CCNA1

Chr 13

cyclin A1

Also known as: CT146

CCNA1 encodes cyclin A1, which regulates cell cycle transitions at G1/S and G2/M phases by binding and activating CDK2 and CDC2 kinases, with primary functions in germline meiotic cell cycle control and some roles in somatic cell mitosis. Mutations cause autosomal recessive primary male infertility due to meiotic arrest during spermatogenesis. The gene shows low constraint against loss-of-function variants (pLI 0.0004, LOEUF 0.68), consistent with its tissue-specific expression pattern primarily affecting reproductive function.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.68
Clinical SummaryCCNA1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
49 unique Pathogenic / Likely Pathogenic· 62 VUS of 133 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.68LOEUF
pLI 0.000
Z-score 2.77
OE 0.40 (0.250.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.25Z-score
OE missense 0.78 (0.690.88)
193 obs / 248.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.40 (0.250.68)
00.351.4
Missense OE0.78 (0.690.88)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 10 / 24.9Missense obs/exp: 193 / 248.5Syn Z: -0.46
DN
0.73top 25%
GOF
0.5170th %ile
LOF
0.3162th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

133 submitted variants in ClinVar

Classification Summary

Pathogenic49
VUS62
Likely Benign5
Benign4
49
Pathogenic
62
VUS
5
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
49
0
49
Likely Pathogenic
0
0
0
0
0
VUS
0
41
21
0
62
Likely Benign
0
1
2
2
5
Benign
0
0
1
3
4
Total042735120

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

View in ClinVar →

Protein Context — Lollipop Plot

CCNA1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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