CSNK1G1

protein-coding

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

Gene summary

This gene encodes a member of the casein kinase I gene family. This family is comprised of serine/threonine kinases that phosphorylate acidic proteins such as caseins. The encoded kinase plays a role in cell cycle checkpoint arrest in response to stalled replication forks by phosphorylating Claspin. A mutation in this gene may be associated with non-syndromic early-onset epilepsy (NSEOE). [provided by RefSeq, Jul 2016]

MANE transcript

NM_022048.5

Inheritance

ClinVar variants

P:1U:57B:7

Top phenotype

Neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr15:64,165,525-64,356,173

External References & Databases

Ensembl (ENSG00000169118)

Transcript & Mutation Effects

hg38 • Region Span ~190.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CSNK1G1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 42

not providedTotal: 16

Neurodevelopmental disorderTotal: 1

CSNK1G1-related developmental disorder with autism spectrum disorderTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022048.5. 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			2 clinvar	4 clinvar		6
missense			49 clinvar	3 clinvar		52
nonsense			1 clinvar			1
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	1	57	7	0	65

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022048.5	RefSeq	NP_071331.2	11	MANE Select
ENST00000303052.13	Ensembl	ENSP00000305777.7	11	MANE Select
NM_001329605.2	RefSeq	NP_001316534.1	12	Standard
NM_001329606.2	RefSeq	NP_001316535.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Hedgehog signaling pathway - Homo sapiens (human)
WNT-Core
Wnt Signaling Pathway
Hedgehog Signaling Pathway
IL-7 signaling

Biological Process

endocytosis
Wnt signaling pathway
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
positive regulation of canonical Wnt signaling pathway

Molecular Function

protein serine/threonine kinase activity
protein binding
ATP binding

Cellular Component

nucleus
cytoplasm
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000303052
Coding exons: 11
Length: 190727
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125744
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.99	151	237	0.636	0.0000127	2756
Missense (PolyPhen)		58	111.26	0.52128		1281
Synonymous	0.224	80	82.6	0.969	0.00000437	787
Loss of Function	4.66	2	29.1	0.0686	0.00000197	300

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine/threonine-protein kinase. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Regulates fast synaptic transmission mediated by glutamate (By similarity). Phosphorylates CLSPN. {ECO:0000250, ECO:0000269|PubMed:21680713}.;

Recessive Scores

pRec: 0.145

Intolerance Scores

LoFtool: 0.457
RVIS EVS: -0.34
RVIS percentile EVS: 30.37

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.938

Gene Damage Prediction

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