Incidental Mutation 'R0006:Tpm3'
ID8184
Institutional Source Beutler Lab
Gene Symbol Tpm3
Ensembl Gene ENSMUSG00000027940
Gene Nametropomyosin 3, gamma
SynonymsskalphaTM.2, Trop-5, Tpm5, hTMnm, Tm5NM, gamma-TM, Tpm-5, hTM30nm
MMRRC Submission 041980-MU
Accession Numbers

Ncbi RefSeq: NM_022314.3, NM_001253738.1, NM_001253740.1; MGI:1890149

Is this an essential gene? Essential (E-score: 1.000) question?
Stock #R0006 (G1)
Quality Score
Status Validated
Chromosome3
Chromosomal Location90072649-90100902 bp(+) (GRCm38)
Type of Mutationsplice site
DNA Base Change (assembly) T to A at 90087661 bp
ZygosityHeterozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000114229 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000029549] [ENSMUST00000118566] [ENSMUST00000119158] [ENSMUST00000119570] [ENSMUST00000121503] [ENSMUST00000127955] [ENSMUST00000149432]
Predicted Effect probably benign
Transcript: ENSMUST00000029549
SMART Domains Protein: ENSMUSP00000029549
Gene: ENSMUSG00000027940

DomainStartEndE-ValueType
Pfam:Tropomyosin_1 4 117 3.9e-22 PFAM
Pfam:Tropomyosin 12 248 7.2e-93 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000118566
SMART Domains Protein: ENSMUSP00000113056
Gene: ENSMUSG00000027940

DomainStartEndE-ValueType
Pfam:Tropomyosin_1 3 117 2e-21 PFAM
Pfam:Tropomyosin 12 248 1.7e-100 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000119158
SMART Domains Protein: ENSMUSP00000113219
Gene: ENSMUSG00000027940

DomainStartEndE-ValueType
Pfam:Tropomyosin_1 4 117 1.7e-22 PFAM
Pfam:Tropomyosin 12 247 3.9e-96 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000119570
SMART Domains Protein: ENSMUSP00000113978
Gene: ENSMUSG00000027940

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 benign
Transcript: ENSMUST00000121503
SMART Domains Protein: ENSMUSP00000113578
Gene: ENSMUSG00000027940

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 noncoding transcript
Transcript: ENSMUST00000131354
Predicted Effect noncoding transcript
Transcript: ENSMUST00000133281
Predicted Effect noncoding transcript
Transcript: ENSMUST00000133361
Predicted Effect noncoding transcript
Transcript: ENSMUST00000136125
Predicted Effect noncoding transcript
Transcript: ENSMUST00000143281
Predicted Effect noncoding transcript
Transcript: ENSMUST00000147430
Predicted Effect noncoding transcript
Transcript: ENSMUST00000149115
Predicted Effect probably benign
Transcript: ENSMUST00000149432
SMART Domains Protein: ENSMUSP00000114229
Gene: ENSMUSG00000027940

DomainStartEndE-ValueType
Pfam:Tropomyosin 1 70 1.6e-28 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000149734
Predicted Effect noncoding transcript
Transcript: ENSMUST00000151798
Coding Region Coverage
  • 1x: 77.9%
  • 3x: 66.3%
  • 10x: 36.9%
  • 20x: 17.4%
Validation Efficiency 95% (74/78)
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: 26 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Appl2 A G 10: 83,602,898 F556L probably damaging Het
Atad2b T A 12: 4,942,030 S210T possibly damaging Het
Aurka A G 2: 172,359,753 probably null Het
Chd8 A G 14: 52,235,293 I351T possibly damaging Het
Chid1 T A 7: 141,496,426 probably benign Het
Dnase2b T A 3: 146,582,489 I284F probably damaging Het
Dst C T 1: 34,228,918 T5325I probably benign Het
Erbb3 A G 10: 128,573,410 probably null Het
Fancl A G 11: 26,469,695 N316S possibly damaging Het
Gabrd C A 4: 155,388,601 V72L probably damaging Het
Hephl1 T A 9: 15,076,764 T683S probably benign Het
Jazf1 A G 6: 52,894,086 probably benign Het
Kntc1 T A 5: 123,789,138 S1219T probably benign Het
L3mbtl1 A T 2: 162,964,569 Y460F possibly damaging Het
Map1b C T 13: 99,435,302 V304M probably damaging Het
Msantd4 A G 9: 4,384,099 E140G probably damaging Het
Myo16 A G 8: 10,475,988 K843E probably damaging Het
Rap1gds1 G T 3: 138,983,871 probably null Het
Rsph4a T C 10: 33,909,148 C148R probably damaging Het
Slc7a9 A T 7: 35,470,100 probably benign Het
Sptbn1 A G 11: 30,123,855 S1405P probably damaging Het
Tex35 T C 1: 157,099,744 K154E possibly damaging Het
Ubr4 T C 4: 139,431,649 F2438L probably benign Het
Wfdc8 T C 2: 164,599,064 D253G probably damaging Het
Zfp451 A T 1: 33,802,780 probably benign Het
Zfp687 A G 3: 95,011,456 I335T probably damaging 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
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
X0020:Tpm3 UTSW 3 90087574 critical splice donor site probably null
Protein Function and Prediction

Tropomyosins are components of the thin filaments of the sarcomere; TPM3 is expressed predominantly in slow, type 1 muscle fibers (1).  They function to mediate the effect of calcium on the actin-myosin interaction (1).  TPM3, along with TPM1 encode the alpha subunit of the muscle tropomyosin alpha-beta dimer; TPM2 encodes the beta subunit [reviewed in (2)]. A knockout mouse model determined that TPM3 is required for embryonic development and cell survival (3).

Background

Phenotype

OMIM #

Brief Description

Refs

CAP myopathy

609284

Congenital muscular dystrophy associated with cap structures on skeletal muscle biopsy; patients have slowly progressive muscle weakness and/or delayed motor development

(4;5)

Myopathy, congenital, with fiber-type disproportion

255310

Disorder in which there is relative hypotrophy of type 1 muscle fibers; patients often have muscle weakness and failure to thrive

(6)

Nemaline myopathy 1, autosomal dominant

609284

A form of congenital myopathy characterized by abnormal thread- or rod-like structures in muscle fibers on histologic examination; the clinical phenotype is highly variable, with differing age at onset and severity

(1;7;8)

 

An autosomal dominant mouse mimicked patients with nemaline myopathy in that they exhibited muscle weakness at 5-6 months of age as well as rods present in all muscles and hypertrophy of fast, glycolytic fibres (9).

 

Tpm3tm1Pgun/tm1Pgun; MGI:3040795

involves: 129X1/SvJ

Homozygous inactivation of this gene results in early embryonic death, prior to blastocyst formation (3).

References
Posted On2012-11-20
Science WriterAnne Murray