTCGTCTGCATCTGCATCTGCGTCTTCGTCTGCATCTGCATCTGC	GTCTGCATCTGCGTCTTCGTCTGCATCTGCATCTGC	18: 74,406,645 (GRCm39)			Het
Mier2	C	T	10: 79,376,990 (GRCm39)		probably benign	Het
Mup6	G	C	4: 60,004,093 (GRCm39)	G70A	probably benign	Het
Neb	A	G	2: 52,085,732 (GRCm39)	L5258P	probably damaging	Het
Nlrc5	G	A	8: 95,247,857 (GRCm39)		probably benign	Het
Nr6a1	A	T	2: 38,630,597 (GRCm39)	F207I	possibly damaging	Het
Or2y1	A	T	11: 49,385,632 (GRCm39)	T91S	probably benign	Het
Or5k17	A	T	16: 58,746,867 (GRCm39)	D22E	probably benign	Het
Or8b43	T	C	9: 38,360,731 (GRCm39)	C188R	probably damaging	Het
Osbp2	A	G	11: 3,665,191 (GRCm39)	V51A	possibly damaging	Het
Papln	G	T	12: 83,821,723 (GRCm39)	C317F	probably damaging	Het
Pdcd7	T	C	9: 65,265,904 (GRCm39)	S454P	probably damaging	Het
Pde4a	C	T	9: 21,116,597 (GRCm39)	T473I	probably damaging	Het
Peg10	CC	CCCCATCAGGC	6: 4,756,350 (GRCm39)		probably benign	Het
Peg10	C	CCCATCAGGA	6: 4,756,351 (GRCm39)		probably benign	Het
Peg3	G	T	7: 6,714,385 (GRCm39)	S279*	probably null	Het
Rbl1	A	G	2: 156,994,887 (GRCm39)	Y929H	probably damaging	Het
Rsf1	G	GACGGCGGCA	7: 97,229,116 (GRCm39)		probably benign	Het
Sall3	C	A	18: 81,017,590 (GRCm39)	E113*	probably null	Het
Scn5a	A	C	9: 119,359,089 (GRCm39)	F653V	probably damaging	Het
Selenok	T	A	14: 29,692,005 (GRCm39)	N14K	possibly damaging	Het
Slc22a20	T	C	19: 6,021,838 (GRCm39)	T426A	probably benign	Het
Slc4a2	T	A	5: 24,640,007 (GRCm39)	S563T	probably damaging	Het
Sspo	T	A	6: 48,464,889 (GRCm39)	S3798T	probably benign	Het
Stag3	G	T	5: 138,302,969 (GRCm39)	R63L	possibly damaging	Het
Stard9	A	T	2: 120,535,667 (GRCm39)	M3975L	probably benign	Het
Syne2	C	A	12: 75,956,040 (GRCm39)	T582K	probably damaging	Het
Synj1	G	A	16: 90,760,768 (GRCm39)	Q748*	probably null	Het
Tas2r109	T	C	6: 132,957,048 (GRCm39)	D294G	probably benign	Het
Tbl1xr1	C	T	3: 22,245,603 (GRCm39)	T203M	possibly damaging	Het
Tbl1xr1	T	A	3: 22,245,703 (GRCm39)		probably null	Het
Tecta	A	G	9: 42,248,633 (GRCm39)	V1923A	possibly damaging	Het
Tg	T	A	15: 66,560,740 (GRCm39)	M1034K	probably benign	Het
Ttf2	T	C	3: 100,876,941 (GRCm39)	E8G	possibly damaging	Het
Vps13b	T	A	15: 35,576,541 (GRCm39)	V983E	probably damaging	Het
Vps35l	A	G	7: 118,342,898 (GRCm39)	H32R	probably damaging	Het
Vwa2	T	C	19: 56,890,025 (GRCm39)	V210A	probably benign	Het
Xkr6	T	A	14: 64,057,093 (GRCm39)	Y335N	probably benign	Het
Zfp97	A	G	17: 17,365,437 (GRCm39)	H312R	probably damaging	Het

