Incidental Mutation 'R0066:Tbcd'
| ID |
16475 |
| Institutional Source |
Beutler Lab
|
| Gene Symbol |
Tbcd
|
| Ensembl Gene |
ENSMUSG00000039230 |
| Gene Name |
tubulin-specific chaperone d |
| Synonyms |
2310057L06Rik, A030005L14Rik |
| MMRRC Submission |
038357-MU
|
| Accession Numbers |
|
| Essential gene? |
Probably essential
(E-score: 0.957)
|
| Stock # |
R0066 (G1)
|
| Quality Score |
|
|
Status
|
Validated
|
| Chromosome |
11 |
| Chromosomal Location |
121342817-121507996 bp(+) (GRCm39) |
| Type of Mutation |
nonsense |
| DNA Base Change (assembly) |
T to A
at 121394590 bp (GRCm39)
|
| Zygosity |
Heterozygous |
| Amino Acid Change |
Leucine to Stop codon
at position 49
(L49*)
|
| Gene Model |
predicted gene model for transcript(s):
[ENSMUST00000103013]
|
| AlphaFold |
Q8BYA0 |
| Predicted Effect |
probably null
Transcript: ENSMUST00000103013
AA Change: L434*
|
| SMART Domains |
Protein: ENSMUSP00000099302
Gene: ENSMUSG00000039230
AA Change: L434*
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
6 |
20 |
N/A |
INTRINSIC |
|
low complexity region
|
45 |
62 |
N/A |
INTRINSIC |
|
SCOP:d1b3ua_
|
357 |
742 |
4e-20 |
SMART |
|
Pfam:TFCD_C
|
900 |
1090 |
1.4e-74 |
PFAM |
|
low complexity region
|
1113 |
1120 |
N/A |
INTRINSIC |
|
| Predicted Effect |
probably null
Transcript: ENSMUST00000125167
AA Change: L49*
|
| SMART Domains |
Protein: ENSMUSP00000124735
Gene: ENSMUSG00000039230
AA Change: L49*
| Domain | Start | End | E-Value | Type |
|---|
|
low complexity region
|
36 |
58 |
N/A |
INTRINSIC |
|
| Meta Mutation Damage Score |
0.9755 |
| Coding Region Coverage |
- 1x: 89.0%
- 3x: 85.6%
- 10x: 75.4%
- 20x: 57.8%
|
| Validation Efficiency |
94% (112/119) |
| MGI Phenotype |
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Cofactor D is one of four proteins (cofactors A, D, E, and C) involved in the pathway leading to correctly folded beta-tubulin from folding intermediates. Cofactors A and D are believed to play a role in capturing and stabilizing beta-tubulin intermediates in a quasi-native confirmation. Cofactor E binds to the cofactor D/beta-tubulin complex; interaction with cofactor C then causes the release of beta-tubulin polypeptides that are committed to the native state. [provided by RefSeq, Jul 2008]
|
| Allele List at MGI |
All alleles(23) : Gene trapped(23)
|
| Other mutations in this stock |
Total: 75 list
| Gene | Ref | Var | Chr/Loc | Mutation | Predicted Effect | Zygosity |
|---|
| 1810064F22Rik |
A |
G |
9: 22,119,177 (GRCm39) |
|
noncoding transcript |
Het |
| Aco2 |
T |
C |
15: 81,787,666 (GRCm39) |
|
probably benign |
Het |
| Arsa |
T |
A |
15: 89,358,539 (GRCm39) |
M288L |
possibly damaging |
Het |
| Atg2b |
A |
T |
12: 105,614,708 (GRCm39) |
D1074E |
probably benign |
Het |
| Baiap2l1 |
A |
T |
5: 144,221,372 (GRCm39) |
I174N |
probably damaging |
Het |
| Bptf |
A |
G |
