Mutagenetix > Incidental Mutation

Incidental Mutation 'R9664:Tardbp'

735603

Institutional Source

Beutler Lab

Gene Symbol

Tardbp

Ensembl Gene

ENSMUSG00000041459

Gene Name

TAR DNA binding protein

Synonyms

Tdp43, TDP-43, 1190002A23Rik

MMRRC Submission

Accession Numbers

Essential gene?

Essential (E-score: 1.000) question?

Stock #

R9664 (G1)

Quality Score

225.009

Status

Not validated

Chromosome

Chromosomal Location

148696839-148711476 bp(-) (GRCm39)

Type of Mutation

missense

DNA Base Change (assembly)

A to T at 148709751 bp (GRCm39)

Zygosity

Heterozygous

Amino Acid Change

Aspartic acid to Glutamic Acid at position 23 (D23E)

Ref Sequence

ENSEMBL: ENSMUSP00000081142 (fasta)

Gene Model

predicted gene model for transcript(s): [ENSMUST00000045180] [ENSMUST00000084125] [ENSMUST00000095719] [ENSMUST00000105699] [ENSMUST00000105700] [ENSMUST00000105702] [ENSMUST00000140897] [ENSMUST00000165113] [ENSMUST00000172073] [ENSMUST00000185673] [ENSMUST00000186947] [ENSMUST00000187939] [ENSMUST00000188134] [ENSMUST00000189048] [ENSMUST00000190552] [ENSMUST00000190696] [ENSMUST00000191450]

AlphaFold

Q921F2

PDB Structure

Crystal structure of mouse TDP-43 RRM2 domain in complex with DNA [X-RAY DIFFRACTION]

Predicted Effect

probably damaging
Transcript: ENSMUST00000045180
AA Change: D23E

PolyPhen 2 Score 0.973 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000038113
Gene: ENSMUSG00000041459
AA Change: D23E

Domain	Start	End	E-Value	Type
RRM	105	176	1.38e-17	SMART
RRM	192	258	7.03e-10	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000084125
AA Change: D23E

PolyPhen 2 Score 0.977 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000081142
Gene: ENSMUSG00000041459
AA Change: D23E

Domain	Start	End	E-Value	Type
RRM	105	176	1.38e-17	SMART
RRM	192	258	7.03e-10	SMART
low complexity region	273	316	N/A	INTRINSIC
low complexity region	321	329	N/A	INTRINSIC
low complexity region	342	358	N/A	INTRINSIC
low complexity region	368	380	N/A	INTRINSIC
low complexity region	386	404	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000095719
AA Change: D23E

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000093386
Gene: ENSMUSG00000041459
AA Change: D23E

Domain	Start	End	E-Value	Type
RRM	105	176	1.38e-17	SMART
RRM	192	258	7.03e-10	SMART
low complexity region	274	285	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000105699
AA Change: D23E

PolyPhen 2 Score 0.973 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000101324
Gene: ENSMUSG00000041459
AA Change: D23E

Domain	Start	End	E-Value	Type
RRM	105	176	1.38e-17	SMART
RRM	192	258	7.03e-10	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000105700
AA Change: D23E

PolyPhen 2 Score 0.973 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000101325
Gene: ENSMUSG00000041459
AA Change: D23E

Domain	Start	End	E-Value	Type
RRM	105	176	1.38e-17	SMART
RRM	192	258	7.03e-10	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000105702
AA Change: D23E

PolyPhen 2 Score 0.973 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000101327
Gene: ENSMUSG00000041459
AA Change: D23E

Domain	Start	End	E-Value	Type
RRM	105	176	1.38e-17	SMART
RRM	192	258	7.03e-10	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000140897

SMART Domains

Protein: ENSMUSP00000135135
Gene: ENSMUSG00000041459

Domain	Start	End	E-Value	Type
Blast:RRM_2	1	28	2e-13	BLAST
RRM	44	110	3e-12	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000165113
AA Change: D23E

PolyPhen 2 Score 0.973 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000129342
Gene: ENSMUSG00000041459
AA Change: D23E

