Incidental Mutation 'R8701:Tpm3'
ID 669042
Institutional Source Beutler Lab
Gene Symbol Tpm3
Ensembl Gene ENSMUSG00000027940
Gene Name tropomyosin 3, gamma
Synonyms skalphaTM.2, Trop-5, Tpm5, hTMnm, Tm5NM, gamma-TM, Tpm-5, hTM30nm
MMRRC Submission
Accession Numbers

Ncbi RefSeq: NM_022314.3, NM_001253738.1, NM_001253740.1; MGI:1890149
Essential gene? Essential (E-score: 1.000) question?
Stock # R8701 (G1)
Quality Score 225.009
Status Not validated
Chromosome 3
Chromosomal Location 90072649-90100902 bp(+) (GRCm38)
Type of Mutation missense
DNA Base Change (assembly) C to T at 90087680 bp (GRCm38)
Zygosity Heterozygous
Amino Acid Change Arginine to Cysteine at position 168 (R168C)
Ref Sequence ENSEMBL: ENSMUSP00000113978 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000029549] [ENSMUST00000118566] [ENSMUST00000119158] [ENSMUST00000119570] [ENSMUST00000121503] [ENSMUST00000127955] [ENSMUST00000149432]
AlphaFold no structure available at present
Predicted Effect probably benign
Transcript: ENSMUST00000029549
AA Change: R131C

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000029549
Gene: ENSMUSG00000027940
AA Change: R131C

DomainStartEndE-ValueType
Pfam:Tropomyosin_1 4 117 3.9e-22 PFAM
Pfam:Tropomyosin 12 248 7.2e-93 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000118566
AA Change: R131C

PolyPhen 2 Score 0.998 (Sensitivity: 0.27; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000113056
Gene: ENSMUSG00000027940
AA Change: R131C

DomainStartEndE-ValueType
Pfam:Tropomyosin_1 3 117 2e-21 PFAM
Pfam:Tropomyosin 12 248 1.7e-100 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000119158
AA Change: R131C

PolyPhen 2 Score 0.823 (Sensitivity: 0.84; Specificity: 0.93)
SMART Domains Protein: ENSMUSP00000113219
Gene: ENSMUSG00000027940
AA Change: R131C

DomainStartEndE-ValueType
Pfam:Tropomyosin_1 4 117 1.7e-22 PFAM
Pfam:Tropomyosin 12 247 3.9e-96 PFAM
Predicted Effect possibly damaging
Transcript: ENSMUST00000119570
AA Change: R168C

PolyPhen 2 Score 0.675 (Sensitivity: 0.86; Specificity: 0.92)
SMART Domains Protein: ENSMUSP00000113978
Gene: ENSMUSG00000027940
AA Change: R168C

DomainStartEndE-ValueType
Pfam:Tropomyosin_1 8 154 4.2e-35 PFAM
Pfam:CLZ 10 75 1.2e-9 PFAM
Pfam:Tropomyosin 49 285 3.7e-91 PFAM
Predicted Effect probably damaging
Transcript: ENSMUST00000121503
AA Change: R167C

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000113578
Gene: ENSMUSG00000027940
AA Change: R167C

DomainStartEndE-ValueType
Pfam:Tropomyosin_1 7 153 1.3e-36 PFAM
Pfam:Tropomyosin 48 284 4.7e-103 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000127955
Predicted Effect probably damaging
Transcript: ENSMUST00000149432
AA Change: R41C

PolyPhen 2 Score 0.996 (Sensitivity: 0.55; Specificity: 0.98)
SMART Domains Protein: ENSMUSP00000114229
Gene: ENSMUSG00000027940
AA Change: R41C

