Incidental Mutation 'R4454:Thrb'
| ID |
329102 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Thrb
|
| Ensembl Gene |
ENSMUSG00000021779 |
| Gene Name |
thyroid hormone receptor beta |
| Synonyms |
T3R[b], TR beta, c-erbAbeta, Nr1a2, Thrb1, Thrb2, T3Rbeta |
| MMRRC Submission |
041714-MU
|
| Accession Numbers |
|
| Essential gene? |
Possibly essential
(E-score: 0.623)
|
| Stock # |
R4454 (G1)
|
| Quality Score |
225 |
|
Status
|
Validated
|
| Chromosome |
14 |
| Chromosomal Location |
4431611-4809435 bp(-) (GRCm39) |
| Type of Mutation |
missense |
| DNA Base Change (assembly) |
T to A
at 18011187 bp (GRCm38)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Tryptophan to Arginine
at position 188
(W188R)
|
| Ref Sequence |
ENSEMBL: ENSMUSP00000153355
(fasta)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000022303]
[ENSMUST00000022304]
[ENSMUST00000091471]
[ENSMUST00000224934]
|
| AlphaFold |
P37242 |
| Predicted Effect |
probably benign
Transcript: ENSMUST00000022303
AA Change: W219R
PolyPhen 2
Score 0.162 (Sensitivity: 0.92; Specificity: 0.87)
|
| SMART Domains |
Protein: ENSMUSP00000022303
Gene: ENSMUSG00000021779
AA Change: W219R
| Domain | Start | End | E-Value | Type |
|---|
|
ZnF_C4
|
104 |
177 |
2.88e-36 |
SMART |
|
low complexity region
|
188 |
203 |
N/A |
INTRINSIC |
|
HOLI
|
274 |
432 |
9.29e-31 |
SMART |
|
| Predicted Effect |
possibly damaging
Transcript: ENSMUST00000022304
AA Change: W233R
PolyPhen 2
Score 0.882 (Sensitivity: 0.82; Specificity: 0.94)
|
| SMART Domains |
Protein: ENSMUSP00000022304
Gene: ENSMUSG00000021779
AA Change: W233R
| Domain | Start | End | E-Value | Type |
|---|
|
ZnF_C4
|
118 |
191 |
2.88e-36 |
SMART |
|
low complexity region
|
202 |
217 |
N/A |
INTRINSIC |
|
HOLI
|
288 |
446 |
9.29e-31 |
SMART |
|
| Predicted Effect |
probably benign
Transcript: ENSMUST00000091471
AA Change: W219R
PolyPhen 2
Score 0.162 (Sensitivity: 0.92; Specificity: 0.87)
|
| SMART Domains |
Protein: ENSMUSP00000089053
Gene: ENSMUSG00000021779
AA Change: W219R
| Domain | Start | End | E-Value | Type |
|---|
|
ZnF_C4
|
104 |
177 |
2.88e-36 |
SMART |
|
low complexity region
|
188 |
203 |
N/A |
INTRINSIC |
|
HOLI
|
274 |
432 |
9.29e-31 |
SMART |
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000224512
|
| Predicted Effect |
probably damaging
Transcript: ENSMUST00000224934
AA Change: W188R
PolyPhen 2
Score 0.971 (Sensitivity: 0.77; Specificity: 0.96)
|
| Predicted Effect |
noncoding transcript
Transcript: ENSMUST00000225876
|
| Meta Mutation Damage Score |
0.1099 |
| Coding Region Coverage |
- 1x: 99.2%
- 3x: 98.5%
- 10x: 96.9%
- 20x: 94.3%
|
| Validation Efficiency |
100% (51/51) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] The protein encoded by this gene is a nuclear hormone receptor for triiodothyronine. It is one of the several receptors for thyroid hormone, and has been shown to mediate the biological activities of thyroid hormone. Knockout studies in mice suggest that the different receptors, while having certain extent of redundancy, may mediate different functions of thyroid hormone. Mutations in this gene are known to be a cause of generalized thyroid hormone resistance (GTHR), a syndrome characterized by goiter and high levels of circulating thyroid hormone (T3-T4), with normal or slightly elevated thyroid stimulating hormone (TSH). Several alternatively spliced transcript variants encoding the same protein have been observed for this gene. [provided by RefSeq, Jul 2008]
