Incidental Mutation 'G5030:Trim37'
| ID |
489 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Trim37
|
| Ensembl Gene |
ENSMUSG00000018548 |
| Gene Name |
tripartite motif-containing 37 |
| Synonyms |
MUL, TEF3, 1110032A10Rik, 2810004E07Rik |
| Accession Numbers |
|
| Essential gene? |
Non essential
(E-score: 0.000)
|
| Stock # |
G5030 (G3)
of strain
560
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
11 |
| Chromosomal Location |
87017903-87111509 bp(+) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
A to T
at 87033967 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Histidine to Leucine
at position 99
(H99L)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000049057
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000041282]
[ENSMUST00000139532]
|
| AlphaFold |
Q6PCX9 |
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000041282
AA Change: H99L
PolyPhen 2
Score 0.963 (Sensitivity: 0.78; Specificity: 0.95)
|
| SMART Domains |
Protein: ENSMUSP00000049057
Gene: ENSMUSG00000018548
AA Change: H99L
| Domain | Start | End | E-Value | Type |
|---|
|
RING
|
15 |
54 |
1.71e-1 |
SMART |
|
BBOX
|
90 |
132 |
7.32e-12 |
SMART |
|
BBC
|
132 |
254 |
3.05e-31 |
SMART |
|
MATH
|
281 |
384 |
1.51e-13 |
SMART |
|
low complexity region
|
494 |
504 |
N/A |
INTRINSIC |
|
low complexity region
|
516 |
529 |
N/A |
INTRINSIC |
|
low complexity region
|
535 |
545 |
N/A |
INTRINSIC |
|
low complexity region
|
579 |
588 |
N/A |
INTRINSIC |
|
low complexity region
|
612 |
626 |
N/A |
INTRINSIC |
|
low complexity region
|
795 |
808 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000139532
AA Change: H84L
PolyPhen 2
Score 0.251 (Sensitivity: 0.91; Specificity: 0.88)
|
| SMART Domains |
Protein: ENSMUSP00000119269
Gene: ENSMUSG00000018548
AA Change: H84L
| Domain | Start | End | E-Value | Type |
|---|
|
BBOX
|
75 |
117 |
7.32e-12 |
SMART |
|
| Meta Mutation Damage Score |
0.1920 |
| Coding Region Coverage |
|
| Het Detection Efficiency |
35.6% |
| Validation Efficiency |
87% (206/237) |
| MGI Phenotype |
FUNCTION: The protein encoded by this gene is part of the tripartite-motif containing family (TRIM), which is typified by the RING, B-box type 1, B-box type 2, and coiled-coil region domains. In mouse this protein is proposed to oligomerize through its coiled coil domain and has been reported to be expressed in neural crest-derived tissues as well as in tissues whose development is regulated by mesenchymal-epithelial interactions. In humans, mutations in this gene are associated with mulibrey (muscle-liver-brain-eye) nanism, an autosomal recessive disorder characterized by prenatal onset growth failure, cardiomyopathy and dysmorphic features. [provided by RefSeq, Jan 2013]
PHENOTYPE: Mice homozygous for a knock-out allele are infertile due to gonadal degeneration and exhibit late-onset weight loss, smaller skull size, non-compaction cardiomyopathy, hepatomegaly, fatty liver, altered glucose metabolism, splenomegaly, and increased tumor incidence. [provided by MGI curators]
|
| Allele List at MGI |
All alleles(7) : Gene trapped(7) |
| Other mutations in this stock |
Total: 30 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Abca8a |
T |
A |
11: 109,961,165 (GRCm39) |
I585F |
probably damaging |
Het |
| Adam18 |
C |
G |
8: 25,141,872 (GRCm39) |
L232F |
probably benign |
Homo |
| Atp13a4 |
A |
G |
16: 29,274,306 (GRCm39) |
I385T |
probably damaging |
Homo |
| Ccdc17 |
T |
A |
4: 116,455,699 (GRCm39) |
S277T |
probably benign |
Het |
| Ccng1 |
A |
G |
11: 40,644,629 (GRCm39) |
|
probably benign |
Het |
| Ces1f |
T |
C |
8: 94,000,847 (GRCm39) |
D99G |
probably benign |
Het |
| Clec16a |
G |
A |