DomainStartEndE-ValueType
Pfam:Tropomyosin 1 70 1.6e-28 PFAM
Coding Region Coverage
  • 1x: 100.0%
  • 3x: 99.9%
  • 10x: 99.7%
  • 20x: 98.8%
Validation Efficiency
MGI Phenotype Strain: 3040795
Lethality: E1-E3
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a member of the tropomyosin family of actin-binding proteins. Tropomyosins are dimers of coiled-coil proteins that provide stability to actin filaments and regulate access of other actin-binding proteins. Mutations in this gene result in autosomal dominant nemaline myopathy and other muscle disorders. This locus is involved in translocations with other loci, including anaplastic lymphoma receptor tyrosine kinase (ALK) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), which result in the formation of fusion proteins that act as oncogenes. There are numerous pseudogenes for this gene on different chromosomes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
PHENOTYPE: Homozygous inactivation of this gene results in early embryonic death, prior to blastocyst formation. Mice homozygous for a targeted allele lacking exon 9 exhibit dysmorphic T-tubules and contraction in skeletal muscles. [provided by MGI curators]
Allele List at MGI

All alleles(76) : Targeted(5) Gene trapped(71)
Other mutations in this stock
Total: 65 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
4931408C20Rik A T 1: 26,685,445 V218D probably benign Het
Abcc4 T C 14: 118,599,373 I659V probably benign Het
Adamtsl4 T A 3: 95,684,966 D24V possibly damaging Het
Agtr1b A T 3: 20,316,092 F117I probably damaging Het
Aldh3b2 A G 19: 3,978,448 E116G probably damaging Het
Alox5 T A 6: 116,413,826 I455F possibly damaging Het
Arnt C T 3: 95,493,765 S675F possibly damaging Het
C330027C09Rik T A 16: 49,007,141 Y456* probably null Het
Camkv A G 9: 107,948,041 T414A possibly damaging Het
Cd209c C T 8: 3,945,892 R6H probably benign Het
Cnr1 A G 4: 33,944,739 I376V probably benign Het
Cyp2j12 T A 4: 96,121,573 K183M possibly damaging Het
Dact3 G T 7: 16,885,276 R232L probably damaging Het
Dlg5 G A 14: 24,176,700 T378M probably benign Het
Dnah10 T A 5: 124,726,847 D79E probably benign Het
Dsc1 A T 18: 20,107,682 Y195* probably null Het
Elovl1 A T 4: 118,430,510 M1L probably benign Het
Fam107a A G 14: 8,298,755 F124L probably damaging Het
Fam219a A G 4: 41,520,283 M155T probably damaging Het
Gm28308 C G 6: 52,163,450 probably benign Het
Gpr153 C T 4: 152,279,101 probably benign Het
Gtf2ird2 T A 5: 134,216,235 I445N probably damaging Het
Gzmb A T 14: 56,260,360 V141E probably benign Het
Hmcn1 A T 1: 150,755,257 M930K probably benign Het
Hunk T A 16: 90,386,610 F52Y probably damaging Het
Il18rap A G 1: 40,539,341 E304G probably benign Het
Klk14 A G 7: 43,694,142 S133G possibly damaging Het
Man2b1 T C 8: 85,095,153 S695P probably damaging Het
Mccc1 A T 3: 35,995,784 D86E probably benign Het
Mcu T A 10: 59,467,653 I121F probably damaging Het
Mlxipl T C 5: 135,107,191 F90S possibly damaging Het
Muc2 A G 7: 141,695,607 D536G probably damaging Het
Naa11 T C 5: 97,391,958 S114G possibly damaging Het
Ncaph T C 2: 127,106,138 K676E probably benign Het
