Incidental Mutation 'IGL00519:Tbcd'
ID 5997
Institutional Source Australian Phenomics Network (link to record)
Gene Symbol Tbcd
Ensembl Gene ENSMUSG00000039230
Gene Name tubulin-specific chaperone d
Synonyms 2310057L06Rik, A030005L14Rik
Accession Numbers
Essential gene? Probably essential (E-score: 0.957) question?
Stock # IGL00519
Quality Score
Status
Chromosome 11
Chromosomal Location 121342817-121507996 bp(+) (GRCm39)
Type of Mutation missense
DNA Base Change (assembly) A to G at 121466147 bp (GRCm39)
Zygosity Heterozygous
Amino Acid Change Asparagine to Serine at position 591 (N591S)
Ref Sequence ENSEMBL: ENSMUSP00000099302 (fasta)
Gene Model predicted gene model for transcript(s): [ENSMUST00000103013]
AlphaFold Q8BYA0
Predicted Effect probably damaging
Transcript: ENSMUST00000103013
AA Change: N591S

PolyPhen 2 Score 0.957 (Sensitivity: 0.78; Specificity: 0.95)
SMART Domains Protein: ENSMUSP00000099302
Gene: ENSMUSG00000039230
AA Change: N591S

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 probably benign
Transcript: ENSMUST00000125167
SMART Domains Protein: ENSMUSP00000124735
Gene: ENSMUSG00000039230

DomainStartEndE-ValueType
low complexity region 36 58 N/A INTRINSIC
Predicted Effect noncoding transcript
Transcript: ENSMUST00000147470
Predicted Effect noncoding transcript
Transcript: ENSMUST00000147560
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: 25 list
GeneRefVarChr/LocMutationPredicted EffectZygosity
Adam26a A T 8: 44,022,562 (GRCm39) N309K probably damaging Het
Asap1 G A 15: 63,982,791 (GRCm39) P846S probably damaging Het
Atg10 A G 13: 91,302,330 (GRCm39) probably benign Het
Cdk18 C A 1: 132,043,226 (GRCm39) R433L probably benign Het
Celsr1 A G 15: 85,915,037 (GRCm39) Y979H probably damaging Het
Cracr2b T C 7: 141,045,670 (GRCm39) probably benign Het
Csmd2 T C 4: 128,377,266 (GRCm39) F2049L probably benign Het
Cubn T C 2: 13,287,730 (GRCm39) N3450D probably benign Het
Dmrt1 T C 19: 25,580,638 (GRCm39) L350P probably damaging Het
Dnah5 A T 15: 28,444,364 (GRCm39) D4054V probably benign Het
Dpp8 A T 9: 64,985,290 (GRCm39) T783S probably damaging Het
Enpp3 T C 10: 24,663,670 (GRCm39) T564A probably benign Het
Exoc6b T C 6: 84,966,435 (GRCm39) K180E probably benign Het
Faf1 T A 4: 109,697,578 (GRCm39) F301L probably benign Het
Fbxo7 A T 10: 85,864,928 (GRCm39) E77V probably damaging Het
Gabpa T G 16: 84,657,489 (GRCm39) *455G probably null Het
Hexim2 A T 11: 103,024,905 (GRCm39) M1L probably benign Het
Lrrc24 T A 15: 76,602,263 (GRCm39) N164I probably damaging Het
Lrrc8b G A 5: 105,629,591 (GRCm39) A646T possibly damaging Het
Mansc1 T A 6: 134,587,769 (GRCm39) Q136L possibly damaging Het
Mlxip T A 5: 123,585,268 (GRCm39) V592E probably benign Het
Ncor2 T C 5: 125,161,988 (GRCm39) T429A unknown Het
Tenm4 T C 7: 96,454,345 (GRCm39) probably benign Het
Uri1 A G 7: 37,660,978 (GRCm39) S522P probably damaging Het
Ush2a C T 1: 188,176,865 (GRCm39) S1343L probably benign Het
Other mutations in Tbcd
AlleleSourceChrCoordTypePredicted EffectPPH Score
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
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
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 On 2012-04-20
Science Writer Anne Murray