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Intellectual disability syndromic and non-syndromic

Gene: CSNK1G1

Green List (high evidence)

CSNK1G1 (casein kinase 1 gamma 1)
EnsemblGeneIds (GRCh38): ENSG00000169118
EnsemblGeneIds (GRCh37): ENSG00000169118
OMIM: 606274, Gene2Phenotype
CSNK1G1 is in 2 panels

3 reviews

Rylee Peters (Victorian Clinical Genetics Services)

I don't know

Gold et al 2020 (PMID: 33009664): 4/5 of the reported CSNK1G1 variants in this paper are present in the population (gnomAD v4). The two missense variants have 4 hets and 7 hets in v4, splice variant has 7 hets in v4, nonsense variant (predicted to escape NMD) has 1 het in v4, the exonic deletion (NMD-predicted) is absent in v4.
Created: 13 Aug 2024, 2:05 a.m. | Last Modified: 13 Aug 2024, 2:05 a.m.
Panel Version: 0.6122

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurodevelopmental disorder, MONDO:0700092, CSNK1G-related

Publications

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Comment when marking as ready: Borderline Green/Amber rating.
Created: 18 Oct 2020, 2:19 a.m. | Last Modified: 18 Oct 2020, 2:19 a.m.
Panel Version: 0.3081

Konstantinos Varvagiannis (Other)

I don't know

Gold et al (2020 - PMID: 33009664) report 5 individuals with CSNK1G1 variants, including updated information on a previously reported subject (Martin et al 2014 - PMID: 24463883).

Features included DD (5/5) with associated expressive language delay, ASD (in at least 3/5), seizures (2/5), dysmorphic facial features (4/5 arched eyebrows, 3/5 prominent central incisors, 2/5 epicanthus) and limb anomalies (2/5 - proximally placed thumb, 5th f. clinodactyly, asymmetric overgrowth - the other individual had tapering fingers). GI problems were observed in 4/5. Two individuals had macrocephaly and one had microcephaly. There was no formal developmental assessment although ID might be implied in at least 3 individuals (p1: 20y - single words/regression in walking following a seizure episode, p2: 8y - first words at 5y, assistance to feed, dress and bathe, ASD, p4: 13y - regression, assistance to feed and dress).

CSNK1G1 encodes the gamma-1 isoform of casein kinase 1, a protein involved in growth and cell morphogenesis. The gene has ubiquitous expression, incl. brain. As commented, in brain it regulates phosphorylation of NMDA receptors, playing a role in synaptic transmission (4 articles cited).

One individual had a 1.2 kb deletion spanning exon 3 of CSNK1G1 [chr15:64550952-64552120 - GRCh37]. Parental samples were unavailable for this individual. Four individuals were found to harbor de novo CSNK1G1 variants [NM_022048.3: c.688C>T - p.(Arg230Trp) dn | c.1255C>T - p.(Gln419*) dn | c.1214+5G>A dn with in silico predictions in favor of splice disruption | c.419C>T - p.(Thr140Met) dn].

Arg230Trp is however present once in gnomAD. The stopgain variant is located in the last exon and predicted to skip NMD.

There were no variant studies performed.

The Drosophila gish gene encodes a CK1γ homolog with preferential expression in the mushroom body. Heterozygous and homozygous mutants exhibit impairment in memory retention, more severe in homozygous flies. gish was also identified as a seizure modifier in a fly epilepsy model (heterozygous para mt flies).

The authors also speculate that impaired transduction of LRP6 (and WNT signaling) might be implicated.

Finally the authors discuss the phenotype of individuals in Decipher one of whom (327861) harbors a frameshift variant and presented ID, epilepsy and progressive spasticity. [NB. Inheritance of this variant is not specified, while this individual has a further inherited SCN2A missense SNV]. Two further Decipher cases with microdeletions spanning CSNK1G1 (and additional variants) are also discussed.

Overall, this gene can be considered for inclusion with probably amber rating.
Sources: Literature
Created: 17 Oct 2020, 11:39 p.m. | Last Modified: 17 Oct 2020, 11:43 p.m.
Panel Version: 0.3078

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of the face; Abnromality of limbs

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
Phenotypes
  • Neurodevelopmental disorder, MONDO:0700092, CSNK1G-related
OMIM
606274
Clinvar variants
Variants in CSNK1G1
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

2 Oct 2023, Gel status: 3

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: CSNK1G1 were changed from Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of the face; Abnromality of limbs to Neurodevelopmental disorder, MONDO:0700092, CSNK1G-related

18 Oct 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: csnk1g1 has been classified as Green List (High Evidence).

18 Oct 2020, Gel status: 3

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: csnk1g1 has been classified as Green List (High Evidence).

17 Oct 2020, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: CSNK1G1 was added gene: CSNK1G1 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature Mode of inheritance for gene: CSNK1G1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: CSNK1G1 were set to 33009664 Phenotypes for gene: CSNK1G1 were set to Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of the face; Abnromality of limbs Penetrance for gene: CSNK1G1 were set to unknown Review for gene: CSNK1G1 was set to AMBER