FG syndrome: genes and variants
FG syndrome is linked to 2 analyzed proteins (CASK and FLNA). 4 DNA variants are known to cause it; 28 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: FG syndrome 2; FG syndrome 4
Genes linked to FG syndrome
CASK: Peripheral plasma membrane protein CASK
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.
4 disease-causing and 22 uncertain variants in CASK are linked to FG syndrome.
FLNA: Filamin-A
It crosslinks actin and connects the cytoskeleton to membrane receptors and signaling proteins during cell migration and tissue morphogenesis. Pathogenic variants cause a broad spectrum including periventricular nodular heterotopia and several skeletal or connective-tissue disorders.
0 disease-causing and 6 uncertain variants in FLNA are linked to FG syndrome.
Known disease-causing variants in FG syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CASK R489Q | 489 | PDZ | Disease-causing (★★) |
| CASK E102G | 102 | Protein kinase | Disease-causing (★★) |
| CASK V854A | 854 | Guanylate kinase-like | Disease-causing (★) |
| CASK S155L | 155 | Protein kinase | Disease-causing (★) |
Same protein, different disease
- Syndromic X-linked intellectual disability Najm type is also caused by CASK variants; they fall mostly in different places as the FG syndrome variants (8 disease-causing).
Diseases related to FG syndrome
- Familial thoracic aortic aneurysm and aortic dissection, also linked to FLNA
- Connective tissue disorder, also linked to FLNA
- Heterotopia, periventricular, X-linked dominant, also linked to FLNA
- Oto-palato-digital syndrome, type II, also linked to FLNA
- Frontometaphyseal dysplasia, also linked to FLNA
- Melnick-Needles syndrome, also linked to FLNA
- Syndromic X-linked intellectual disability Najm type, also linked to CASK
- Developmental disorder, also linked to CASK
- Periventricular nodular heterotopia, also linked to FLNA
- Cardiac valvular dysplasia, X-linked, also linked to FLNA
- Intellectual disability, CASK-related, X-linked, also linked to CASK
Frequently asked questions
Which genes are linked to FG syndrome?
In CATVariant, FG syndrome is linked to 2 analyzed proteins: CASK (Peripheral plasma membrane protein CASK) and FLNA (Filamin-A).
How many genetic variants are linked to FG syndrome?
43 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 28 are of uncertain significance or have conflicting reports.
Which uncertain variants in FG syndrome look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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