CEP57

Chr 11

centrosomal protein 57

Also known as: MVA2, PIG8, TSP57

This gene encodes a cytoplasmic protein called Translokin. This protein localizes to the centrosome and has a function in microtubular stabilization. The N-terminal half of this protein is required for its centrosome localization and for its multimerization, and the C-terminal half is required for nucleating, bundling and anchoring microtubules to the centrosomes. This protein specifically interacts with fibroblast growth factor 2 (FGF2), sorting nexin 6, Ran-binding protein M and the kinesins KIF3A and KIF3B, and thus mediates the nuclear translocation and mitogenic activity of the FGF2. It also interacts with cyclin D1 and controls nucleocytoplasmic distribution of the cyclin D1 in quiescent cells. This protein is crucial for maintaining correct chromosomal number during cell division. Mutations in this gene cause mosaic variegated aneuploidy syndrome, a rare autosomal recessive disorder. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

ResearchGenerating clinical summary…
LOFmechanismLOEUF 0.48
Clinical SummaryCEP57
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Gene-Disease Validity (ClinGen)
mosaic variegated aneuploidy syndrome 2 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
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ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 592 VUS of 928 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.48LOEUF
pLI 0.073
Z-score 3.72
OE 0.27 (0.150.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
-0.46Z-score
OE missense 1.08 (0.981.19)
277 obs / 256.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.27 (0.150.48)
00.351.4
Missense OE?1.08 (0.981.19)
00.61.4
Synonymous OE?1.12
01.21.6
LoF obs/exp: 8 / 30.0Missense obs/exp: 277 / 256.4Syn Z: -0.93
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCEP57-related mosaic variegated aneuploidy syndromeLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7326th %ile
GOF
0.5856th %ile
LOF
0.3842th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

928 submitted variants in ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic6
VUS592
Likely Benign282
Benign8
Conflicting13
15
Pathogenic
6
Likely Pathogenic
592
VUS
282
Likely Benign
8
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
0
1
0
15
Likely Pathogenic
5
0
1
0
6
VUS
9
554
25
4
592
Likely Benign
0
11
60
211
282
Benign
0
2
4
2
8
Conflicting
13
Total2856791217916

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

15 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap CEP57 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

CEP57 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →