1. Panels
  2. Intellectual disability
  3. CSNK1G1
Genes in panel
Prev Next
Regions in panel
Prev Next

Intellectual disability

Gene: CSNK1G1

Green List (high evidence)
CSNK1G1 (casein kinase 1 gamma 1)
EnsemblGeneIds (GRCh38): ENSG00000169118
EnsemblGeneIds (GRCh37): ENSG00000169118
OMIM: 606274, Gene2Phenotype
CSNK1G1 is in 4 panels

6 reviews

Sarah Leigh (Genomics England Curator)

The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 9 Mar 2022, 3:40 p.m. | Last Modified: 9 Mar 2022, 3:40 p.m.
Panel Version: 3.1510
Created: 9 Mar 2022, 3:40 p.m.
Last Modified: 9 Mar 2022, 3:40 p.m.
Panel version: 3.1510

Arina Puzriakova (Genomics England Curator)

Comment on list classification: Upgraded from Red to Amber as now at least 5 unrelated individuals reported (PMID: 33009664). All present developmental delay of varying severity, although a formal ID assessment was not performed. Tagged 'for-review' to evaluate relevance of the phenotypes to this panel.
Created: 21 Dec 2020, 2:10 p.m. | Last Modified: 21 Dec 2020, 2:10 p.m.
Panel Version: 3.666
Created: 21 Dec 2020, 2:10 p.m.
Last Modified: 21 Dec 2020, 2:10 p.m.
Panel version: 3.666

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 presenting 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.
Created: 17 Oct 2020, 11:41 p.m. | Last Modified: 17 Oct 2020, 11:41 p.m.
Panel Version: 3.456

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

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

Publications

Created: 17 Oct 2020, 11:41 p.m.
Last Modified: 17 Oct 2020, 11:41 p.m.
Panel version: 3.456

Caroline Wright (Sanger)

Red List (low evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
EARLY INFANTILE EPILEPTIC ENCEPHALOPATHY AND MICROCEPHALY

Publications

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

Ellen McDonagh (Genomics England Curator)

Red List (low evidence)

One patient reported with severe non-syndromic early-onset epilepsy.
Created: 27 Oct 2017, 2:46 p.m.

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

Phenotypes
severe non-syndromic early-onset epilepsy

Publications

Created: 27 Oct 2017, 2:46 p.m.

Panel version: Imported from Intellectual disability update Oct 2017 panel version 0.2

Lu Raymond (university of cambridge )

Red List (low evidence)

Created: 23 Feb 2016, 11:10 a.m.

Panel version: 0.306

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
Phenotypes
  • severe non-syndromic early-onset epilepsy
  • Global developmental delay
  • Intellectual disability
  • Autism
  • Seizures
  • Abnormality of the face
  • Abnormality of limbs
Tags
gene-checked
OMIM
606274
Clinvar variants
Variants in CSNK1G1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

3 May 2022, Gel status: 3

Added Tag

Sarah Leigh (Genomics England Curator)

Tag gene-checked tag was added to gene: CSNK1G1.

10 Mar 2022, Gel status: 3

Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review was removed from gene: CSNK1G1.

9 Mar 2022, Gel status: 3

Added New Source, Status Update

Arina Puzriakova (Genomics England Curator)

Source Expert Review Green was added to CSNK1G1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)

21 Dec 2020, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: csnk1g1 has been classified as Amber List (Moderate Evidence).

21 Dec 2020, Gel status: 1

Added Tag

Arina Puzriakova (Genomics England Curator)

Tag for-review tag was added to gene: CSNK1G1.

14 Dec 2020, Gel status: 1

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: CSNK1G1 were changed from severe non-syndromic early-onset epilepsy to severe non-syndromic early-onset epilepsy; Global developmental delay; Intellectual disability; Autism; Seizures; Abnormality of the face; Abnormality of limbs

14 Dec 2020, Gel status: 1

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: CSNK1G1 were set to 24463883

12 Mar 2018, Gel status: 1

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

29 Nov 2017, Gel status: 1

Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Model of inheritance for gene CSNK1G1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Nov 2015, Gel status: 1

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

CSNK1G1 was added to Intellectual disabilitypanel. Sources: Expert Review Red

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

CSNK1G1 was created by ellenmcdonagh