CCNA2

Chr 4

cyclin A2

Also known as: CCN1, CCNA

Cyclin A2 is a cell cycle regulatory protein that binds and activates cyclin-dependent kinases CDK1 and CDK2 to control the G1/S and G2/M cell cycle transitions. Mutations cause microcephaly, short stature, and intellectual disability with autosomal recessive inheritance. This gene is highly constrained against loss-of-function variants in the population.

Summary from RefSeq, UniProt
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1
Active trials
141
Pubs (1 yr)
21
P/LP submissions
0%
P/LP missense
0.13
LOEUF· LoF intol.
LOF
Mechanism· G2P
Clinical SummaryCCNA2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
21 unique Pathogenic / Likely Pathogenic· 43 VUS of 88 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.13LOEUF
pLI 1.000
Z-score 4.41
OE 0.00 (0.000.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.22Z-score
OE missense 0.59 (0.510.68)
136 obs / 230.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.13)
00.351.4
Missense OE0.59 (0.510.68)
00.61.4
Synonymous OE0.91
01.21.6
LoF obs/exp: 0 / 22.6Missense obs/exp: 136 / 230.9Syn Z: 0.65
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCCNA2-related intellectual developmental disorderLOFAR

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

DN
0.3892th %ile
GOF
0.3292th %ile
LOF
0.70top 10%

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

88 submitted variants in ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic1
VUS43
Likely Benign5
Benign7
20
Pathogenic
1
Likely Pathogenic
43
VUS
5
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
20
0
20
Likely Pathogenic
0
0
1
0
1
VUS
3
28
12
0
43
Likely Benign
0
3
2
0
5
Benign
0
2
3
2
7
Total33338276

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

View in ClinVar →

Protein Context — Lollipop Plot

CCNA2 · protein map & ClinVar variants

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

Clinical Literature
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