PHENOTYPE: Mice homozygous for a knock-out allele exhibit elevated T3, T4, and TSH serum levels, abnormal ear morphology, deafness, and abnormal thyroid morphology. Mice homozygous for allele with point mutations exhibit disruption in thyroid hormone sensitivity. [provided by MGI curators]
|
| Allele List at MGI |
|
| Other mutations in this stock |
Total: 50 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| Ap4e1 |
T |
A |
2: 126,889,061 (GRCm39) |
F509I |
probably damaging |
Het |
| Asmt |
A |
T |
X: 169,106,456 (GRCm39) |
M19L |
probably benign |
Het |
| Atf6 |
C |
T |
1: 170,621,608 (GRCm39) |
R471Q |
probably damaging |
Het |
| Atp4a |
G |
A |
7: 30,419,650 (GRCm39) |
R671Q |
probably benign |
Het |
| Baiap3 |
T |
A |
17: 25,468,510 (GRCm39) |
D250V |
probably damaging |
Het |
| C2cd4d |
T |
A |
3: 94,271,054 (GRCm39) |
F107I |
probably damaging |
Het |
| Cdkn2d |
C |
G |
9: 21,202,185 (GRCm39) |
V21L |
probably benign |
Het |
| Cldn6 |
T |
C |
17: 23,900,060 (GRCm39) |
|
probably null |
Het |
| Cpa5 |
A |
G |
6: 30,626,323 (GRCm39) |
N228S |
possibly damaging |
Het |
| Cracdl |
T |
C |
1: 37,663,834 (GRCm39) |
E163G |
probably damaging |
Het |
| Crocc |
T |
C |
4: 140,747,716 (GRCm39) |
S1478G |
possibly damaging |
Het |
| Csmd1 |
A |
T |
8: 15,995,011 (GRCm39) |
C2675S |
probably damaging |
Het |
| Cthrc1 |
C |
A |
15: 38,940,408 (GRCm39) |
Q4K |
probably benign |
Het |
| Ddo |
A |
T |
10: 40,523,543 (GRCm39) |
I178F |
probably damaging |
Het |
| Dmxl1 |
A |
G |
18: 50,026,399 (GRCm39) |
T1836A |
probably benign |
Het |
| Dnah9 |
T |
G |
11: 66,038,215 (GRCm39) |
Q107P |
probably damaging |
Het |
| Dusp26 |
A |
G |
8: 31,584,172 (GRCm39) |
N93S |
probably damaging |
Het |
| Egr2 |
GAA |
GA |
10: 67,375,733 (GRCm39) |
|
probably null |
Het |
| Epha5 |
T |
C |
5: 84,304,303 (GRCm39) |
I501V |
probably damaging |
Het |
| Eya1 |
C |
T |
1: 14,253,420 (GRCm39) |
V519M |
probably damaging |
Het |
| Fam227b |
T |
A |
2: 125,988,188 (GRCm39) |
|
probably benign |
Het |
| Fgd5 |
C |
T |
6: 91,966,167 (GRCm39) |
S642F |
probably damaging |
Het |
| Fsip2 |
G |
T |
2: 82,821,120 (GRCm39) |
A5618S |
possibly damaging |
Het |
| Gm12034 |
T |
A |
11: 20,396,476 (GRCm39) |
|
noncoding transcript |
Het |
| Liph |
T |
C |
16: 21,803,018 (GRCm39) |
D17G |
probably benign |
Het |
| Mbd3 |
A |
T |
10: 80,229,817 (GRCm39) |
L164H |
probably damaging |
Het |
| Med4 |
A |
G |
14: 73,755,502 (GRCm39) |
|
probably benign |
Het |
| Mslnl |
G |
A |
17: 25,961,908 (GRCm39) |
V128M |
probably damaging |
Het |
| Nav2 |
A |
T |
7: 49,198,292 (GRCm39) |
|
probably null |
Het |
| Or4k1 |
T |
C |
14: 50,377,953 (GRCm39) |
I48V |
probably benign |
Het |
| Or8b1b |
C |
A |
9: 38,375,938 (GRCm39) |
F200L |
probably benign |
Het |
| Pcdha11 |
G |
A |
18: 37,140,426 (GRCm39) |
G685D |
probably benign |
Het |
| Pgc |
A |
G |
17: 48,043,335 (GRCm39) |
I228V |
probably benign |
Het |
| Pramel25 |
A |
G |
4: 143,519,394 (GRCm39) |
S52G |
probably benign |
Het |
| Rad51 |
C |
T |
2: 118,962,049 (GRCm39) |
H199Y |
probably damaging |
Het |
| Robo2 |
A |
T |
16: 74,149,407 (GRCm39) |
|
probably benign |
Het |
| Sap130 |
C |
T |
18: 31,844,413 (GRCm39) |
T861I |
probably damaging |
Het |
| Sh3tc2 |
A |
T |
18: 62,140,844 (GRCm39) |
D1061V |
probably damaging |
Het |
| Shoc1 |
T |
C |
4: 59,092,383 (GRCm39) |
D266G |
possibly damaging |
Het |
| Snapc3 |
A |
G |
4: 83,336,996 (GRCm39) |
E119G |
probably damaging |
Het |
| Sspo |
G |
A |
6: 48,464,159 (GRCm39) |
G3862D |
probably benign |
Het |
| Tbc1d16 |
G |
A |
11: 119,048,699 (GRCm39) |
T318M |
possibly damaging |
Het |
| Thsd1 |
T |
C |
8: 22,733,594 (GRCm39) |
Y214H |
probably damaging |
Het |
| Tnfrsf13b |
T |
C |
11: 61,032,264 (GRCm39) |
V98A |
probably benign |
