Incidental Mutation 'A5278:Tdrd7'
ID 62
Institutional Source Beutler Lab
Gene Symbol Tdrd7
Ensembl Gene ENSMUSG00000035517
Gene Name tudor domain containing 7
Synonyms 5730495N10Rik
Accession Numbers
Essential gene? Possibly essential (E-score: 0.540) question?
Stock # A5278 of strain 453
Quality Score
Status Validated
Chromosome 4
Chromosomal Location 45965334-46034761 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) C to T at 46007622 bp (GRCm39)
Zygosity Homozygous
Amino Acid Change Threonine to Methionine at position 558 (T558M)
Ref Sequence ENSEMBL: ENSMUSP00000103406 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000102929] [ENSMUST00000107777]
AlphaFold Q8K1H1
Predicted Effect probably benign
Transcript: ENSMUST00000102929
AA Change: T525M

PolyPhen 2 Score 0.004 (Sensitivity: 0.98; Specificity: 0.59)
SMART Domains Protein: ENSMUSP00000099993
Gene: ENSMUSG00000035517
AA Change: T525M

DomainStartEndE-ValueType
Pfam:OST-HTH 3 73 2.6e-10 PFAM
internal_repeat_1 223 300 2.94e-9 PROSPERO
low complexity region 302 318 N/A INTRINSIC
internal_repeat_1 326 400 2.94e-9 PROSPERO
TUDOR 500 556 2.08e-5 SMART
TUDOR 690 746 1.66e-4 SMART
TUDOR 945 1001 4.03e0 SMART
Predicted Effect probably benign
Transcript: ENSMUST00000107777
AA Change: T558M

PolyPhen 2 Score 0.007 (Sensitivity: 0.96; Specificity: 0.75)
SMART Domains Protein: ENSMUSP00000103406
Gene: ENSMUSG00000035517
AA Change: T558M

DomainStartEndE-ValueType
Pfam:OST-HTH 36 106 5.7e-11 PFAM
internal_repeat_1 256 333 3.1e-9 PROSPERO
low complexity region 335 351 N/A INTRINSIC
internal_repeat_1 359 433 3.1e-9 PROSPERO
TUDOR 533 589 2.08e-5 SMART
TUDOR 723 779 1.66e-4 SMART
TUDOR 978 1034 4.03e0 SMART
Predicted Effect noncoding transcript
Transcript: ENSMUST00000140270
Meta Mutation Damage Score 0.0898 question?
Coding Region Coverage
  • 1x: 88.2%
  • 3x: 73.8%
Validation Efficiency 87% (116/134)
MGI Phenotype FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene belongs to the Tudor family of proteins. This protein contains conserved Tudor domains and LOTUS domains. It is a component of RNA granules, which function in RNA processing. Mutations in this gene have been associated with cataract formation in mouse and human. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]
PHENOTYPE: Homozygous inactivation of this gene causes arrest of spermatogenesis, male sterility, glaucoma, and cataracts. Aging mice homozygous for an ENU-induced (null) allele show additional ocular phenotypes including an enlarged anterior chamber, lens extrusion, a flat iris, uveitis, and optic neuropathy. [provided by MGI curators]
Allele List at MGI

All alleles(1) : Gene trapped(1)

