CSNK2A1

casein kinase 2 alpha 1

Basic information

Region (hg38): 20:472498-543835

Links

ENSG00000101266 ∙ NCBI:1457 ∙ OMIM:115440 ∙ HGNC:2457 ∙ Uniprot:P68400 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Okur-Chung neurodevelopmental syndrome (Strong), mode of inheritance: AD
• Okur-Chung neurodevelopmental syndrome (Strong), mode of inheritance: AD
• Okur-Chung neurodevelopmental syndrome (Moderate), mode of inheritance: AD
• Okur-Chung neurodevelopmental syndrome (Definitive), mode of inheritance: AD
• syndromic intellectual disability (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Okur-Chung neurodevelopmental syndrome	AD	Allergy/Immunology/Infectious	Among other findings, individuals have been described with hypogammaglobulinemia and mild IgA or IgG deficiency and awareness may allow surveillance and management related to potential infectious sequelae	Allergy/Immunology/Infectious; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic	27048600; 28725024; 29240241; 29383814; 29619237

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CSNK2A1 gene.

• not provided (13 variants)
• Okur-Chung neurodevelopmental syndrome (8 variants)
• Inborn genetic diseases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CSNK2A1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	2	7
missense	7	15	32	5		59
nonsense	5	5	2			12
start loss	1					1
frameshift	2	3	2			7
inframe indel			2			2
splice donor/acceptor (+/-2bp)	3	2				5
splice region			3	3		6
non coding	1	3	3	27	23	57
Total	19	28	41	37	25

Highest pathogenic variant AF is 0.00000659

Variants in CSNK2A1

This is a list of pathogenic ClinVar variants found in the CSNK2A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
20-478662-C-G			Likely benign (Jul 01, 2024)
20-478699-C-G			Likely benign (Nov 01, 2021)
20-478765-C-CAAAA			Likely benign (Apr 01, 2024)
20-483804-AT-A			Benign (Jul 03, 2018)
20-483959-C-T		CSNK2A1-related disorder	Benign (Apr 08, 2019)
20-483960-G-A			Benign/Likely benign (Nov 01, 2023)
20-483965-T-C			Likely benign (Jun 27, 2022)
20-483972-C-T		Inborn genetic diseases	Likely benign (Oct 06, 2022)
20-483978-C-T		Inborn genetic diseases	Benign/Likely benign (Aug 08, 2022)
20-483992-G-A		Okur-Chung neurodevelopmental syndrome	Uncertain significance (Aug 22, 2019)
20-484033-T-C			Benign (Jan 03, 2019)
20-484049-G-T		Okur-Chung neurodevelopmental syndrome	Uncertain significance (Oct 03, 2019)
20-484050-G-A		Inborn genetic diseases	Likely benign (Oct 25, 2023)
20-484053-A-C			Likely benign (Dec 26, 2019)
20-484055-G-T		Inborn genetic diseases	Uncertain significance (Dec 04, 2023)
20-484071-A-T		Okur-Chung neurodevelopmental syndrome	Uncertain significance (Aug 15, 2022)
20-484085-A-G		Okur-Chung neurodevelopmental syndrome	Benign/Likely benign (Aug 01, 2023)
20-484151-G-A			Likely benign (Oct 09, 2018)
20-484233-T-C			Likely benign (Apr 24, 2019)
20-486400-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jun 10, 2024)
20-486410-G-GC			Likely pathogenic (May 11, 2023)
20-486411-C-T		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
20-486423-C-G		Okur-Chung neurodevelopmental syndrome	Uncertain significance (-)
20-486423-C-T		Inborn genetic diseases	Likely benign (May 12, 2024)
20-486433-C-T			Uncertain significance (May 24, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CSNK2A1	protein_coding	protein_coding	ENST00000217244	12	65350

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.987	0.0129	125738	0	6	125744	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.71	66	221	0.298	0.0000118	2554
Missense in Polyphen		11	96.258	0.11428		1140
Synonymous	0.343	75	78.9	0.951	0.00000443	716
Loss of Function	4.47	4	30.8	0.130	0.00000214	302