Neurl2 C T 2: 164,833,134 D103N probably benign Het
Nup210l T C 3: 90,122,814 M278T probably benign Het
Olfr1192-ps1 A G 2: 88,652,487 I112V possibly damaging Het
Olfr550 A T 7: 102,578,692 M66L possibly damaging Het
Olfr897-ps1 A T 9: 38,309,438 L214F unknown Het
Olfr967 A T 9: 39,750,914 H176L probably damaging Het
Olfr981 A G 9: 40,022,519 N42S probably damaging Het
Pcdh20 A T 14: 88,468,413 Y484N possibly damaging Het
Pkhd1l1 A G 15: 44,574,683 Y3598C probably damaging Het
Plcg2 T A 8: 117,581,677 L336Q probably damaging Het
Ppp1r8 T C 4: 132,830,642 D207G possibly damaging Het
Prdm13 C T 4: 21,678,615 C625Y probably damaging Het
Ptcd3 T C 6: 71,885,511 D480G possibly damaging Het
Rbm39 T A 2: 156,161,587 K291M probably damaging Het
Repin1 G T 6: 48,597,345 E403* probably null Het
Rnf220 T C 4: 117,489,993 H74R probably damaging Het
Sp6 A T 11: 97,022,264 T268S probably damaging Het
Sphk2 A T 7: 45,710,825 V585E probably damaging Het
Syne1 G A 10: 5,205,026 Q5638* probably null Het
Tas1r3 C T 4: 155,861,046 V573I probably benign Het
Tdrd1 T C 19: 56,851,484 S659P possibly damaging Het
Tead4 T A 6: 128,242,566 K237N probably damaging Het
Tex24 T A 8: 27,345,124 C227S probably benign Het
Tom1 A T 8: 75,052,168 T174S probably benign Het
Trpv3 A G 11: 73,278,936 E111G possibly damaging Het
Unc80 A G 1: 66,638,032 D2040G possibly damaging Het
Usp47 A G 7: 112,093,195 T955A probably damaging Het
Vmn2r11 G A 5: 109,047,690 A590V probably damaging Het
Wisp2 G T 2: 163,828,866 G98W probably damaging Het
Zfp112 A G 7: 24,125,740 R382G probably damaging Het
Zfp606 T A 7: 12,481,098 D84E unknown Het
Other mutations in Tpm3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00481:Tpm3 APN 3 90087717 missense probably damaging 0.99
IGL00949:Tpm3 APN 3 90089858 missense probably damaging 1.00
IGL01955:Tpm3 APN 3 90088435 missense probably benign 0.00
IGL01970:Tpm3 APN 3 90089828 missense probably damaging 1.00
IGL02605:Tpm3 APN 3 90088446 missense probably benign 0.13
IGL03352:Tpm3 APN 3 90087745 critical splice donor site probably null
IGL03375:Tpm3 APN 3 90073772 missense possibly damaging 0.83
P0045:Tpm3 UTSW 3 90091093 critical splice donor site probably null
R0006:Tpm3 UTSW 3 90087661 splice site probably benign
R0006:Tpm3 UTSW 3 90087661 splice site probably benign
R0024:Tpm3 UTSW 3 90087449 splice site probably null
R0086:Tpm3 UTSW 3 90090092 unclassified probably benign
R1487:Tpm3 UTSW 3 90090082 splice site probably null
R5235:Tpm3 UTSW 3 90086495 missense probably damaging 1.00
R6639:Tpm3 UTSW 3 90079802 missense probably damaging 0.99
R7089:Tpm3 UTSW 3 90072722 start gained probably benign
R7212:Tpm3 UTSW 3 90091054 missense probably benign
R7867:Tpm3 UTSW 3 90086468 missense probably damaging 1.00
R8322:Tpm3 UTSW 3 90073704 intron probably benign
R9167:Tpm3 UTSW 3 90087517 missense probably benign 0.13
X0020:Tpm3 UTSW 3 90087574 critical splice donor site probably null
Predicted Primers PCR Primer
(F):5'- AGGTGATTGAAAATCGGGCTC -3'
(R):5'- AGCCCAAAGCCATTCTTGG -3'

Sequencing Primer
(F):5'- TTGAAAATCGGGCTCTAAAAGATG -3'
(R):5'- CCATTCTTGGAGGCTAAAAGC -3'
Posted On 2021-04-30