CDCA3

Chr 12

cell division cycle associated 3

Also known as: GRCC8, TOME-1, TOME1

CDCA3 encodes an F-box-like protein required for mitotic entry that participates in E3 ligase complexes mediating ubiquitination and degradation of WEE1 kinase during the G2/M phase of cell division. Mutations cause autosomal recessive primary microcephaly with growth retardation and intellectual disability. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.504), consistent with its essential role in cell cycle regulation.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
26
Pubs (1 yr)
46
P/LP submissions
2%
P/LP missense
0.50
LOEUF
Mechanism
Clinical SummaryCDCA3
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.69) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
46 unique Pathogenic / Likely Pathogenic· 111 VUS of 209 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.50LOEUF
pLI 0.688
Z-score 2.75
OE 0.16 (0.060.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.66Z-score
OE missense 0.85 (0.730.98)
127 obs / 149.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.16 (0.060.50)
00.351.4
Missense OE0.85 (0.730.98)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 2 / 12.5Missense obs/exp: 127 / 149.6Syn Z: 0.89

ClinVar Variant Classifications

209 submitted variants in ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic2
VUS111
Likely Benign29
Benign13
Conflicting1
44
Pathogenic
2
Likely Pathogenic
111
VUS
29
Likely Benign
13
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
43
0
44
Likely Pathogenic
0
0
2
0
2
VUS
4
91
16
0
111
Likely Benign
0
6
9
14
29
Benign
0
1
7
5
13
Conflicting
1
Total4997719200

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

View in ClinVar →

Protein Context — Lollipop Plot

CDCA3 · 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.

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Clinical Literature
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