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000120	0.000120
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000884	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8. 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 Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. 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. Phosphorylates PML at 'Ser-565' and primes it for ubiquitin- mediated degradation. Plays an important role in the circadian clock function by phosphorylating ARNTL/BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry (PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:19188443, PubMed:20625391, PubMed:22406621). Phosphorylates CCAR2 at 'Thr-454' in gastric carcinoma tissue (PubMed:24962073). {ECO:0000269|PubMed:11239457, ECO:0000269|PubMed:11704824, ECO:0000269|PubMed:16193064, ECO:0000269|PubMed:19188443, ECO:0000269|PubMed:20625391, ECO:0000269|PubMed:22406621, ECO:0000269|PubMed:24962073}.
• Disease: DISEASE: Okur-Chung neurodevelopmental syndrome (OCNDS) [MIM:617062]: An autosomal dominant neurodevelopmental disorder characterized by developmental delay, intellectual disability, behavioral problems, hypotonia, speech problems, microcephaly, pachygyria and variable dysmorphic features. {ECO:0000269|PubMed:27048600}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Adherens junction - Homo sapiens (human);Ribosome biogenesis in eukaryotes - Homo sapiens (human);Mitophagy - animal - Homo sapiens (human);Measles - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Epstein-Barr virus infection - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);TNF alpha Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;nerve growth factor pathway (ngf);Wnt Signaling Pathway;Developmental Biology;Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding;Signaling by WNT;Signal Transduction;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;wnt signaling pathway;lissencephaly gene (lis1) in neuronal migration and development;segmentation clock;multi-step regulation of transcription by pitx2;bcr signaling pathway;calcium signaling by hbx of hepatitis b virus;Generic Transcription Pathway;Regulation of PTEN stability and activity;Metabolism of lipids;Metabolism of proteins;igf-1 signaling pathway;RNA Polymerase II Transcription;Chaperonin-mediated protein folding;Metabolism;Fibroblast growth factor-1;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;Synthesis of PC;Receptor Mediated Mitophagy;Mitophagy;pdgf signaling pathway;tpo signaling pathway;BCR signaling pathway;PTEN Regulation;PIP3 activates AKT signaling;Protein folding;Regulation of TP53 Activity through Phosphorylation;Condensation of Prometaphase Chromosomes;Signal transduction by L1;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Mitotic Prometaphase;L1CAM interactions;Glycerophospholipid biosynthesis;Phospholipid metabolism;Axon guidance;M Phase;Cell Cycle;TNFalpha;Cell Cycle, Mitotic;Intracellular signaling by second messengers;WNT mediated activation of DVL;Transcriptional regulation by RUNX1;TCF dependent signaling in response to WNT;Alpha-synuclein signaling;Role of Calcineurin-dependent NFAT signaling in lymphocytes;Lissencephaly gene (LIS1) in neuronal migration and development;Presenilin action in Notch and Wnt signaling;PDGFR-alpha signaling pathway (Consensus)

Recessive Scores

• pRec: 0.796

Intolerance Scores

• loftool: 0.182
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.998
• hipred: Y
• hipred_score: 0.724
• ghis: 0.706

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.877

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Csnk2a1
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype; embryo phenotype

Gene ontology

• Biological process: protein phosphorylation;apoptotic process;cell cycle;signal transduction;positive regulation of cell population proliferation;Wnt signaling pathway;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;positive regulation of Wnt signaling pathway;positive regulation of cell growth;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;positive regulation of protein catabolic process;rhythmic process;chaperone-mediated protein folding;regulation of signal transduction by p53 class mediator;regulation of chromosome separation;negative regulation of ubiquitin-dependent protein catabolic process;negative regulation of apoptotic signaling pathway
• Cellular component: nucleus;nucleoplasm;cytosol;plasma membrane;protein kinase CK2 complex;Sin3 complex;NuRD complex;PcG protein complex
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;kinase activity;identical protein binding;protein N-terminus binding;Hsp90 protein binding