Domain	Start	End	E-Value	Type
RRM	105	176	1.38e-17	SMART
RRM	192	258	7.03e-10	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000172073
AA Change: D23E

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000130963
Gene: ENSMUSG00000041459
AA Change: D23E

Domain	Start	End	E-Value	Type
RRM	105	176	1.38e-17	SMART
RRM	192	258	7.03e-10	SMART
low complexity region	274	285	N/A	INTRINSIC

Predicted Effect

probably damaging
Transcript: ENSMUST00000185673
AA Change: D23E

PolyPhen 2 Score 0.977 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000141010
Gene: ENSMUSG00000041459
AA Change: D23E

Domain	Start	End	E-Value	Type
Pfam:RRM_1	106	149	3e-12	PFAM
Pfam:RRM_6	106	149	1.3e-6	PFAM

Predicted Effect

probably benign
Transcript: ENSMUST00000185824

Predicted Effect

probably damaging
Transcript: ENSMUST00000186947
AA Change: D23E

PolyPhen 2 Score 0.990 (Sensitivity: 0.72; Specificity: 0.97)

SMART Domains

Protein: ENSMUSP00000140529
Gene: ENSMUSG00000041459
AA Change: D23E

Domain	Start	End	E-Value	Type
RRM	105	176	5.8e-20	SMART
low complexity region	215	243	N/A	INTRINSIC

Predicted Effect

probably benign
Transcript: ENSMUST00000187939

SMART Domains

Protein: ENSMUSP00000140928
Gene: ENSMUSG00000041459

Domain	Start	End	E-Value	Type
RRM	18	84	3e-12	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000188134
AA Change: D23E

PolyPhen 2 Score 0.973 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000139476
Gene: ENSMUSG00000041459
AA Change: D23E

Domain	Start	End	E-Value	Type
RRM	105	176	1.38e-17	SMART
RRM	192	258	7.03e-10	SMART

Predicted Effect

probably damaging
Transcript: ENSMUST00000189048
AA Change: D23E

PolyPhen 2 Score 0.973 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000140364
Gene: ENSMUSG00000041459
AA Change: D23E

Domain	Start	End	E-Value	Type
RRM	105	176	1.38e-17	SMART
RRM	192	258	7.03e-10	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000190552

SMART Domains

Protein: ENSMUSP00000141052
Gene: ENSMUSG00000041459

Domain	Start	End	E-Value	Type
RRM_2	1	56	6.1e-4	SMART
RRM	72	138	3e-12	SMART

Predicted Effect

probably benign
Transcript: ENSMUST00000190696
AA Change: D23E

PolyPhen 2 Score 0.298 (Sensitivity: 0.91; Specificity: 0.89)

SMART Domains

Protein: ENSMUSP00000139637
Gene: ENSMUSG00000041459
AA Change: D23E

Domain	Start	End	E-Value	Type
Blast:RRM_2	55	79	8e-11	BLAST

Predicted Effect

probably benign
Transcript: ENSMUST00000191378

Predicted Effect

probably damaging
Transcript: ENSMUST00000191450
AA Change: D23E

PolyPhen 2 Score 0.973 (Sensitivity: 0.76; Specificity: 0.96)

SMART Domains

Protein: ENSMUSP00000140832
Gene: ENSMUSG00000041459
AA Change: D23E

Domain	Start	End	E-Value	Type
RRM	105	176	5.8e-20	SMART
RRM	192	258	3e-12	SMART

Coding Region Coverage

1x: 99.8%
3x: 99.7%
10x: 99.2%
20x: 98.2%

Validation Efficiency

MGI Phenotype

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator Tat is dependent on an RNA regulatory element (TAR) located downstream of the transcription initiation site. The protein encoded by this gene is a transcriptional repressor that binds to chromosomally integrated TAR DNA and represses HIV-1 transcription. In addition, this protein regulates alternate splicing of the CFTR gene. A similar pseudogene is present on chromosome 20. [provided by RefSeq, Jul 2008]
PHENOTYPE: Homozygous deficient mice display embryonic lethality before somite formation with impaired inner cell mass proliferation. [provided by MGI curators]