11: 106,952,962 (GRCm39) |
V199A |
possibly damaging |
Het |
| Btn2a2 |
T |
A |
13: 23,662,655 (GRCm39) |
I432L |
probably benign |
Het |
| Ccdc150 |
A |
G |
1: 54,395,850 (GRCm39) |
I778V |
probably benign |
Het |
| Cd200r2 |
G |
A |
16: 44,730,037 (GRCm39) |
V194I |
possibly damaging |
Het |
| Cep350 |
A |
C |
1: 155,786,964 (GRCm39) |
L1421R |
probably damaging |
Het |
| Col6a6 |
A |
T |
9: 105,579,412 (GRCm39) |
C1938S |
probably damaging |
Het |
| Cspg4 |
A |
T |
9: 56,795,418 (GRCm39) |
D1051V |
probably damaging |
Het |
| Cstf1 |
T |
A |
2: 172,214,976 (GRCm39) |
N32K |
probably benign |
Het |
| Ctrb1 |
G |
A |
8: 112,413,269 (GRCm39) |
R248* |
probably null |
Het |
| Cyp2d11 |
T |
A |
15: 82,275,958 (GRCm39) |
M208L |
probably benign |
Het |
| Dbt |
A |
G |
3: 116,337,478 (GRCm39) |
Q334R |
probably benign |
Het |
| Dcaf12 |
A |
G |
4: 41,298,338 (GRCm39) |
V270A |
probably damaging |
Het |
| Dis3l |
T |
A |
9: 64,226,447 (GRCm39) |
N361I |
probably benign |
Het |
| Dnm3 |
A |
G |
1: 162,234,930 (GRCm39) |
V70A |
probably damaging |
Het |
| Dpy19l2 |
G |
A |
9: 24,557,679 (GRCm39) |
|
probably benign |
Het |
| Dst |
C |
A |
1: 34,228,634 (GRCm39) |
H2254N |
possibly damaging |
Het |
| Eif2b1 |
T |
G |
5: 124,711,858 (GRCm39) |
|
probably null |
Het |
| Epm2aip1 |
A |
G |
9: 111,101,531 (GRCm39) |
N168S |
probably benign |
Het |
| Fchsd2 |
A |
G |
7: 100,927,631 (GRCm39) |
Y691C |
possibly damaging |
Het |
| Fndc8 |
A |
T |
11: 82,788,398 (GRCm39) |
D76V |
probably benign |
Het |
| Frmd4a |
T |
C |
2: 4,477,963 (GRCm39) |
L48P |
probably damaging |
Het |
| Gimap6 |
T |
A |
6: 48,679,404 (GRCm39) |
I211F |
probably damaging |
Het |
| Gm15130 |
A |
G |
2: 110,969,284 (GRCm39) |
|
probably benign |
Het |
| Gm19618 |
A |
T |
6: 87,691,227 (GRCm39) |
|
|
Het |
| Gpatch1 |
G |
A |
7: 34,986,652 (GRCm39) |
S768L |
probably damaging |
Het |
| Grb14 |
T |
G |
2: 64,768,836 (GRCm39) |
|
probably null |
Het |
| Hnrnpd |
T |
C |
5: 100,112,560 (GRCm39) |
E222G |
probably damaging |
Het |
| Ighv1-4 |
A |
G |
12: 114,450,989 (GRCm39) |
S40P |
possibly damaging |
Het |
| Kcnh4 |
T |
C |
11: 100,648,626 (GRCm39) |
H26R |
probably benign |
Het |
| Kctd2 |
T |
G |
11: 115,320,343 (GRCm39) |
|
probably benign |
Het |
| Macf1 |
G |
A |
4: 123,325,943 (GRCm39) |
Q3066* |
probably null |
Het |
| Mfn2 |
G |
A |
4: 147,969,902 (GRCm39) |
|
probably benign |
Het |
| Mmab |
T |
C |
5: 114,574,526 (GRCm39) |
|
probably benign |
Het |
| Mrc1 |
T |
C |
2: 14,266,011 (GRCm39) |
S310P |
probably benign |
Het |
| Mrps21 |
T |
C |
3: 95,770,197 (GRCm39) |
Y44C |
probably null |
Het |
| Myh10 |
T |
A |
11: 68,590,317 (GRCm39) |
F121Y |
probably damaging |
Het |
| Myo1f |
A |
G |
17: 33,820,677 (GRCm39) |
D840G |
probably damaging |
Het |
| Nol6 |
G |
T |
4: 41,119,572 (GRCm39) |
|
probably benign |
Het |
| Ntsr2 |
T |
C |
12: 16,704,120 (GRCm39) |
