CCNA1

Chr 13

cyclin A1

Also known as: CT146

NCBI Gene: 8900 ENSG00000133101 UniProt: P78396

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.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. The cyclin encoded by this gene was shown to be expressed in testis and brain, as well as in several leukemic cell lines, and is thought to primarily function in the control of the germline meiotic cell cycle. This cyclin binds both CDK2 and CDC2 kinases, which give two distinct kinase activities, one appearing in S phase, the other in G2, and thus regulate separate functions in cell cycle. This cyclin was found to bind to important cell cycle regulators, such as Rb family proteins, transcription factor E2F-1, and the p21 family proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.68

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.68LOEUF

pLI 0.000

Z-score 2.77

OE 0.40 (0.25–0.68)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.25Z-score

OE missense 0.78 (0.69–0.88)

193 obs / 248.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.25–0.68)

0≤0.351.4

Missense OE?0.78 (0.69–0.88)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 10 / 24.9Missense obs/exp: 193 / 248.5Syn Z: -0.46

Background carrier burden — how many people carry a rare variant somewhere in CCNA1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

479 rare PASS variants

Rare truncating (LoF)

1 in 2,300

55 rare PASS variants

Rare synonymous (reference)

1 in 120

229 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CCNA1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 7,000
South Asian	~43k	1 in 150	1 in 2,300
Remaining (unassigned)	~30k	1 in 100	1 in 5,000
European (Finnish)	~27k	1 in 370	1 in 5,300
Admixed American	~22k	1 in 120	≈ 1 in 4,500
African / African American	~21k	1 in 210	1 in 1,800
East Asian	~20k	1 in 220	1 in 2,000
Ashkenazi Jewish	~13k	1 in 1,000	1 in 1,900
Middle Eastern	~2,884	1 in 100	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 8 coding exons well covered in gnomAD exomes; exon 7 marginal. Genomes: all 8.? see exons ↓