Allele List at MGI

Other mutations in this stock

Total: 99 list
Gene	Ref	Var	Chr/Loc	Mutation	Predicted Effect	Zygosity
Adck5	G	A	15: 76,478,383 (GRCm39)	D277N	probably damaging	Het
Adgrv1	A	T	13: 81,670,288 (GRCm39)	S2353T	probably benign	Het
Adgrv1	A	T	13: 81,743,371 (GRCm39)	N43K	probably damaging	Het
Adnp2	A	G	18: 80,185,937 (GRCm39)	I12T	probably damaging	Het
Ahnak2	A	G	12: 112,741,363 (GRCm39)	L903P	probably damaging	Het
Ankhd1	T	G	18: 36,780,878 (GRCm39)	S1977A	probably benign	Het
Ap1m2	T	C	9: 21,216,983 (GRCm39)	M118V	probably benign	Het
Ap3d1	T	C	10: 80,548,639 (GRCm39)	K846R	possibly damaging	Het
Aqr	C	A	2: 113,971,396 (GRCm39)	E480*	probably null	Het
Arl6	G	T	16: 59,434,199 (GRCm39)	Q182K	probably benign	Het
Arpc2	A	G	1: 74,294,034 (GRCm39)	K106E	probably benign	Het
Atp8a1	A	C	5: 67,889,524 (GRCm39)	F599V		Het
B3galt5	A	T	16: 96,117,203 (GRCm39)	I279F	probably damaging	Het
Calcoco2	G	T	11: 95,991,104 (GRCm39)	A211D	unknown	Het
Ccdc33	T	C	9: 57,993,855 (GRCm39)	E342G	possibly damaging	Het
Ccdc88a	C	A	11: 29,405,484 (GRCm39)	Q386K	probably benign	Het
Cdh20	A	G	1: 104,862,065 (GRCm39)	K82E	probably benign	Het
Clca3a2	A	T	3: 144,503,575 (GRCm39)	Y792N	probably damaging	Het
Col6a6	T	C	9: 105,658,254 (GRCm39)	I653V	probably benign	Het
Col7a1	C	T	9: 108,812,649 (GRCm39)	R2826W	unknown	Het
D6Ertd527e	A	G	6: 87,088,908 (GRCm39)	N357S	unknown	Het
Dmgdh	T	A	13: 93,857,123 (GRCm39)	N742K	probably benign	Het
Dnai3	T	C	3: 145,748,594 (GRCm39)	N840S	probably benign	Het
Dnajc6	A	G	4: 101,475,821 (GRCm39)	N565D	probably benign	Het
Doc2g	A	G	19: 4,054,390 (GRCm39)	Y155C	probably damaging	Het
Dot1l	G	A	10: 80,624,361 (GRCm39)	G943D	probably damaging	Het
Dst	T	C	1: 34,220,736 (GRCm39)	V2180A	probably benign	Het
Eftud2	A	C	11: 102,759,422 (GRCm39)	Y160*	probably null	Het
Ehd1	A	T	19: 6,331,262 (GRCm39)	Q140L	probably benign	Het
Etv3	T	C	3: 87,443,172 (GRCm39)	V252A	probably benign	Het
F11	A	T	8: 45,694,566 (GRCm39)	C598*	probably null	Het
Fancm	T	A	12: 65,137,758 (GRCm39)	N316K	probably benign	Het
Flnc	T	C	6: 29,457,214 (GRCm39)	V2372A	probably damaging	Het
Fry	A	G	5: 150,282,488 (GRCm39)	R338G	probably damaging	Het
Gfra3	T	C	18: 34,837,591 (GRCm39)	T136A	probably benign	Het
Golga7b	T	C	19: 42,255,462 (GRCm39)	V113A	possibly damaging	Het
Gpn3	G	T	5: 122,520,306 (GRCm39)	V102L		Het
Herc2	A	G	7: 55,820,338 (GRCm39)	N2859S	possibly damaging	Het
Hpd	A	T	5: 123,318,948 (GRCm39)		probably null	Het
Hspg2	C	T	4: 137,266,887 (GRCm39)	T1964I	probably benign	Het
Hydin	A	T	8: 111,220,965 (GRCm39)	T1454S	probably benign	Het
Irgm2	A	T	11: 58,110,872 (GRCm39)	T188S	possibly damaging	Het
Jak3	A	G	8: 72,131,366 (GRCm39)	D77G	probably damaging	Het
Kcnj4	G	T	15: 79,369,220 (GRCm39)	F253L	possibly damaging	Het
Kidins220	T	A	12: 25,106,895 (GRCm39)	D1358E	probably benign	Het
Klf1	C	A	8: 85,630,061 (GRCm39)	C295*	probably null	Het
Kmt2a	C	T	9: 44,760,102 (GRCm39)	W582*	probably null	Het
Lrig2	A	G	3: 104,371,556 (GRCm39)	C716R	probably damaging	Het
Lrp1b	C	T	2: 40,765,004 (GRCm39)	D2941N		Het
