Incidental Mutation 'D3080:Smyd3'
ID112
Institutional Source Beutler Lab
Gene Symbol Smyd3
Ensembl Gene ENSMUSG00000055067
Gene NameSET and MYND domain containing 3
Synonyms2410008A19Rik, Zmynd1
Accession Numbers

Genbank: NM_027188; MGI: 1916976; Ensembl: ENSMUST00000128302, ENSMUST00000111134, ENSMUST00000111133

Is this an essential gene? Non essential (E-score: 0.000) question?
Stock #D3080 of strain grasshopper
Quality Score
Status Validated
Chromosome1
Chromosomal Location178951960-179518041 bp(-) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) A to G at 179086422 bp
ZygosityHeterozygous
Amino Acid Change Tyrosine to Histidine at position 239 (Y239H)
Ref Sequence ENSEMBL: ENSMUSP00000117410 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000128302]
Predicted Effect noncoding transcript
Transcript: ENSMUST00000068437
Predicted Effect probably damaging
Transcript: ENSMUST00000128302
AA Change: Y239H

PolyPhen 2 Score 0.999 (Sensitivity: 0.14; Specificity: 0.99)
SMART Domains Protein: ENSMUSP00000117410
Gene: ENSMUSG00000055067
AA Change: Y239H

DomainStartEndE-ValueType
SET 4 246 1.04e-11 SMART
low complexity region 410 420 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000131684
Meta Mutation Damage Score 0.8145 question?
Coding Region Coverage
  • 1x: 88.9%
  • 3x: 76.7%
Validation Efficiency 82% (141/173)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a histone methyltransferase which functions in RNA polymerase II complexes by an interaction with a specific RNA helicase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
PHENOTYPE: No abnormal phenotype was observed in a high-throughput screen, nor in a pathology assessment. [provided by MGI curators]
Allele List at MGI

All alleles(34) : Targeted, other(5) Gene trapped(29)

Other mutations in this stock
Total: 20 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
2310003L06Rik C A 5: 87,971,987 P201Q possibly damaging Het
Bdp1 A T 13: 100,023,621 S2417R probably benign Het
Dscaml1 A T 9: 45,684,325 H783L probably benign Het
Fbxl5 A T 5: 43,758,366 M568K probably benign Het
Gab1 T A 8: 80,766,378 D710V probably damaging Homo
Gabrr2 T C 4: 33,084,466 F128S probably damaging Het
Gm8251 C A 1: 44,067,335 Het
Hyou1 T A 9: 44,384,477 V343E probably damaging Het
Nlrp4a A G 7: 26,444,341 T44A probably benign Het
Nsd3 C A 8: 25,713,545 T1362N possibly damaging Homo
Olfr523 G A 7: 140,176,362 V81M possibly damaging Het
Pcm1 T A 8: 41,275,939 N649K probably damaging Homo
Pde4dip T C 3: 97,766,830 K257E probably damaging Het
Pfpl G A 19: 12,428,832 R149Q probably damaging Homo
Pou2f2 G T 7: 25,097,133 probably benign Het
Rptn A G 3: 93,395,828 D156G possibly damaging Het
Sec31a T C 5: 100,363,832 D1107G probably damaging Het
Stoml3 T C 3: 53,497,994 F32S probably benign Het
Tnnc1 C A 14: 31,210,190 D62E probably damaging Homo
Vsig10 C T 5: 117,343,819 A358V probably damaging Het
Other mutations in Smyd3
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL02044:Smyd3 APN 1 178972279 missense probably benign
IGL03088:Smyd3 APN 1 179094333 critical splice donor site probably null
R0165:Smyd3 UTSW 1 179043872 missense probably benign
R0230:Smyd3 UTSW 1 179423428 splice site probably benign
R0390:Smyd3 UTSW 1 178957573 splice site probably benign
R1651:Smyd3 UTSW 1 179043876 missense probably benign
R4651:Smyd3 UTSW 1 179043741 missense probably benign 0.08
R4771:Smyd3 UTSW 1 179094396 missense probably damaging 0.99
R5326:Smyd3 UTSW 1 179410459 missense probably benign
R5542:Smyd3 UTSW 1 179410459 missense probably benign
R5697:Smyd3 UTSW 1 179411682 missense probably damaging 1.00
R5850:Smyd3 UTSW 1 179043855 missense probably damaging 1.00
R6732:Smyd3 UTSW 1 179395830 missense probably benign 0.01
R7782:Smyd3 UTSW 1 178972294 missense possibly damaging 0.94
R8065:Smyd3 UTSW 1 179410463 missense possibly damaging 0.60
R8067:Smyd3 UTSW 1 179410463 missense possibly damaging 0.60
R8236:Smyd3 UTSW 1 179405640 splice site probably null
R8735:Smyd3 UTSW 1 179092917 missense probably benign 0.12
X0024:Smyd3 UTSW 1 179050289 critical splice donor site probably null
Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to C transition at position 767 of the Smyd3 transcript.  Multiple transcripts of the Smyd3 gene are displayed on Ensembl. The mutation causes a tyrosine to histidine change at amino acid 239 of the encoded protein using Ensembl record ENSMUSP00000117410. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction
The Smyd3  gene encodes a 428 amino acid histone methyltransferase that plays an important role in transcriptional activation. SMYD3 contains a MYND-type zinc finger at amino acids 49-87 and a SET domain at amino acids 126-246 (Uniprot Q9CWR2). 
 
The Y239H change is located in the SET domain in a conserved amino acid implicated in mediating methylation activity, and is predicted to be probably damaging by the PolyPhen program.
Posted On2010-03-11