I207T |
probably benign |
Het |
| Nwd1 |
T |
A |
8: 73,438,484 (GRCm39) |
S1552T |
probably benign |
Het |
| Or11j4 |
T |
A |
14: 50,630,659 (GRCm39) |
F149I |
probably benign |
Het |
| Pkd1l3 |
G |
T |
8: 110,347,103 (GRCm39) |
G159C |
unknown |
Het |
| Plcb4 |
T |
C |
2: 135,803,689 (GRCm39) |
S521P |
probably benign |
Het |
| Plcl1 |
A |
T |
1: 55,752,634 (GRCm39) |
I993F |
probably damaging |
Het |
| Plekha7 |
T |
C |
7: 115,756,743 (GRCm39) |
S640G |
probably damaging |
Het |
| Ptprn2 |
A |
C |
12: 117,240,222 (GRCm39) |
N993T |
probably benign |
Het |
| Reck |
A |
G |
4: 43,930,936 (GRCm39) |
N646D |
probably damaging |
Het |
| Rfx2 |
A |
T |
17: 57,093,736 (GRCm39) |
|
probably benign |
Het |
| Ripk2 |
G |
A |
4: 16,123,868 (GRCm39) |
Q436* |
probably null |
Het |
| Ryr1 |
C |
T |
7: 28,704,992 (GRCm39) |
|
probably benign |
Het |
| Sema6b |
A |
G |
17: 56,435,271 (GRCm39) |
V324A |
possibly damaging |
Het |
| Sik2 |
C |
A |
9: 50,909,833 (GRCm39) |
M73I |
probably benign |
Het |
| Slc39a6 |
T |
C |
18: 24,732,326 (GRCm39) |
K321E |
probably damaging |
Het |
| Slc7a4 |
C |
A |
16: 17,391,875 (GRCm39) |
V520F |
probably benign |
Het |
| Sptan1 |
C |
A |
2: 29,893,679 (GRCm39) |
|
probably benign |
Het |
| Stab1 |
C |
T |
14: 30,879,027 (GRCm39) |
|
probably benign |
Het |
| Tbc1d17 |
C |
T |
7: 44,493,495 (GRCm39) |
|
probably benign |
Het |
| Tulp4 |
A |
T |
17: 6,252,008 (GRCm39) |
N60I |
probably damaging |
Het |
| Ubqlnl |
A |
T |
7: 103,798,145 (GRCm39) |
W451R |
probably damaging |
Het |
| Usp53 |
G |
T |
3: 122,746,956 (GRCm39) |
C363* |
probably null |
Het |
| Utp4 |
A |
G |
8: 107,649,530 (GRCm39) |
T660A |
possibly damaging |
Het |
| Vmn1r194 |
A |
T |
13: 22,428,641 (GRCm39) |
Y86F |
probably benign |
Het |
| Vmn1r195 |
A |
T |
13: 22,463,409 (GRCm39) |
H293L |
possibly damaging |
Het |
| Vmn1r231 |
T |
C |
17: 21,109,998 (GRCm39) |
R306G |
probably benign |
Het |
| Vmn2r77 |
T |
C |
7: 86,449,964 (GRCm39) |
V70A |
probably benign |
Het |
| Vps8 |
A |
G |
16: 21,296,273 (GRCm39) |
E515G |
possibly damaging |
Het |
| Wdr18 |
C |
A |
10: 79,796,937 (GRCm39) |
Y104* |
probably null |
Het |
| Xab2 |
A |
T |
8: 3,663,880 (GRCm39) |
N346K |
probably damaging |
Het |
| Zdhhc12 |
C |
T |
2: 29,982,547 (GRCm39) |
R50H |
probably damaging |
Het |
| Zdhhc8 |
A |
G |
16: 18,043,064 (GRCm39) |
S379P |
probably benign |
Het |
|
| Other mutations in Tbcd |
| Allele | Source | Chr | Coord | Type | Predicted Effect | PPH Score |
|---|
|
IGL00519:Tbcd
|
APN |
11 |
121,466,147 (GRCm39) |
missense |
probably damaging |
0.96 |
|
IGL00795:Tbcd
|
APN |
11 |
121,507,758 (GRCm39) |
missense |
probably benign |
|
|
IGL00802:Tbcd
|
APN |
11 |
121,499,436 (GRCm39) |
missense |
possibly damaging |
0.55 |
|
IGL01286:Tbcd
|
APN |
11 |
121,384,719 (GRCm39) |
critical splice donor site |
probably null |
|
|
IGL01325:Tbcd
|
