CEP57 (centrosomal protein 57kDa)

2011-12-01   Sandra Hanks , Katie Snape , Nazneen Rahman 

Institute of Cancer Research, Division of Genetics, Epidemiology, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK

Identity

HGNC
LOCATION
11q21
LOCUSID
ALIAS
MVA2,PIG8,TSP57
FUSION GENES

DNA/RNA

Atlas Image
Figure 1. Schematic representation of CEP57 demonstrating the relative exon sizes.

Description

CEP57 spans over 42 kb and is composed of 11 exons.

Proteins

Atlas Image
Figure 2. Schematic representation of CEP57 demonstrating significant functional or structural domains.

Description

500 amino acids, 57 kDa.

Expression

Ubiquituously expressed.

Localisation

Nucleus, cytoplasm, cytoskeleton, centrosome.

Function

Centrosomal protein required for microtubule attachment to centrosomes. Also involved in intracellular bidirectional trafficking of factors such as FGF2 along microtubules.

Homology

The CEP57 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, and zebrafish.

Mutations

Atlas Image
Figure 3. Schematic representation of CEP57 demonstrating the relative exon sizes and positions of known mutations. Biallelic mutations are represented by coloured lines, with mutations in the same individual in matching colours.

Germinal

Biallelic, loss-of-function mutations in CEP57 have been found in three MVA pedigrees (figure 3).

Implicated in

Entity name
Mosaic variegated aneuploidy syndrome (MVA)
Note
MVA is a rare recessive condition characterised by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. Affected individuals typically present with severe intrauterine growth retardation and microcephaly. Eye anomalies, mild dysmorphism, variable developmental delay and a broad spectrum of additional congenital abnormalities and medical conditions may also occur.
Prognosis
The prognosis for an individual with MVA syndrome is based on the malformations present in the individual. There is early mortality in a significant proportion of cases due to failure to thrive and/or complications of congenital abnormalities, epilepsy, infections or malignancy.
Cytogenetics
MVA is characterised by mosaic aneuploidies, predominantly trisomies and monosomies, involving multiple different chromosomes and tissues. The proportion of aneuploid cells varies but is usually >10% and is substantially greater than in normal individuals. Some patients with MVA also demonstrate premature chromatid separation in colchicine-treated blood lymphocyte and fibroblast cultures.
Oncogenesis
The risk of malignancy in MVA is high with Wilms tumour, rhabdomyosarcoma, leukaemia and granulosa cell tumour of the ovary reported in several cases. Myelodysplastic syndrome has also been observed.

Bibliography

Pubmed IDLast YearTitleAuthors
185485312008Clinical and genetic heterogeneity in patients with mosaic variegated aneuploidy: delineation of clinical subtypes.García-Castillo H et al
154759552004Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B.Hanks S et al
121162372002Mosaic variegated aneuploidy with growth hormone deficiency and congenital heart defects.Lane AH et al
164112012006Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome.Matsuura S et al
198045662009Pivotal role of translokin/CEP57 in the unconventional secretion versus nuclear translocation of FGF2.Meunier S et al
182941412008Cep57, a multidomain protein with unique microtubule and centrosomal localization domains.Momotani K et al
215522662011Mutations in CEP57 cause mosaic variegated aneuploidy syndrome.Snape K et al

Other Information

Locus ID:

NCBI: 9702
MIM: 607951
HGNC: 30794
Ensembl: ENSG00000166037

Variants:

dbSNP: 9702
ClinVar: 9702
TCGA: ENSG00000166037
COSMIC: CEP57

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000166037ENST00000325486Q86XR8
ENSG00000166037ENST00000325542Q86XR8
ENSG00000166037ENST00000535224H0YFT8
ENSG00000166037ENST00000535497F5H7J4
ENSG00000166037ENST00000537093H0YGT4
ENSG00000166037ENST00000537677F5GYW0
ENSG00000166037ENST00000538095F5GZ93
ENSG00000166037ENST00000538658Q86XR8
ENSG00000166037ENST00000539855F5H6R3
ENSG00000166037ENST00000540830F5GXS6
ENSG00000166037ENST00000541150Q86XR8
ENSG00000166037ENST00000541365F5H1B0
ENSG00000166037ENST00000544522F5H0C6

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45
50

Pathways

PathwaySourceExternal ID
Organelle biogenesis and maintenanceREACTOMER-HSA-1852241
Cilium AssemblyREACTOMER-HSA-5617833
Anchoring of the basal body to the plasma membraneREACTOMER-HSA-5620912
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
Mitotic G2-G2/M phasesREACTOMER-HSA-453274
G2/M TransitionREACTOMER-HSA-69275
Regulation of PLK1 Activity at G2/M TransitionREACTOMER-HSA-2565942
Centrosome maturationREACTOMER-HSA-380287
Recruitment of mitotic centrosome proteins and complexesREACTOMER-HSA-380270
Loss of proteins required for interphase microtubule organization from the centrosomeREACTOMER-HSA-380284
Loss of Nlp from mitotic centrosomesREACTOMER-HSA-380259
AURKA Activation by TPX2REACTOMER-HSA-8854518

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
215522662011Mutations in CEP57 cause mosaic variegated aneuploidy syndrome.47
233333162013Selective chemical crosslinking reveals a Cep57-Cep63-Cep152 centrosomal complex.39
225082652012Cep57, a NEDD1-binding pericentriolar material component, is essential for spindle pole integrity.13
206280862010Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.11
232430192013FGF-2 disrupts mitotic stability in prostate cancer through the intracellular trafficking protein CEP57.10
267439402016Cep57 is a Mis12-interacting kinetochore protein involved in kinetochore targeting of Mad1-Mad2.10
235692072013Cep57 protein is required for cytokinesis by facilitating central spindle microtubule organization.5
308043442019The Cep57-pericentrin module organizes PCM expansion and centriole engagement.5
265610352015Copy number variation in CEP57L1 predisposes to congenital absence of bilateral ACL and PCL ligaments.3

Citation

Sandra Hanks ; Katie Snape ; Nazneen Rahman

CEP57 (centrosomal protein 57kDa)

Atlas Genet Cytogenet Oncol Haematol. 2011-12-01

Online version: http://atlasgeneticsoncology.org/gene/43008/cep57