Het |
| Topbp1 |
T |
C |
9: 103,222,070 (GRCm39) |
Y1314H |
probably damaging |
Het |
| Ttn |
C |
A |
2: 76,616,150 (GRCm39) |
V8271L |
possibly damaging |
Het |
| Ttn |
T |
C |
2: 76,777,257 (GRCm39) |
M1382V |
probably benign |
Het |
| Utrn |
G |
T |
10: 12,603,584 (GRCm39) |
Q599K |
possibly damaging |
Het |
| Zfp995 |
G |
A |
17: 22,098,932 (GRCm39) |
T434I |
probably benign |
Het |
| Zfy1 |
G |
T |
Y: 725,518 (GRCm39) |
T749K |
possibly damaging |
Het |
|
| Other mutations in Thrb |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL01302:Thrb
|
APN |
14 |
18,011,056 (GRCm38) |
splice site |
probably benign |
|
|
IGL02488:Thrb
|
APN |
14 |
18,033,455 (GRCm38) |
missense |
probably damaging |
0.98 |
|
IGL02598:Thrb
|
APN |
14 |
18,008,606 (GRCm38) |
missense |
possibly damaging |
0.95 |
|
IGL02707:Thrb
|
APN |
14 |
18,026,721 (GRCm38) |
missense |
probably benign |
0.42 |
|
harry
|
UTSW |
14 |
18,011,145 (GRCm38) |
nonsense |
probably null |
|
|
R0479:Thrb
|
UTSW |
14 |
18,033,643 (GRCm38) |
missense |
probably damaging |
0.99 |
|
R0988:Thrb
|
UTSW |
14 |
17,981,837 (GRCm38) |
intron |
probably benign |
|
|
R1257:Thrb
|
UTSW |
14 |
18,008,642 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R1522:Thrb
|
UTSW |
14 |
18,002,597 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R1927:Thrb
|
UTSW |
14 |
18,008,674 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R2100:Thrb
|
UTSW |
14 |
18,030,393 (GRCm38) |
missense |
possibly damaging |
0.73 |
|
R2134:Thrb
|
UTSW |
14 |
18,033,487 (GRCm38) |
missense |
probably benign |
0.22 |
|
R3551:Thrb
|
UTSW |
14 |
17,963,214 (GRCm38) |
missense |
probably damaging |
0.99 |
|
R3888:Thrb
|
UTSW |
14 |
18,033,551 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R3975:Thrb
|
UTSW |
14 |
18,033,456 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R4294:Thrb
|
UTSW |
14 |
18,011,145 (GRCm38) |
nonsense |
probably null |
|
|
R4371:Thrb
|
UTSW |
14 |
18,030,275 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R4457:Thrb
|
UTSW |
14 |
18,011,187 (GRCm38) |
missense |
probably damaging |
0.97 |
|
R4486:Thrb
|
UTSW |
14 |
17,925,640 (GRCm38) |
start codon destroyed |
probably null |
0.72 |
|
R4961:Thrb
|
UTSW |
14 |
18,011,076 (GRCm38) |
missense |
probably benign |
0.39 |
|
R5184:Thrb
|
UTSW |
14 |
18,011,181 (GRCm38) |
nonsense |
probably null |
|
|
R5609:Thrb
|
UTSW |
14 |
18,033,526 (GRCm38) |
missense |
probably benign |
0.22 |
|
R6023:Thrb
|
UTSW |
14 |
18,011,209 (GRCm38) |
missense |
probably damaging |
0.98 |
|
R6891:Thrb
|
UTSW |
14 |
17,981,899 (GRCm38) |
missense |
probably benign |
|
|
R7288:Thrb
|
UTSW |
14 |
18,030,186 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R7294:Thrb
|
UTSW |
14 |
17,826,963 (GRCm38) |
start gained |
probably benign |
|
|
R7780:Thrb
|
UTSW |
14 |
18,008,608 (GRCm38) |
missense |
possibly damaging |
0.73 |
|
R8098:Thrb
|
UTSW |
14 |
18,008,645 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R8739:Thrb
|
UTSW |
14 |
17,963,082 (GRCm38) |
missense |
probably benign |
0.04 |
|
R8788:Thrb
|
UTSW |
14 |
18,002,558 (GRCm38) |
missense |
probably damaging |
1.00 |
|
R8978:Thrb
|
UTSW |
14 |
17,981,886 (GRCm38) |
missense |
possibly damaging |
0.84 |
|
R9314:Thrb
|
UTSW |
14 |
17,963,208 (GRCm38) |
missense |
probably benign |
|
|
Z1177:Thrb
|
UTSW |
14 |
18,033,433 (GRCm38) |
missense |
probably damaging |
1.00 |
|
| Predicted Primers |
PCR Primer
(F):5'- AGCTCTGGATTAGCAATGGG -3'
(R):5'- AGCCTCTGTAACCTCATTGGC -3'
Sequencing Primer
(F):5'- GGATTAGCAATGGGTCCTCTCAC -3'
(R):5'- TGAGCTGCAACTGCCCATC -3'
|
| Posted On |
2015-07-21 |
Incidental Mutation