Incidental Mutation '2107:Tmod4'
ID 145
Institutional Source Beutler Lab
Gene Symbol Tmod4
Ensembl Gene ENSMUSG00000005628
Gene Name tropomodulin 4
Synonyms skeletal tropomodulin, MTMOD, Sk-Tmod
Accession Numbers
Essential gene? Probably non essential (E-score: 0.155) question?
Stock # 2107 of strain triaka
Quality Score
Status Validated
Chromosome 3
Chromosomal Location 95031787-95036520 bp(+) (GRCm39)
Type of Mutation splice site
DNA Base Change (assembly) G to A at 95037479 bp (GRCm39)
Zygosity Homozygous
Amino Acid Change
Ref Sequence ENSEMBL: ENSMUSP00000067811 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000005769] [ENSMUST00000066386] [ENSMUST00000107227] [ENSMUST00000131597] [ENSMUST00000172572] [ENSMUST00000173462]
AlphaFold Q9JLH8
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: ENSMUST00000174508
Predicted Effect noncoding transcript
Transcript: ENSMUST00000174835
Predicted Effect noncoding transcript
Transcript: ENSMUST00000199730
Predicted Effect noncoding transcript
Transcript: ENSMUST00000149898
Predicted Effect noncoding transcript
Transcript: ENSMUST00000196728
Predicted Effect noncoding transcript
Transcript: ENSMUST00000173527
Predicted Effect noncoding transcript
Transcript: ENSMUST00000174859
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
Meta Mutation Damage Score 0.9755 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: 117,726,387 (GRCm39) N198K probably damaging Homo
Fam184a T C 10: 53,517,153 (GRCm39) E374G probably damaging Homo
Mypn C T 10: 63,039,530 (GRCm39) probably benign Homo
Nme7 T A 1: 164,172,922 (GRCm39) I211N possibly damaging Het
Wfs1 C T 5: 37,124,617 (GRCm39) R758H probably damaging Het
Zfp112 T C 7: 23,826,266 (GRCm39) C745R probably damaging Het
Other mutations in Tmod4
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00851:Tmod4 APN 3 95,032,891 (GRCm39) missense probably damaging 1.00
IGL01339:Tmod4 APN 3 95,035,608 (GRCm39) missense probably benign 0.23
IGL01785:Tmod4 APN 3 95,032,929 (GRCm39) missense probably benign
IGL02160:Tmod4 APN 3 95,036,424 (GRCm39) unclassified probably benign
IGL02303:Tmod4 APN 3 95,032,953 (GRCm39) missense probably benign 0.24
R0042:Tmod4 UTSW 3 95,037,099 (GRCm39) missense possibly damaging 0.90
R1515:Tmod4 UTSW 3 95,035,990 (GRCm39) missense possibly damaging 0.76
R4210:Tmod4 UTSW 3 95,035,140 (GRCm39) missense probably benign 0.00
R4211:Tmod4 UTSW 3 95,035,140 (GRCm39) missense probably benign 0.00
R6093:Tmod4 UTSW 3 95,032,929 (GRCm39) missense probably benign
R6181:Tmod4 UTSW 3 95,035,118 (GRCm39) missense probably damaging 1.00
R6294:Tmod4 UTSW 3 95,035,617 (GRCm39) missense probably benign 0.05
R6351:Tmod4 UTSW 3 95,035,164 (GRCm39) missense probably damaging 1.00
R7417:Tmod4 UTSW 3 95,033,174 (GRCm39) missense possibly damaging 0.87
R7806:Tmod4 UTSW 3 95,034,915 (GRCm39) missense probably benign 0.00
R8272:Tmod4 UTSW 3 95,033,171 (GRCm39) missense probably damaging 0.99
R8921:Tmod4 UTSW 3 95,033,289 (GRCm39) critical splice donor site probably null
R9508:Tmod4 UTSW 3 95,034,713 (GRCm39) missense probably benign 0.00
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 and 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 On 2010-03-19