APN |
11 |
121,431,819 (GRCm39) |
missense |
probably damaging |
0.99 |
|
IGL01348:Tbcd
|
APN |
11 |
121,387,902 (GRCm39) |
missense |
probably benign |
|
|
IGL01432:Tbcd
|
APN |
11 |
121,366,506 (GRCm39) |
splice site |
probably benign |
|
|
IGL01577:Tbcd
|
APN |
11 |
121,387,838 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL01660:Tbcd
|
APN |
11 |
121,496,153 (GRCm39) |
missense |
probably benign |
0.01 |
|
IGL01865:Tbcd
|
APN |
11 |
121,481,206 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
IGL02260:Tbcd
|
APN |
11 |
121,494,104 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02492:Tbcd
|
APN |
11 |
121,387,960 (GRCm39) |
missense |
probably benign |
0.06 |
|
IGL02620:Tbcd
|
APN |
11 |
121,352,081 (GRCm39) |
missense |
probably damaging |
1.00 |
|
IGL02950:Tbcd
|
APN |
11 |
121,494,535 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R6859_Tbcd_818
|
UTSW |
11 |
121,387,937 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
R0066:Tbcd
|
UTSW |
11 |
121,394,590 (GRCm39) |
nonsense |
probably null |
|
|
R0077:Tbcd
|
UTSW |
11 |
121,485,100 (GRCm39) |
missense |
probably benign |
0.00 |
|
R0349:Tbcd
|
UTSW |
11 |
121,493,809 (GRCm39) |
splice site |
probably null |
|
|
R0865:Tbcd
|
UTSW |
11 |
121,493,815 (GRCm39) |
missense |
possibly damaging |
0.88 |
|
R1203:Tbcd
|
UTSW |
11 |
121,366,451 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1221:Tbcd
|
UTSW |
11 |
121,387,909 (GRCm39) |
missense |
probably benign |
0.00 |
|
R1549:Tbcd
|
UTSW |
11 |
121,451,579 (GRCm39) |
missense |
probably benign |
|
|
R1586:Tbcd
|
UTSW |
11 |
121,387,886 (GRCm39) |
missense |
probably benign |
0.13 |
|
R1671:Tbcd
|
UTSW |
11 |
121,488,120 (GRCm39) |
missense |
probably benign |
0.00 |
|
R2048:Tbcd
|
UTSW |
11 |
121,431,762 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2051:Tbcd
|
UTSW |
11 |
121,344,496 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2124:Tbcd
|
UTSW |
11 |
121,494,146 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R2151:Tbcd
|
UTSW |
11 |
121,494,457 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R2153:Tbcd
|
UTSW |
11 |
121,494,457 (GRCm39) |
missense |
possibly damaging |
0.95 |
|
R3120:Tbcd
|
UTSW |
11 |
121,499,474 (GRCm39) |
missense |
probably damaging |
0.97 |
|
R4108:Tbcd
|
UTSW |
11 |
121,384,637 (GRCm39) |
missense |
probably benign |
0.00 |
|
R4244:Tbcd
|
UTSW |
11 |
121,485,107 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4587:Tbcd
|
UTSW |
11 |
121,496,097 (GRCm39) |
missense |
possibly damaging |
0.75 |
|
R4684:Tbcd
|
UTSW |
11 |
121,384,597 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4837:Tbcd
|
UTSW |
11 |
121,473,611 (GRCm39) |
critical splice donor site |
probably null |
|
|
R4861:Tbcd
|
UTSW |
11 |
121,492,787 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4861:Tbcd
|
UTSW |
11 |
