Incidental Mutation 'IGL00795:Tbcd'
ID14389
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Tbcd
Ensembl Gene ENSMUSG00000039230
Gene Nametubulin-specific chaperone d
Synonyms2310057L06Rik, A030005L14Rik
Accession Numbers

Ncbi RefSeq: NM_029878.3; MGI:1919686

Is this an essential gene? Probably essential (E-score: 0.959) question?
Stock #IGL00795
Quality Score
Status
Chromosome11
Chromosomal Location121451949-121617164 bp(+) (GRCm38)
Type of Mutationmissense
DNA Base Change (assembly) T to G at 121616932 bp
ZygosityHeterozygous
Amino Acid Change Isoleucine to Serine at position 1193 (I1193S)
Ref Sequence ENSEMBL: ENSMUSP00000099302 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000067399] [ENSMUST00000103013]
Predicted Effect probably benign
Transcript: ENSMUST00000067399
SMART Domains Protein: ENSMUSP00000068590
Gene: ENSMUSG00000046605

DomainStartEndE-ValueType
Pfam:Glyco_tranf_2_3 14 245 1.4e-10 PFAM
Pfam:Glycos_transf_2 17 189 1.2e-23 PFAM
Pfam:Glyco_tranf_2_2 17 248 2.1e-8 PFAM
Predicted Effect probably benign
Transcript: ENSMUST00000103013
AA Change: I1193S

PolyPhen 2 Score 0.000 (Sensitivity: 1.00; Specificity: 0.00)
SMART Domains Protein: ENSMUSP00000099302
Gene: ENSMUSG00000039230
AA Change: I1193S

DomainStartEndE-ValueType
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 noncoding transcript
Transcript: ENSMUST00000139414
Predicted Effect noncoding transcript
Transcript: ENSMUST00000151666
Predicted Effect noncoding transcript
Transcript: ENSMUST00000155666
Coding Region Coverage
Validation Efficiency
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: 15 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
5031410I06Rik T C 5: 26,104,155 R50G probably damaging Het
Ap1m1 A G 8: 72,253,509 N308S probably damaging Het
Bub1 A G 2: 127,821,815 V222A probably benign Het
Ccdc91 G T 6: 147,507,807 D4Y probably damaging Het
Defb21 A G 2: 152,574,745 D47G probably benign Het
Dnah17 C A 11: 118,093,634 C1607F probably benign Het
Fam126b C T 1: 58,552,179 E102K probably damaging Het
Insc T C 7: 114,842,154 L401P probably damaging Het
Kif18a A T 2: 109,293,020 N213I probably damaging Het
Mapre1 A G 2: 153,746,314 D19G probably damaging Het
Mettl8 A T 2: 70,982,090 I32N probably damaging Het
Mroh9 T A 1: 163,060,622 T295S probably damaging Het
Pum3 T A 19: 27,422,358 Y225F probably damaging Het
Tas2r131 G A 6: 132,957,591 T85I possibly damaging Het
Tgoln1 C T 6: 72,616,252 A82T probably benign Het
Other mutations in Tbcd
AlleleSourceChrCoordTypePredicted EffectPPH Score
IGL00519:Tbcd APN 11 121575321 missense probably damaging 0.96
IGL00802:Tbcd APN 11 121608610 missense possibly damaging 0.55
IGL01286:Tbcd APN 11 121493893 critical splice donor site probably null
IGL01325:Tbcd APN 11 121540993 missense probably damaging 0.99
IGL01348:Tbcd APN 11 121497076 missense probably benign
IGL01432:Tbcd APN 11 121475680 splice site probably benign
IGL01577:Tbcd APN 11 121497012 missense probably damaging 1.00
IGL01660:Tbcd APN 11 121605327 missense probably benign 0.01
IGL01865:Tbcd APN 11 121590380 missense possibly damaging 0.81
IGL02260:Tbcd APN 11 121603278 missense probably damaging 1.00
IGL02492:Tbcd APN 11 121497134 missense probably benign 0.06
IGL02620:Tbcd APN 11 121461255 missense probably damaging 1.00
IGL02950:Tbcd APN 11 121603709 missense probably damaging 0.99
R6859_Tbcd_818 UTSW 11 121497111 missense possibly damaging 0.81
R0066:Tbcd UTSW 11 121503764 nonsense probably null
R0066:Tbcd UTSW 11 121503764 nonsense probably null
R0077:Tbcd UTSW 11 121594274 missense probably benign 0.00
R0349:Tbcd UTSW 11 121602983 splice site probably null
R0865:Tbcd UTSW 11 121602989 missense possibly damaging 0.88
R1203:Tbcd UTSW 11 121475625 missense probably benign 0.00
R1221:Tbcd UTSW 11 121497083 missense probably benign 0.00
R1549:Tbcd UTSW 11 121560753 missense probably benign
R1586:Tbcd UTSW 11 121497060 missense probably benign 0.13
R1671:Tbcd UTSW 11 121597294 missense probably benign 0.00
R2048:Tbcd UTSW 11 121540936 missense probably damaging 1.00
R2051:Tbcd UTSW 11 121453670 missense probably damaging 1.00
R2124:Tbcd UTSW 11 121603320 missense probably damaging 1.00
R2151:Tbcd UTSW 11 121603631 missense possibly damaging 0.95
R2153:Tbcd UTSW 11 121603631 missense possibly damaging 0.95
R3120:Tbcd UTSW 11 121608648 missense probably damaging 0.97
R4108:Tbcd UTSW 11 121493811 missense probably benign 0.00
R4244:Tbcd UTSW 11 121594281 missense probably damaging 1.00
R4587:Tbcd UTSW 11 121605271 missense possibly damaging 0.75
R4684:Tbcd UTSW 11 121493771 missense probably damaging 1.00
R4837:Tbcd UTSW 11 121582785 critical splice donor site probably null
R4861:Tbcd UTSW 11 121601961 missense probably damaging 1.00
R4861:Tbcd UTSW 11 121601961 missense probably damaging 1.00
R4960:Tbcd UTSW 11 121573855 missense probably benign 0.03
R5157:Tbcd UTSW 11 121610027 missense probably benign 0.14
R5166:Tbcd UTSW 11 121609390 missense possibly damaging 0.87
R5403:Tbcd UTSW 11 121560743 missense probably damaging 0.99
R5406:Tbcd UTSW 11 121452101 missense probably benign
R5509:Tbcd UTSW 11 121602012 missense probably benign 0.00
R5767:Tbcd UTSW 11 121592692 missense probably benign 0.00
R5923:Tbcd UTSW 11 121580152 missense probably benign
R5966:Tbcd UTSW 11 121601911 intron probably benign
R6330:Tbcd UTSW 11 121497086 missense probably benign
R6539:Tbcd UTSW 11 121556987 critical splice donor site probably null
R6852:Tbcd UTSW 11 121609380 missense probably benign 0.36
R6859:Tbcd UTSW 11 121497111 missense possibly damaging 0.81
R7348:Tbcd UTSW 11 121594311 missense probably benign 0.22
R7479:Tbcd UTSW 11 121492605 critical splice donor site probably null
R7679:Tbcd UTSW 11 121603708 missense probably benign 0.01
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).

References
  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.
Posted On2012-12-06
Science WriterAnne Murray