Other mutations in Tcf7l2

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL00771:Tcf7l2	APN	19	55,905,853 (GRCm39)	missense	probably damaging	1.00
IGL01013:Tcf7l2	APN	19	55,908,059 (GRCm39)	splice site	probably benign
IGL02871:Tcf7l2	APN	19	55,907,429 (GRCm39)	missense	probably damaging	1.00
banned	UTSW	19	55,919,864 (GRCm39)	critical splice acceptor site	probably null
Notable	UTSW	19	55,915,172 (GRCm39)	missense	unknown
PIT4468001:Tcf7l2	UTSW	19	55,730,820 (GRCm39)	missense	probably damaging	1.00
R0927:Tcf7l2	UTSW	19	55,907,387 (GRCm39)	missense	probably damaging	1.00
R1078:Tcf7l2	UTSW	19	55,731,627 (GRCm39)	missense	probably benign	0.19
R4580:Tcf7l2	UTSW	19	55,907,468 (GRCm39)	missense	probably damaging	1.00
R4721:Tcf7l2	UTSW	19	55,919,886 (GRCm39)	missense	possibly damaging	0.89
R4814:Tcf7l2	UTSW	19	55,912,504 (GRCm39)	nonsense	probably null
R4957:Tcf7l2	UTSW	19	55,919,864 (GRCm39)	critical splice acceptor site	probably null
R5222:Tcf7l2	UTSW	19	55,887,044 (GRCm39)	missense	probably benign
R5484:Tcf7l2	UTSW	19	55,907,940 (GRCm39)	splice site	probably null
R5808:Tcf7l2	UTSW	19	55,896,973 (GRCm39)	missense	probably damaging	1.00
R5914:Tcf7l2	UTSW	19	55,886,992 (GRCm39)	missense	probably benign	0.00
R6077:Tcf7l2	UTSW	19	55,905,868 (GRCm39)	nonsense	probably null
R6116:Tcf7l2	UTSW	19	55,907,446 (GRCm39)	missense	probably damaging	1.00
R6970:Tcf7l2	UTSW	19	55,743,480 (GRCm39)	missense	probably benign	0.44
R7009:Tcf7l2	UTSW	19	55,883,165 (GRCm39)	critical splice donor site	probably null
R7382:Tcf7l2	UTSW	19	55,915,172 (GRCm39)	missense	unknown
R7669:Tcf7l2	UTSW	19	55,912,975 (GRCm39)	nonsense	probably null
R7761:Tcf7l2	UTSW	19	55,914,468 (GRCm39)	missense	probably damaging	1.00
R7823:Tcf7l2	UTSW	19	55,731,521 (GRCm39)	missense	possibly damaging	0.73
R7952:Tcf7l2	UTSW	19	55,886,989 (GRCm39)	start codon destroyed	probably benign	0.00
R8753:Tcf7l2	UTSW	19	55,920,195 (GRCm39)	missense	possibly damaging	0.60
R9333:Tcf7l2	UTSW	19	55,919,928 (GRCm39)	nonsense	probably null
R9342:Tcf7l2	UTSW	19	55,731,517 (GRCm39)	missense	probably benign
R9395:Tcf7l2	UTSW	19	55,920,200 (GRCm39)	nonsense	probably null
R9610:Tcf7l2	UTSW	19	55,899,038 (GRCm39)	missense	probably null	1.00
R9611:Tcf7l2	UTSW	19	55,899,038 (GRCm39)	missense	probably null	1.00

Predicted Primers

PCR Primer
(F):5'- AAAATTGCTGCTGCTGGTG -3'
(R):5'- TCGGAAACTTTCGGAGCGAG -3'

Sequencing Primer
(F):5'- AATGCCGCAGCTGAACG -3'
(R):5'- TTTCGGAGCGAGGCGGAG -3'

Posted On

2018-09-12