121,492,787 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R4960:Tbcd
|
UTSW |
11 |
121,464,681 (GRCm39) |
missense |
probably benign |
0.03 |
|
R5157:Tbcd
|
UTSW |
11 |
121,500,853 (GRCm39) |
missense |
probably benign |
0.14 |
|
R5166:Tbcd
|
UTSW |
11 |
121,500,216 (GRCm39) |
missense |
possibly damaging |
0.87 |
|
R5403:Tbcd
|
UTSW |
11 |
121,451,569 (GRCm39) |
missense |
probably damaging |
0.99 |
|
R5406:Tbcd
|
UTSW |
11 |
121,342,927 (GRCm39) |
missense |
probably benign |
|
|
R5509:Tbcd
|
UTSW |
11 |
121,492,838 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5767:Tbcd
|
UTSW |
11 |
121,483,518 (GRCm39) |
missense |
probably benign |
0.00 |
|
R5923:Tbcd
|
UTSW |
11 |
121,470,978 (GRCm39) |
missense |
probably benign |
|
|
R5966:Tbcd
|
UTSW |
11 |
121,492,737 (GRCm39) |
intron |
probably benign |
|
|
R6330:Tbcd
|
UTSW |
11 |
121,387,912 (GRCm39) |
missense |
probably benign |
|
|
R6539:Tbcd
|
UTSW |
11 |
121,447,813 (GRCm39) |
critical splice donor site |
probably null |
|
|
R6852:Tbcd
|
UTSW |
11 |
121,500,206 (GRCm39) |
missense |
probably benign |
0.36 |
|
R6859:Tbcd
|
UTSW |
11 |
121,387,937 (GRCm39) |
missense |
possibly damaging |
0.81 |
|
R7348:Tbcd
|
UTSW |
11 |
121,485,137 (GRCm39) |
missense |
probably benign |
0.22 |
|
R7479:Tbcd
|
UTSW |
11 |
121,383,431 (GRCm39) |
critical splice donor site |
probably null |
|
|
R7679:Tbcd
|
UTSW |
11 |
121,494,534 (GRCm39) |
missense |
probably benign |
0.01 |
|
R8121:Tbcd
|
UTSW |
11 |
121,487,969 (GRCm39) |
splice site |
probably null |
|
|
R8163:Tbcd
|
UTSW |
11 |
121,384,711 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8165:Tbcd
|
UTSW |
11 |
121,384,711 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8172:Tbcd
|
UTSW |
11 |
121,384,711 (GRCm39) |
missense |
probably benign |
0.00 |
|
R8973:Tbcd
|
UTSW |
11 |
121,387,679 (GRCm39) |
unclassified |
probably benign |
|
|
R8975:Tbcd
|
UTSW |
11 |
121,387,679 (GRCm39) |
unclassified |
probably benign |
|
|
R9314:Tbcd
|
UTSW |
11 |
121,487,297 (GRCm39) |
missense |
probably benign |
0.01 |
|
R9345:Tbcd
|
UTSW |
11 |
121,464,648 (GRCm39) |
missense |
probably damaging |
1.00 |
|
R9556:Tbcd
|
UTSW |
11 |
121,467,053 (GRCm39) |
missense |
probably damaging |
0.96 |
|
R9673:Tbcd
|
UTSW |
11 |
121,464,647 (GRCm39) |
missense |
probably damaging |
1.00 |
|
Z1177:Tbcd
|
UTSW |
11 |
121,481,232 (GRCm39) |
missense |
probably null |
0.14 |
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| Protein Function and Prediction |