Lrpprc	A	T	17: 85,020,262 (GRCm39)	V1141E	probably damaging	Het
Mrgprx1	C	T	7: 47,671,273 (GRCm39)	G158D	probably benign	Het
Muc5b	C	A	7: 141,409,279 (GRCm39)	A1121D	unknown	Het
Nf1	G	T	11: 79,334,733 (GRCm39)	V852L	probably damaging	Het
Nlrp5	A	G	7: 23,118,286 (GRCm39)	E670G	probably benign	Het
Notch4	A	G	17: 34,784,601 (GRCm39)	T101A	probably benign	Het
Or10a49	T	C	7: 108,467,563 (GRCm39)	Y266C	probably damaging	Het
Or2t35	T	A	14: 14,407,963 (GRCm38)	I245K	probably benign	Het
Or5b123	G	A	19: 13,597,365 (GRCm39)	V237I	probably benign	Het
P2rx2	T	C	5: 110,488,172 (GRCm39)	T461A	probably benign	Het
Pank1	G	A	19: 34,799,194 (GRCm39)	T419I	probably damaging	Het
Patz1	T	C	11: 3,244,562 (GRCm39)	V481A	unknown	Het
Pdlim5	A	G	3: 142,018,058 (GRCm39)	L179P	probably benign	Het
Pik3ap1	A	T	19: 41,296,967 (GRCm39)	V461D	probably damaging	Het
Polq	T	C	16: 36,848,176 (GRCm39)	V261A	probably damaging	Het
Ppm1a	G	A	12: 72,837,451 (GRCm39)	V333M	possibly damaging	Het
R3hcc1l	T	C	19: 42,552,671 (GRCm39)	L556P	probably benign	Het
Rabggta	G	A	14: 55,956,375 (GRCm39)	Q365*	probably null	Het
Ranbp9	T	C	13: 43,578,519 (GRCm39)	T185A	probably benign	Het
Rd3l	T	G	12: 111,945,913 (GRCm39)	N189H	probably damaging	Het
Rnf17	A	G	14: 56,722,636 (GRCm39)	T1066A	probably damaging	Het
Rnf213	G	A	11: 119,332,794 (GRCm39)	A2669T		Het
Ros1	T	A	10: 51,996,931 (GRCm39)	H1268L	probably benign	Het
Rps6ka4	G	T	19: 6,809,354 (GRCm39)	S433R	possibly damaging	Het
Ryr1	A	G	7: 28,759,092 (GRCm39)	L3362P	probably damaging	Het
Setd1b	A	T	5: 123,298,046 (GRCm39)	T1361S	unknown	Het
Setd2	T	C	9: 110,377,570 (GRCm39)	S462P	probably damaging	Het
Sgsm3	A	T	15: 80,890,935 (GRCm39)	Q132L	probably benign	Het
Slx1b	C	A	7: 126,291,698 (GRCm39)	R122L	probably damaging	Het
Sorbs2	A	T	8: 46,276,788 (GRCm39)	T1167S	probably benign	Het
Spdya	A	C	17: 71,869,513 (GRCm39)	T103P	probably damaging	Het
Stfa2	A	G	16: 36,228,638 (GRCm39)	S20P	probably benign	Het
Sulf1	A	G	1: 12,891,026 (GRCm39)	T400A	probably benign	Het
Tekt2	C	T	4: 126,217,444 (GRCm39)	R207H	probably damaging	Het
Tgm1	C	T	14: 55,948,441 (GRCm39)	D237N	probably benign	Het
Tgs1	T	A	4: 3,585,964 (GRCm39)	N280K	probably benign	Het
Tmem198	A	T	1: 75,459,272 (GRCm39)	I76F	possibly damaging	Het
Trpv2	A	T	11: 62,475,385 (GRCm39)	Y266F	probably damaging	Het
Ttn	C	T	2: 76,569,845 (GRCm39)	G27016E	probably damaging	Het
Ttn	T	C	2: 76,781,824 (GRCm39)	E1074G	unknown	Het
Unc5b	A	T	10: 60,613,322 (GRCm39)	W305R	probably damaging	Het
Usp38	A	G	8: 81,741,164 (GRCm39)		probably benign	Het
Vmn1r79	A	G	7: 11,910,582 (GRCm39)	T155A	probably benign	Het
Vwce	G	A	19: 10,615,481 (GRCm39)	V121I	probably benign	Het
Wdr91	A	T	6: 34,865,961 (GRCm39)	D530E	probably benign	Het
Wnt4	A	G	4: 137,023,929 (GRCm39)	T299A	probably benign	Het
Yeats2	T	A	16: 20,047,491 (GRCm39)	Y1284*	probably null	Het
Zfp113	A	T	5: 138,148,888 (GRCm39)	Y85*	probably null	Het
Zfp184	A	G	13: 22,144,096 (GRCm39)	T601A	probably benign	Het
Zfp655	A	G	5: 145,180,442 (GRCm39)	E100G	probably damaging	Het