Other mutations in this stock
Total: 7 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Kat14 C A 2: 144,235,227 (GRCm39) S18* probably null Het
Kif17 T C 4: 138,015,261 (GRCm39) V278A probably benign Homo
Myo3a A G 2: 22,328,464 (GRCm39) T353A probably benign Het
Pbk T A 14: 66,051,388 (GRCm39) I142N probably damaging Het
Rab32 A G 10: 10,433,717 (GRCm39) I39T possibly damaging Het
Rhou G T 8: 124,387,730 (GRCm39) C154F probably damaging Het
Slc4a1 A G 11: 102,244,641 (GRCm39) probably benign Het
Other mutations in Tdrd7
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00491:Tdrd7 APN 4 46,010,889 (GRCm39) missense probably damaging 1.00
IGL01541:Tdrd7 APN 4 46,018,551 (GRCm39) missense possibly damaging 0.90
IGL01901:Tdrd7 APN 4 45,989,225 (GRCm39) splice site probably benign
IGL02812:Tdrd7 APN 4 45,994,406 (GRCm39) missense probably benign 0.08
R0049:Tdrd7 UTSW 4 45,987,582 (GRCm39) missense probably damaging 1.00
R0049:Tdrd7 UTSW 4 45,987,582 (GRCm39) missense probably damaging 1.00
R0389:Tdrd7 UTSW 4 46,016,987 (GRCm39) missense probably benign 0.01
R0452:Tdrd7 UTSW 4 45,965,488 (GRCm39) splice site probably benign
R0639:Tdrd7 UTSW 4 45,989,102 (GRCm39) missense probably benign 0.00
R0681:Tdrd7 UTSW 4 46,016,879 (GRCm39) missense probably benign 0.45
R0925:Tdrd7 UTSW 4 46,025,758 (GRCm39) missense probably damaging 1.00
R0944:Tdrd7 UTSW 4 46,029,762 (GRCm39) missense probably benign 0.01
R1586:Tdrd7 UTSW 4 45,994,445 (GRCm39) missense probably benign 0.39
R1770:Tdrd7 UTSW 4 45,987,681 (GRCm39) splice site probably benign
R1945:Tdrd7 UTSW 4 45,965,474 (GRCm39) missense probably benign 0.00
R4400:Tdrd7 UTSW 4 46,005,540 (GRCm39) missense possibly damaging 0.87
R4457:Tdrd7 UTSW 4 46,007,526 (GRCm39) missense probably benign 0.04
R4898:Tdrd7 UTSW 4 46,005,616 (GRCm39) missense possibly damaging 0.94
R5152:Tdrd7 UTSW 4 46,013,191 (GRCm39) missense probably damaging 1.00
R5197:Tdrd7 UTSW 4 46,034,350 (GRCm39) missense probably damaging 1.00
R5326:Tdrd7 UTSW 4 46,029,757 (GRCm39) missense probably benign 0.01
R5473:Tdrd7 UTSW 4 46,020,877 (GRCm39) missense possibly damaging 0.95
R5524:Tdrd7 UTSW 4 46,034,301 (GRCm39) missense probably benign 0.31
R5542:Tdrd7 UTSW 4 46,029,757 (GRCm39) missense probably benign 0.01
R5554:Tdrd7 UTSW 4 46,005,358 (GRCm39) missense possibly damaging 0.92
R5588:Tdrd7 UTSW 4 45,992,225 (GRCm39) missense probably benign 0.18
R5776:Tdrd7 UTSW 4 46,005,689 (GRCm39) missense probably benign 0.00
R5786:Tdrd7 UTSW 4 45,989,082 (GRCm39) missense probably benign 0.09
R6063:Tdrd7 UTSW 4 46,005,486 (GRCm39) missense probably benign 0.00
R6340:Tdrd7 UTSW 4 45,994,517 (GRCm39) missense probably damaging 0.99
R7130:Tdrd7 UTSW 4 46,029,693 (GRCm39) missense probably damaging 1.00
R7369:Tdrd7 UTSW 4 46,013,239 (GRCm39) missense possibly damaging 0.79
R7470:Tdrd7 UTSW 4 45,990,144 (GRCm39) missense probably benign 0.32
R7876:Tdrd7 UTSW 4 46,025,684 (GRCm39) missense probably benign
R7999:Tdrd7 UTSW 4 46,010,902 (GRCm39) critical splice donor site probably null
R8042:Tdrd7 UTSW 4 45,987,516 (GRCm39) missense possibly damaging 0.71
R8058:Tdrd7 UTSW 4 46,034,309 (GRCm39) missense probably benign 0.34
R8532:Tdrd7 UTSW 4 46,016,920 (GRCm39) missense probably damaging 0.98
R8771:Tdrd7 UTSW 4 46,010,800 (GRCm39) missense probably damaging 1.00
R8836:Tdrd7 UTSW 4 45,987,570 (GRCm39) missense probably damaging 1.00
R9033:Tdrd7 UTSW 4 46,007,468 (GRCm39) missense probably damaging 1.00
R9313:Tdrd7 UTSW 4 46,005,319 (GRCm39) missense probably benign 0.00
R9390:Tdrd7 UTSW 4 46,005,416 (GRCm39) missense probably damaging 1.00
R9683:Tdrd7 UTSW 4 46,025,946 (GRCm39) missense probably damaging 0.99
R9696:Tdrd7 UTSW 4 46,016,888 (GRCm39) missense possibly damaging 0.60
R9745:Tdrd7 UTSW 4 45,994,310 (GRCm39) missense possibly damaging 0.93
X0063:Tdrd7 UTSW 4 45,992,268 (GRCm39) missense probably benign 0.00
Nature of Mutation

DNA sequencing using the SOLiD technique identified a T to A transversion at position 1594 of the Tdrd7 transcript in exon 8 of 17 total exons.  Multiple transcripts of Tdrd7 gene are displayed on Ensembl. The mutated nucleotide causes a threonine to methionine substitution at amino acid 525 in the standard isoform of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).

Protein Function and Prediction
The Tdrd7 gene encodes a 1086 amino acid protein known as Trap that is found in a couple of messenger ribonucleoprotein (mRNP) complexes and interacts with a number of other proteins found in these complexes.  Trap is present in the chromatoid body (CB) of spermatids and spermatocytes spermatocytes.  Trap contains two Tudor domains (residues 501-558 and 691-748), which are found in many proteins that colocalise with ribonucleoprotein or single-strand DNA-associated complexes in the nucleus, in the mitochondrial membrane, or at kinetochores (Uniprot Q8K1H1).
 
The T525M change occurs in the first Tudor domain of the protein, and is predicted to be benign by the PolyPhen program.
Posted On 2009-12-03