CCNA2

protein-coding

cyclin A2, the group of Cyclins

Gene summary

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members function as regulators of the cell cycle. This protein binds and activates cyclin-dependent kinase 2 and thus promotes transition through G1/S and G2/M. [provided by RefSeq, Aug 2016]

Previous symbols:

CCNA
CCN1

MANE transcript

NM_001237.5

Inheritance

ClinVar variants

U:29B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr4:121,816,444-121,823,883

External References & Databases

Ensembl (ENSG00000145386)

Transcript & Mutation Effects

hg38 • Region Span ~7.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CCNA2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 30

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001237.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar	2 clinvar	5
missense			28 clinvar	3 clinvar	1 clinvar	32
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	29	6	3	38

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001237.5	RefSeq	NP_001228.2	8	MANE Select
ENST00000274026.10	Ensembl	ENSP00000274026.5	8	MANE Select
ENST00000876644.1	Ensembl	ENSP00000546703.1	8	Standard
ENST00000876644.2	Ensembl	ENSP00000546703.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ccna2	Danio rerio	Structure: head Quality: pointed abnormal

Gene / Model

Organism

Observed Phenotype

ccna2

Danio rerio

Structure: head

Quality: pointed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell cycle - Homo sapiens (human)
AMPK signaling pathway - Homo sapiens (human)
Viral carcinogenesis - Homo sapiens (human)
Hepatitis B - Homo sapiens (human)
Cellular senescence - Homo sapiens (human)

Biological Process

regulation of cyclin-dependent protein serine/threonine kinase activity
G2/M transition of mitotic cell cycle
mitotic cell cycle
regulation of DNA replication
regulation of mitotic nuclear division

Molecular Function

protein kinase activity
protein binding
cyclin-dependent protein serine/threonine kinase regulator activity
protein kinase binding
protein domain specific binding

Cellular Component

cyclin-dependent protein kinase holoenzyme complex
female pronucleus
male pronucleus
nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000274026
Coding exons: 8
Length: 7489
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125738
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.22	136	231	0.589	0.0000106	2801
Missense (PolyPhen)		17	58.778	0.28922		774
Synonymous	0.649	82	89.8	0.913	0.00000424	845
Loss of Function	4.41	0	22.6	0.00	0.00000115	274

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000061	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cyclin which controls both the G1/S and the G2/M transition phases of the cell cycle. Functions through the formation of specific serine/threonine protein kinase holoenzyme complexes with the cyclin-dependent protein kinases CDK1 or CDK2. The cyclin subunit confers the substrate specificity of these complexes and differentially interacts with and activates CDK1 and CDK2 throughout the cell cycle. {ECO:0000269|PubMed:1312467}.;

Recessive Scores

pRec: 0.522

Intolerance Scores

LoFtool: 0.0958
RVIS EVS: 0.37
RVIS percentile EVS: 75.12

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.758

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium