Incidental Mutation '2107:Tmod4'
ID145
Institutional Source Beutler Lab
Gene Symbol Tmod4
Ensembl Gene ENSMUSG00000005628
Gene Nametropomodulin 4
SynonymsMTMOD, skeletal tropomodulin, Sk-Tmod
Accession Numbers
Is this an essential gene? Probably non essential (E-score: 0.228) question?
Stock #2107 of strain triaka
Quality Score
Status Validated
Chromosome3
Chromosomal Location95124476-95129209 bp(+) (GRCm38)
Type of Mutationunclassified
DNA Base Change (assembly) G to A at 95130168 bp
ZygosityHomozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000005769 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000005769] [ENSMUST00000066386] [ENSMUST00000107227] [ENSMUST00000131597] [ENSMUST00000172572] [ENSMUST00000173462]
Predicted Effect probably benign
Transcript: ENSMUST00000005769
SMART Domains Protein: ENSMUSP00000005769
Gene: ENSMUSG00000005628

DomainStartEndE-ValueType
Pfam:Tropomodulin 4 143 2.7e-62 PFAM
PDB:1IO0|A 160 343 6e-77 PDB
SCOP:d1a4ya_ 184 289 4e-4 SMART
Predicted Effect probably null
Transcript: ENSMUST00000066386
SMART Domains Protein: ENSMUSP00000067811
Gene: ENSMUSG00000053769

DomainStartEndE-ValueType
low complexity region 10 19 N/A INTRINSIC
LysM 41 85 2.58e-7 SMART
low complexity region 100 108 N/A INTRINSIC
low complexity region 117 132 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000107227
SMART Domains Protein: ENSMUSP00000102846
Gene: ENSMUSG00000005628

DomainStartEndE-ValueType
Pfam:Tropomodulin 1 144 4.4e-72 PFAM
PDB:1IO0|A 160 343 6e-77 PDB
SCOP:d1a4ya_ 184 289 4e-4 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000130545
Predicted Effect probably benign
Transcript: ENSMUST00000131597
SMART Domains Protein: ENSMUSP00000116341
Gene: ENSMUSG00000005628

DomainStartEndE-ValueType
Pfam:Tropomodulin 1 144 1.5e-72 PFAM
Predicted Effect noncoding transcript
Transcript: ENSMUST00000135867
Predicted Effect noncoding transcript
Transcript: ENSMUST00000149898
Predicted Effect probably benign
Transcript: ENSMUST00000172572
SMART Domains Protein: ENSMUSP00000134337
Gene: ENSMUSG00000092607

DomainStartEndE-ValueType
Pfam:zf-SCNM1 44 70 7.6e-19 PFAM
low complexity region 133 148 N/A INTRINSIC
low complexity region 172 179 N/A INTRINSIC
Predicted Effect probably benign
Transcript: ENSMUST00000173462
SMART Domains Protein: ENSMUSP00000133769
Gene: ENSMUSG00000092607

DomainStartEndE-ValueType
Blast:ZnF_C2H2 42 68 2e-7 BLAST
Predicted Effect noncoding transcript
Transcript: ENSMUST00000173527
Predicted Effect noncoding transcript
Transcript: ENSMUST00000174508
Predicted Effect noncoding transcript
Transcript: ENSMUST00000174835
Predicted Effect noncoding transcript
Transcript: ENSMUST00000174859
Predicted Effect noncoding transcript
Transcript: ENSMUST00000196728
Predicted Effect noncoding transcript
Transcript: ENSMUST00000199730
Meta Mutation Damage Score 0.634 question?
Coding Region Coverage
  • 1x: 86.3%
  • 3x: 63.7%
Validation Efficiency 80% (79/99)
MGI Phenotype PHENOTYPE: Mice homozygous for a knock-out allele are viable, fertile and exhibit no overt myopathy, with normal thin filament lengths, myofibril organization, and skeletal muscle contractile function. [provided by MGI curators]
Allele List at MGI
Other mutations in this stock
Total: 6 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Afmid T A 11: 117,835,561 N206K probably damaging Homo
Fam184a T C 10: 53,641,057 E374G probably damaging Homo
Mypn C T 10: 63,203,751 probably benign Homo
Nme7 T A 1: 164,345,353 I211N possibly damaging Het
Wfs1 C T 5: 36,967,273 R758H probably damaging Het
Zfp112 T C 7: 24,126,841 C749R probably damaging Het
Other mutations in Tmod4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00851:Tmod4 APN 3 95125580 missense probably damaging 1.00
IGL01339:Tmod4 APN 3 95128297 missense probably benign 0.23
IGL01785:Tmod4 APN 3 95125618 missense probably benign
IGL02160:Tmod4 APN 3 95129113 utr 3 prime probably benign
IGL02303:Tmod4 APN 3 95125642 missense probably benign 0.24
R0042:Tmod4 UTSW 3 95129788 unclassified possibly damaging 0.90
R1515:Tmod4 UTSW 3 95128679 missense possibly damaging 0.76
R4210:Tmod4 UTSW 3 95127829 missense probably benign 0.00
R4211:Tmod4 UTSW 3 95127829 missense probably benign 0.00
R6093:Tmod4 UTSW 3 95125618 missense probably benign
R6181:Tmod4 UTSW 3 95127807 missense probably damaging 1.00
R6294:Tmod4 UTSW 3 95128306 missense probably benign 0.05
R6351:Tmod4 UTSW 3 95127853 missense probably damaging 1.00
Nature of Mutation

DNA sequencing using the SOLiD technique identified a C to T transition at position 703 of the Scnm1 transcript.  Multiple transcripts of the Scnm1 gene are displayed on Ensembl. The mutated nucleotide causes a premature stop codon at amino acid 196 (normally an arginine), truncating 34 amino acids from the wild type isoform (Ensembl record ENSMUSP00000115570). This isoform is not present in C57BL/6J mice. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

 

Protein Function & Prediction
The Scnm1 gene encodes a 229 amino acid protein known as the sodium channel modifier 1 (SCNM1). SCNM1 may function as a RNA splicing factor. Three isoforms are described on Uniprot (Q8K136), the wild type protein and two isoforms found in C57BL/6J mice and related strains. Isoform 2 is prematurely truncated at residue 186 and isoform 3 lacks residues 132-196. The Scnm1 mutation described here does not further affect the protein.The Scnm1 locus influences the severity of mutations in the Scn8a gene (see the record for TremorD). Mice carrying the recessive susceptibility allele of the modifier, such as C57BL/6J mice, are paralyzed and do not survive beyond 1 month. Mice carrying the resistant wild type allele display progressive dystonia with ataxia and live more than 1.5 years. 
Posted OnMar 19, 2010