CSNK1E

protein-coding

casein kinase 1 epsilon, the group of casein kinase 1 family

Gene summary

The protein encoded by this gene is a serine/threonine protein kinase and a member of the casein kinase I protein family, whose members have been implicated in the control of cytoplasmic and nuclear processes, including DNA replication and repair. The encoded protein is found in the cytoplasm as a monomer and can phosphorylate a variety of proteins, including itself. This protein has been shown to phosphorylate period, a circadian rhythm protein. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2014]

MANE transcript

NM_152221.3

Inheritance

ClinVar variants

P:1U:39B:1

Top phenotype

Moderate intellectual disability

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr22:38,290,691-38,318,084

External References & Databases

Ensembl (ENSG00000213923)

Transcript & Mutation Effects

hg38 • Region Span ~27.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

genetic developmental and epileptic encephalopathyLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100062

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CSNK1E variants in ClinVar

15 Conditions Cataloged

not specifiedTotal: 31

not providedTotal: 6

Moderate intellectual disabilityTotal: 1

Decreased response to growth hormone stimulation testTotal: 1

Cardiac arrhythmiaTotal: 1

Delayed speech and language developmentTotal: 1

Cerebellar ataxiaTotal: 1

BradycardiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152221.3. 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			1 clinvar		1 clinvar	2
missense			36 clinvar			36
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)	1 clinvar		2 clinvar			3
Total	1	0	39	0	1	41

Highest pathogenic variant AF is 6.841312e-7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 62 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152221.3	RefSeq	NP_689407.1	9	MANE Select
ENST00000396832.6	Ensembl	ENSP00000380044.1	9	MANE Select
NM_001894.5	RefSeq	NP_001885.1	9	Standard
ENST00000359867.7	Ensembl	ENSP00000352929.3	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Circadian rhythm - Homo sapiens (human)
FoxO signaling pathway - Homo sapiens (human)
Hippo signaling pathway - Homo sapiens (human)
Hippo signaling pathway - multiple species - Homo sapiens (human)
Wnt signaling pathway - Homo sapiens (human)

Biological Process

G2/M transition of mitotic cell cycle
DNA repair
protein phosphorylation
endocytosis
signal transduction

Molecular Function

RNA binding
protein kinase activity
protein serine/threonine kinase activity
protein binding
ATP binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000396832
Coding exons: 9
Length: 107831
Individuals with no LoFs: 125742
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 125745
p: 0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.18	136	288	0.472	0.0000209	2688
Missense (PolyPhen)		57	127.52	0.44698		1149
Synonymous	0.242	116	119	0.972	0.00000869	828
Loss of Function	4.23	0	20.8	0.00	0.00000112	224

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates DVL1 and DVL2. Central component of the circadian clock. In balance with PP1, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. Controls PER1 and PER2 nuclear transport and degradation. Inhibits cytokine-induced granuloytic differentiation. {ECO:0000269|PubMed:12556519, ECO:0000269|PubMed:15070676, ECO:0000269|PubMed:15917222, ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:23413191}.;

Recessive Scores

pRec: 0.586

Intolerance Scores

LoFtool: 0.348
RVIS EVS: -0.34
RVIS percentile EVS: 30.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.959

Gene Damage Prediction

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