16: 10,389,425 (GRCm39) |
R187Q |
probably damaging |
Homo |
| Cryl1 |
C |
T |
14: 57,579,595 (GRCm39) |
|
probably benign |
Het |
| Cryzl2 |
C |
T |
1: 157,292,580 (GRCm39) |
Q48* |
probably null |
Het |
| Dtx4 |
A |
G |
19: 12,446,943 (GRCm39) |
L583P |
probably benign |
Het |
| Ephx4 |
A |
T |
5: 107,577,693 (GRCm39) |
D339V |
probably damaging |
Het |
| Eri2 |
A |
T |
7: 119,385,601 (GRCm39) |
V300E |
possibly damaging |
Het |
| F3 |
T |
A |
3: 121,518,648 (GRCm39) |
N37K |
probably damaging |
Homo |
| Fpr1 |
A |
T |
17: 18,097,068 (GRCm39) |
L307H |
probably damaging |
Het |
| Fv1 |
T |
A |
4: 147,953,618 (GRCm39) |
N61K |
possibly damaging |
Het |
| Gm5548 |
T |
C |
3: 112,961,512 (GRCm39) |
|
noncoding transcript |
Homo |
| Il1r1 |
A |
G |
1: 40,352,323 (GRCm39) |
K498E |
possibly damaging |
Homo |
| Myh11 |
T |
C |
16: 14,068,443 (GRCm39) |
I192M |
probably damaging |
Homo |
| Nckap5 |
T |
C |
1: 125,953,591 (GRCm39) |
K923R |
probably damaging |
Het |
| Nmbr |
A |
T |
10: 14,642,747 (GRCm39) |
Y102F |
possibly damaging |
Het |
| Or6c75 |
A |
G |
10: 129,337,406 (GRCm39) |
T218A |
probably benign |
Homo |
| Pde1a |
C |
T |
2: 79,718,180 (GRCm39) |
|
probably benign |
Het |
| Pex6 |
T |
C |
17: 47,026,382 (GRCm39) |
|
probably benign |
Het |
| Rtn2 |
T |
C |
7: 19,027,099 (GRCm39) |
S305P |
probably damaging |
Homo |
| Saal1 |
G |
A |
7: 46,342,207 (GRCm39) |
T412I |
probably damaging |
Homo |
| Slc46a2 |
A |
T |
4: 59,913,867 (GRCm39) |
I352N |
probably damaging |
Het |
| Tubgcp4 |
C |
T |
2: 121,014,815 (GRCm39) |
R242C |
probably damaging |
Het |
| Twf2 |
C |
A |
9: 106,084,141 (GRCm39) |
L27I |
possibly damaging |
Het |
| Usp40 |
A |
T |
1: 87,921,941 (GRCm39) |
H307Q |
probably damaging |
Het |
| Zfhx3 |
T |
G |
8: 109,678,091 (GRCm39) |
V3047G |
possibly damaging |
Het |
|
| Other mutations in Trim37 |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00708:Trim37
|
APN |
11 |
87,077,219 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01372:Trim37
|
APN |
11 |
87,075,772 (GRCm39) |
missense |
probably benign |
0.00 |
|
IGL01510:Trim37
|
APN |
11 |
87,068,686 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02055:Trim37
|
APN |
11 |
87,057,475 (GRCm39) |
missense |
probably benign |
0.44 |
|
IGL02106:Trim37
|
APN |
11 |
87,092,230 (GRCm39) |
nonsense |
probably null |
|
|
IGL02251:Trim37
|
APN |
11 |
87,058,256 (GRCm39) |
splice site |
probably benign |
|
|
IGL02498:Trim37
|
APN |
11 |
87,075,876 (GRCm39) |
missense |
probably benign |
|
|
IGL02836:Trim37
|
APN |
11 |
87,087,785 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL03089:Trim37
|
APN |
11 |
87,080,963 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL03302:Trim37
|
APN |
11 |
87,037,827 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
IGL03347:Trim37
|
APN |
11 |
87,092,447 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R0396:Trim37
|
UTSW |
11 |
87,037,794 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R0544:Trim37
|
UTSW |
11 |
87,036,328 (GRCm39) |
nonsense |
probably null |
|
|
R0946:Trim37
|
UTSW |
11 |
87,037,781 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R1481:Trim37
|
UTSW |
11 |
87,020,585 (GRCm39) |
nonsense |
probably null |
|
|
R1799:Trim37
|
UTSW |
11 |
87,068,845 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R1851:Trim37
|
UTSW |
11 |
87,109,132 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2107:Trim37
|
UTSW |
11 |
87,050,651 (GRCm39) |
missense |
probably benign |
0.04 |
|
R3878:Trim37
|
UTSW |
11 |
87,096,828 (GRCm39) |
missense |
probably benign |
0.10 |
|
R4049:Trim37
|
UTSW |
11 |
87,031,429 (GRCm39) |
critical splice donor site |
probably null |
|
|
R4224:Trim37
