Early onset or syndromic epilepsy

Gene: C12orf66

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 11 Mar 2026, 3:39 p.m. | Last Modified: 11 Mar 2026, 3:39 p.m.

Panel Version: 8.134

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

• 39824192

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

• 39824192