Other mutations in Tardbp

Allele	Source	Chr	Coord	Type	Predicted Effect	PPH Score
IGL01472:Tardbp	APN	4	148,706,521 (GRCm39)	missense	probably benign	0.03
IGL02569:Tardbp	APN	4	148,703,639 (GRCm39)	critical splice donor site	probably null
R4428:Tardbp	UTSW	4	148,709,659 (GRCm39)	missense	possibly damaging	0.88
R4690:Tardbp	UTSW	4	148,697,078 (GRCm39)	makesense	probably null
R4824:Tardbp	UTSW	4	148,702,050 (GRCm39)	missense	probably benign	0.33
R4925:Tardbp	UTSW	4	148,703,108 (GRCm39)	missense	probably benign	0.11
R5057:Tardbp	UTSW	4	148,703,813 (GRCm39)	critical splice acceptor site	probably null
R5137:Tardbp	UTSW	4	148,706,494 (GRCm39)	missense	possibly damaging	0.77
R5488:Tardbp	UTSW	4	148,703,097 (GRCm39)	missense	probably benign	0.03
R5833:Tardbp	UTSW	4	148,702,117 (GRCm39)	missense	probably damaging	1.00
R8164:Tardbp	UTSW	4	148,703,060 (GRCm39)	missense	probably benign	0.00
R8862:Tardbp	UTSW	4	148,702,755 (GRCm39)	missense	possibly damaging	0.73
R8905:Tardbp	UTSW	4	148,705,093 (GRCm39)	missense	probably benign	0.01

Predicted Primers

PCR Primer
(F):5'- GTCTAACCATGGCCAGCAATAC -3'
(R):5'- GCAGGAATCTTTTCAGGAAGTGGG -3'

Sequencing Primer
(F):5'- CCAAAATGATTAACAAACCTTTGGG -3'
(R):5'- TCTTTTCAGGAAGTGGGAATAAAGTG -3'

Posted On

2022-11-14