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  3. C12orf66
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Early onset or syndromic epilepsy

Gene: C12orf66

Amber List (moderate evidence)
C12orf66 (chromosome 12 open reading frame 66)
EnsemblGeneIds (GRCh38): ENSG00000174206
EnsemblGeneIds (GRCh37): ENSG00000174206
OMIM: 617420, Gene2Phenotype
C12orf66 is in 3 panels

2 reviews

John Taylor (Oxford Medical Genetics Laboratory)

Green List (high evidence)

Buchert et al., 2025 detailed 8 families with autosomal recessive variants in the KICS2 gene (previously known as C12orf66). Some of these families had two affected sibs with some phenotypic variability (e.g. seizures or not and no speech vs babbling).

In vitro assays suggest a dysregulation of mTORC1 activity and zebrafish models suggest an impact on embryonic development.

No individuals with a homozygous LOF variant in gnomADv4.1.0.
Created: 14 Jan 2026, 10:29 a.m. | Last Modified: 14 Jan 2026, 10:29 a.m.
Panel Version: 8.93

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Seizure; Intellectual disability; delayed speech.

Publications

Created: 14 Jan 2026, 10:29 a.m.
Last Modified: 14 Jan 2026, 10:29 a.m.
Panel version: 8.93

Arina Puzriakova (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green the next GMS panel update.
Created: 17 Mar 2025, 4:11 p.m. | Last Modified: 17 Mar 2025, 4:11 p.m.
Panel Version: 7.64
Added new-gene-name tag, new approved HGNC gene symbol for C12orf66 is KICS2
Created: 17 Mar 2025, 4:09 p.m. | Last Modified: 17 Mar 2025, 4:09 p.m.
Panel Version: 7.63
PMID: 39824192 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Created: 17 Mar 2025, 4:07 p.m. | Last Modified: 17 Mar 2025, 4:07 p.m.
Panel Version: 7.63
This gene is associated with a relevant phenotype in OMIM (MIM# 621100)

- PMID: 39824192 (2025) - biallelic variants in KICS2 in 11 individuals from 8 families with intellectual disability. All affected individuals had mild to severe intellectual disability, with 8 individuals also presenting with seizures and 3 (2 families) with hearing impairment. Functional studies in cell culture and zebrafish models provided evidence of pathogenicity, showing impaired mTORC1 regulation and effects on ciliogenesis.
Sources: Literature
Created: 17 Mar 2025, 4 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual developmental disorder, autosomal recessive 83, OMIM:621100

Publications

Created: 17 Mar 2025, 4 p.m.

Panel version: 7.63

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Intellectual developmental disorder, autosomal recessive 83, OMIM:621100
Tags
new-gene-name Q1_25_ promote_green
OMIM
617420
Clinvar variants
Variants in C12orf66
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Mar 2025, Gel status: 2

Entity classified by Genomics England curator

Arina Puzriakova (Genomics England Curator)

Gene: c12orf66 has been classified as Amber List (Moderate Evidence).

17 Mar 2025, Gel status: 1

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

Arina Puzriakova (Genomics England Curator)

gene: C12orf66 was added gene: C12orf66 was added to Early onset or syndromic epilepsy. Sources: Literature new-gene-name, Q1_25_ promote_green tags were added to gene: C12orf66. Mode of inheritance for gene: C12orf66 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: C12orf66 were set to 39824192 Phenotypes for gene: C12orf66 were set to Intellectual developmental disorder, autosomal recessive 83, OMIM:621100 Review for gene: C12orf66 was set to GREEN