DNA size: 40200 bp, DNA linear, on reverse strand. This gene has 6 transcripts (splice variants), 412 orthologues, 2 paralogues and is a member of 1 Ensembl protein family.

CSNK2A2-201 ENST00000262506.8: mRNA 1887 bp, protein 350 aa
CSNK2A2-202 ENST00000562367.1: mRNA 687 bp, No protein
CSNK2A2-203 ENST00000563307.1: mRNA 4978 bp, protein 152 aa
CSNK2A2-204 ENST00000565188.1: mRNA 547 bp, protein 135 aa
CSNK2A2-205 ENST00000566813.5: mRNA 1569 bp, No protein
CSNK2A2-206 ENST00000567730.6: mRNA 947 bp, protein 230 aa (www.ensembl.org).

A related transcribed pseudogene is found on chromosome 11.

CK2 (casein kinase 2) is an evolutionarily protected protein kinase, and the deletion of both of its catalytic subunits is lethal. (Padmanabha et al., 1990).
The crystal structure of a fully active form (Tetramer) of human CK2 consisting of two C-terminally truncated (Alpha) catalytic and two regulatory (Beta) subunits (Protein Data Bank code: 1JWH). This protein is composed of 350 amino acids, with Molecular mass of 41213 Da. For two α subunits, α being 42 kDa and α being 38 kDa, and two β subunits, each weighing in at 28 kDa. The β subunits form homodimers which are building blocks to generate heterotetramers with the catalytic subunits (α or α) in which these two catalytic subunits in the holoenzyme make no contacts with each other (Niefind, Guerra et al. 2001). CK2 proteins can function as monomeric kinases or within a tetrameric complex of two CK2 kinase units and two units of the regulatory protein CK2b. ((Ortega, Seidner et al. 2014).
Quaternary structure is generally characterized by tight regulation. The enzyme acts independently of classical activating second messengers. (Ackermann, Neidhart et al. 2005). Unlike most other proteins, CK2 shows the rare ability dual-co-substrate specificity to use either ATP or GTP as phosphoryl donor. (Niefind et al., 1999).
CSNK2A2 encodes alpha prime polypeptide (the catalytic subunit of the protein kinase enzyme). The α subunits do not require the β regulatory subunits to function, this allows dimers to form of the catalytic domains independent of β subunit transcription. Catalytic subunit of kinase complex phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine such as casein (Pinna 2002). In mouse transgenic models CK2α is an oncogene and CK2α overexpression in mammary gland and lymphoid compartment leads to tumor formation (Seldin 1995).
CSNK2A2 protein also has interactions with other proteins such as CSNK2B, CSNK2A1, ENSG00000263020, JUN , TP53, SUPT16H, SSRP1, DVL3, DVL1, NFKBIA. https://www.sinobiological.com/resource/ck2-alpha-csnk2a1/proteins

In human, CSNK2A2 has a broad expression in testis (RPKM 55.0) and skin (RPKM 19.3) but also it is expressed in 24 other tissues including bone marrow, whole blood, lymph node, thymus, cerebellum, brain, retina, spinal cord, heart, smooth muscle, skeletal muscle, small intestine, colon, adipocyte, kidney, liver, lung, pancreas, thyroid, salivary gland, adrenal gland, ovary, uterus, placenta, cervix and prostate (Ortega, Seidner et al. 2014). https://www.genecards.org/cgi-bin/carddisp.pl?gene=CSNK2A2#expression.
A significant increase in expression of eight Wnt signaling pathway proteins including CSNK2A2, was detected in glioblastoma multiforme (GBM) (Shevchenko, Arnotskaya et al. 2020).
Experimental studies suggest that irregular expression of the alpha CK2 subunit transmits a oncogenic potential in the cells such that in cooperation with certain oncogenes it causes a profound increase in tumor phenotype. (Tawfic, Yu et al. 2001).
In addition, increased CSNK2A2 expression has been observed in breast cancer tissue and breast cancer cell lines, colon cancer progression as well as villous colon adenomas (Romieu-Mourez, Landesman-Bollag et al. 2001, Nibbe, Markowitz et al. 2009, Nguyen, Albers et al. 2010, Wang, Chang et al. 2016). Moreover, data on transcript expression of the specified gene (CK2) in cancer versus normal tissue revealed widespread upregulation in the expression of CK2 genes in primary tumor tissues (Ortega, Seidner et al. 2014).

CSNK2A2 is localized in the nucleus and cytosol. Nuclear matrix and chromatin described to be the key sites for signaling of the CK2 activity in relation to cell growth (Tawfic, Yu et al. 2001).