|
UTSW |
11 |
87,107,289 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4486:Trim37
|
UTSW |
11 |
87,087,651 (GRCm39) |
missense |
probably benign |
0.31 |
|
R5244:Trim37
|
UTSW |
11 |
87,109,083 (GRCm39) |
missense |
probably benign |
0.10 |
|
R5343:Trim37
|
UTSW |
11 |
87,028,429 (GRCm39) |
missense |
probably damaging |
0.98 |
|
R5417:Trim37
|
UTSW |
11 |
87,057,505 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R5894:Trim37
|
UTSW |
11 |
87,092,266 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R5911:Trim37
|
UTSW |
11 |
87,087,663 (GRCm39) |
nonsense |
probably null |
|
|
R5957:Trim37
|
UTSW |
11 |
87,036,377 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R6159:Trim37
|
UTSW |
11 |
87,107,374 (GRCm39) |
critical splice donor site |
probably null |
|
|
R6479:Trim37
|
UTSW |
11 |
87,107,313 (GRCm39) |
nonsense |
probably null |
|
|
R6527:Trim37
|
UTSW |
11 |
87,080,910 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7021:Trim37
|
UTSW |
11 |
87,058,335 (GRCm39) |
missense |
probably benign |
0.01 |
|
R7734:Trim37
|
UTSW |
11 |
87,068,821 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R7849:Trim37
|
UTSW |
11 |
87,092,270 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
R7938:Trim37
|
UTSW |
11 |
87,037,863 (GRCm39) |
missense |
probably benign |
0.05 |
|
R7968:Trim37
|
UTSW |
11 |
87,040,179 (GRCm39) |
missense |
possibly damaging |
0.47 |
|
R8046:Trim37
|
UTSW |
11 |
87,037,794 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R8112:Trim37
|
UTSW |
11 |
87,109,093 (GRCm39) |
missense |
possibly damaging |
0.80 |
|
R8735:Trim37
|
UTSW |
11 |
87,037,885 (GRCm39) |
critical splice donor site |
probably null |
|
|
R8770:Trim37
|
UTSW |
11 |
87,050,675 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R8911:Trim37
|
UTSW |
11 |
87,097,629 (GRCm39) |
missense |
possibly damaging |
0.89 |
|
R9234:Trim37
|
UTSW |
11 |
87,036,393 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R9332:Trim37
|
UTSW |
11 |
87,058,328 (GRCm39) |
missense |
possibly damaging |
0.94 |
|
R9346:Trim37
|
UTSW |
11 |
87,057,426 (GRCm39) |
critical splice acceptor site |
probably null |
|
|
R9431:Trim37
|
UTSW |
11 |
87,077,257 (GRCm39) |
missense |
probably benign |
0.34 |
|
Z1177:Trim37
|
UTSW |
11 |
87,075,869 (GRCm39) |
missense |
probably benign |
|
|
| Nature of Mutation |
 DNA sequencing using the SOLiD technique identified an A to T transversion at position 693 of the Trim37 transcript in exon 5 of 24 total exons. Multiple transcripts of the Trim37 gene are displayed on Ensembl and Vega. The mutated nucleotide causes a histidine to leucine substitution at amino acid 99 of the encoded protein. The mutation has been confirmed by DNA sequencing using the Sanger method (Figure 1).
|
| Protein Function and Prediction |
The Trim37 gene encodes a 961 amino acid E3 ubiquitin-protein ligase, a member of the RING B-box coiled-coil (RBCC) family of zinc finger proteins. The protein is found in peroxisomal vesicles and in a perinuclear region known as the aggresome where misfolded or aggregated proteins are sequestered for proteosomal degradation. TRIM37 contains a RING-type zinc finger at residues 15-55, a B box-type zinc finger at residues 90-132, two coiled coil domains at residues 132-234 and 419-450, and a meprin and TRAF homology (MATH) domain at residues 276-403 (Uniprot Q6PCX9). Mutations in this gene in humans causes mulibrey nanism (OMIM 253250), a disorder characterized by progressive growth failure.
The H99L change occurs in the B box-type zinc finger, and is predicted to be probably damaging by the PolyPhen program (see report).
|
| Posted On |
2010-10-26 |
Incidental Mutation