CASK (O14936) variants and mutations

CASK (also known as O14936) is a human protein-coding gene encoding a peripheral plasma membrane protein. It organizes synaptic and cell-junction protein complexes and also participates in transcriptional regulation during brain development. Loss-of-function variants can cause microcephaly with pontine and cerebellar hypoplasia, intellectual disability, epilepsy, and other X-linked neurodevelopmental phenotypes. This analysis covers 954 CASK variants and mutations. Of these, 63% have computational variant effect predictions. Disease context includes X-linked intellectual disability, Najm type, syndromic X-linked intellectual disability Najm type, and FG syndrome 4. Example CASK variants include M1L, M1V, and A2D.

Variant analysis overview

Gene: CASK
Protein: O14936
UniProt accession: O14936
Organism: Homo sapiens
Variants analyzed: 954
Variant scope: all variants
Completed: 2026-08-19

Variant and mutation evidence

Variant composition: 778 unspecified-consequence records; 57 synonymous variants; 104 missense variants; 3 in-frame deletions; 5 stop-gained variants; 2 splice-region variants; 2 frameshift variants; 1 in-frame insertions; 2 substitution
Prediction scores: 604 variants have prediction scores (63% of the analyzed set).

Clinical, disease, and population context

Disease context: 25 disease associations are represented. Top associations: X-linked intellectual disability, Najm type, syndromic X-linked intellectual disability Najm type, FG syndrome 4, cask-related x-linked intellectual disability, FG syndrome, hereditary disease, Intellectual disability, pontocerebellar hypoplasia, X-linked non-syndromic intellectual disability, developmental disability, X-linked syndromic intellectual disability, neurodevelopmental disorder.

Protein structure and variant hotspots

Protein features: 6 domains; 2 binding sites; 8 post-translational modification sites.
Structural context: 752 variants have structural context.
PTM context: 9 variants overlap post-translational modification sites.
Experimental data: 82 protein positions have experimental scores. Source: CASK PDZ domain domainome 1.0.

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable CASK variants

Examples include M1L, M1V, A2D, A2T, D3N, D5E, D5N, D5Y. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.

CASK analysis run — CASK (954 variants) — completed 2026-08-19