CSNK2A2 is responsible for phosphorylation of substrates containing acidic residues in various pathways within a cell; ATP or GTP can be used as phosphate source. Indeed, it can regulate numerous cellular processes, such as cell cycle progression, apoptosis, and transcription, as well as viral infection.
During mitosis CK2s anti-apoptotic function is in the continuation of the cell cycle; from G1 to S phase and G2 to M phase checkpoints, it functions as a component of the TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B- CDK1 activity and G2 arrest in response to spindle damage.
Comparison the induced expression of catalytically inactive CK2a in human osteosarcoma U2-OS cells suggested that CK2α may have unique functions associated with the control of proliferation or viability.
CSNK2A2 is also required for TP53-mediated apoptosis, phosphorylating Ser-392 of TP53 following UV irradiation.
CSNK2A2 also regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates HSP90AA1 (Hsp90) and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function.
It acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV (Keller, Zeng et al. 2001, Sayed, Pelech et al. 2001, Shin, Lee et al. 2005).
The Wnt pathway connection:
CSNK2A2 acts as a multi-site regulator of the Wnt pathway, and it is well known for phosphorylating CTNNB1 (β-catenin ) and the transcription factor LEF1.
Wnt signaling is initiated by binding of the secreted Wnt ligand to the members of the Frizzled receptor family. The level of β-catenin in the cytosol, is a key element in the Wnt pathway which triggers the activation of Wnt responsive genes. In the absence of Wnt stimulation, β-catenin is degraded by the proteasome (which depends upon β-catenin phosphorylation in a multi-protein complex by a hierarchical mechanism involving both CSNK1A1 (CK1) and GSK3). This phosphorylation is crucial for binding of β-catenin to the F-box protein βTrCP, which imparts specficity on the ubiquitination apparatus.
Wnt signaling inhibits GSK3 and prevents the ubiquitination and degradation of β-catenin, which leads to the accumulation of β-catenin in the cytosol and the activation of Wnt responsive genes, some of which are proto-oncogenes.
It is hypothesized that CK2 has dual role in the Wnt signaling pathway. First it can directly phosphorylate β-catenin and prevents its degradation by counteracting the effect of GSK3 phosphorylation within the negative regulatory complex (Son et al., 2000). Inhibition of CK2 decreases β-catenin level and blocks proliferation of Wnt-transfected cells. Suggesting that β-catenin phosphorylated by CK2 escapes ubiquitination and degradation, leading to an increased level of β-catenin available to activate Wnt-responsive genes.
On the other hand, CK2, by phosphorylating CDC34 (the E2 ubiquitin-conjugating enzyme UBC3), promotes its binding to the proteasome receptor β-TrCP, ultimately assisting the degradation of β-catenin (Semplici et al., 2002).
The apoptosis pathway connection:
Under survival conditions, CK2 phosphorylates proteins such as ARC and BID. When ARC is phosphorylated, it is targeted to mitochondria, where it inhibits CASP8 (caspase 8). Bid is resistant to cleavage by caspase 8, when it is phosphorylated by CK2. Under apoptotic conditions, CK2 phosphorylation sites on proteins such as BID and ARC are not phosphorylated, indeed ARC is not targeted to mitochondria and does not inhibit caspase 8. In the absence of phosphorylation, Bid is susceptible to cleavage by caspase 8.
The subsequent translocation of BID to the mitochondria is followed by release of cytochrome C that leads to the amplification of caspase activation (proteins, including MAX and HS1, become susceptible to caspase-mediated cleavage when they are not phosphorylated by CK2) (Litchfield 2003).
CSNK2A2 can also negatively regulate apoptosis by phosphorylating the caspases ( CASP9 and CASP2) and the apoptotic regulator NOL3. This phosphorylation, protects CASP9 from cleavage and activation by CASP8, so can inhibits the CASP2 dimerization and CASP8 activation.

The CSNK2A2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, S.cerevisiae, K.lactis, E.gossypii, A.thaliana, and rice.

First human condition associated with germline mutations in any of the CK2 subunits has been described by Volkan Okur (Volkan Okur, 2016 Jul) with a clinical phenotype of neurodevelopmental disabilities and dysmorphic features. Patients from five independent families with overlapping neurodevelopmental disorders and dysmorphic features were found to have likely damaging de novo splice site or missense variants in highly conserved regions of CSNK2A1. They found one splice site variant (c.824 + 2T>C) and four missense variants (p.R47Q, p.Y50S, p.D175G, p.K198R) in this gene.

Somatic mutations in CSNK2A1 have been implicated in various cancers by regulating downstream cancer-associated genes such as JAK/STAT, NF-kB, PI3K/AKT (Zheng et al. 2013).