Tbcd encodes tubulin folding cofactor D (TBCD), a member of the tubulin synthesis complex (1). TBCD modulates microtubule dynamics by sequestering β-tubulin from GTP-bound αβ-heterodimers (2). Fanarraga et al. determined that TBCD has a role in centriologenesis, spindle organization, and cell abcission (1). TBCD depletion results in mitotic aberrations and incomplete microtubule retraction at the midbody during cytokinesis (1). Human TBCD is proposed to recruite cytosolic centrosomal proteins (e.g., pericentrin or γ-tubulin) to the mitotic spindle (3). Mutations in TBCD have been linked to chromosome number aberrations, G1/S blockage, spindle pole body separation, and abnormal cytokinesis in yeast, Arabidopsis, and Caenorhabditis elegans (4-10). TBCD is ubiquitously expressed in human tissues tested (i.e., brain, spinal cord, liver, pancreas, kidney, spleen, heart, lung, skeletal muscle, testis, ovary, fetal brain, and fetal liver) by RT-PCR followed by ELISA (11). The TBCD protein is localized throughout the cell (2). Further studies determined that TBCD is concentrated at the centrosome and midbody (1). Furthermore, TBCD localization is cell-cycle-specific with localization on the daughter centriole at G1 and on procentrioles by S; TBCD disappears from older centrioles at telophase as the protein is recruited to the midbody (1). At the onset of the centrosome duplication cycle, TBCD is recruited to the centriole replication site (1). During cytokinesis TBCD is localized at Fleming bodies at the midbody (1).
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| References |
1. Fanarraga, M. L., Bellido, J., Jaen, C., Villegas, J. C., and Zabala, J. C. (2010) TBCD Links Centriologenesis, Spindle Microtubule Dynamics, and Midbody Abscission in Human Cells. PLoS One. 5, e8846.
6. Sonnichsen, B., Koski, L. B., Walsh, A., Marschall, P., Neumann, B., Brehm, M., Alleaume, A. M., Artelt, J., Bettencourt, P., Cassin, E., Hewitson, M., Holz, C., Khan, M., Lazik, S., Martin, C., Nitzsche, B., Ruer, M., Stamford, J., Winzi, M., Heinkel, R., Roder, M., Finell, J., Hantsch, H., Jones, S. J., Jones, M., Piano, F., Gunsalus, K. C., Oegema, K., Gonczy, P., Coulson, A., Hyman, A. A., and Echeverri, C. J. (2005) Full-Genome RNAi Profiling of Early Embryogenesis in Caenorhabditis Elegans. Nature. 434, 462-469.
8. Fedyanina, O. S., Mardanov, P. V., Tokareva, E. M., McIntosh, J. R., and Grishchuk, E. L. (2006) Chromosome Segregation in Fission Yeast with Mutations in the Tubulin Folding Cofactor D. Curr Genet. 50, 281-294.
9. Steinborn, K., Maulbetsch, C., Priester, B., Trautmann, S., Pacher, T., Geiges, B., Kuttner, F., Lepiniec, L., Stierhof, Y. D., Schwarz, H., Jurgens, G., and Mayer, U. (2002) The Arabidopsis PILZ Group Genes Encode Tubulin-Folding Cofactor Orthologs Required for Cell Division but Not Cell Growth. Genes Dev. 16, 959-971.
11. Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., and Ohara, O. (1999) Prediction of the Coding Sequences of Unidentified Human Genes. XIII. the Complete Sequences of 100 New cDNA Clones from Brain which Code for Large Proteins in Vitro. DNA Res. 6, 63-70.
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| Posted On |
2013-01-20 |
| Science Writer |
Anne Murray |
Incidental Mutation