Periventricular nodular heterotopia: genes and variants
Periventricular nodular heterotopia is linked to 2 analyzed proteins (NEDD4L and FLNA). 6 DNA variants are known to cause it; 49 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: periventricular nodular heterotopia 7
Genes linked to Periventricular nodular heterotopia
NEDD4L: E3 ubiquitin-protein ligase NEDD4-like
An E3 ubiquitin ligase that labels target proteins for trafficking, signaling, or degradation. It regulates pathways including autophagy and can control the surface abundance of ion channels, linking NEDD4L biology to neuronal excitability and disease.
5 disease-causing and 49 uncertain variants in NEDD4L are linked to Periventricular nodular heterotopia.
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.
1 disease-causing and 0 uncertain variants in FLNA are linked to Periventricular nodular heterotopia.
Where Periventricular nodular heterotopia variants cluster
- NEDD4L HECT (positions 640–974): 4 of 5 disease-causing changes, 2.3× more than its size predicts.
Known disease-causing variants in Periventricular nodular heterotopia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| NEDD4L R208Q | 208 | WW 1 | Disease-causing (★★) |
| NEDD4L M749V | 749 | HECT | Disease-causing (★★) |
| NEDD4L E893K | 893 | HECT | Disease-causing (★★) |
| FLNA D125N | 125 | Calponin-homology (CH) 1 | Disease-causing (★) |
| NEDD4L Y679C | 679 | HECT | Disease-causing |
| NEDD4L Q694H | 694 | HECT | Disease-causing |
Same protein, different disease
- Oto-palato-digital syndrome, type II is also caused by FLNA variants; they fall mostly in different places as the Periventricular nodular heterotopia variants (14 disease-causing).
- Heterotopia, periventricular, X-linked dominant is also caused by FLNA variants; they fall mostly in different places as the Periventricular nodular heterotopia variants (14 disease-causing).
- Frontometaphyseal dysplasia is also caused by FLNA variants; they fall mostly in different places as the Periventricular nodular heterotopia variants (12 disease-causing).
- Melnick-Needles syndrome is also caused by FLNA variants; they fall mostly in different places as the Periventricular nodular heterotopia variants (8 disease-causing).
- Cardiac valvular dysplasia, X-linked is also caused by FLNA variants; they fall mostly in different places as the Periventricular nodular heterotopia variants (4 disease-causing).
Diseases related to Periventricular nodular heterotopia
- 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
- FG syndrome, also linked to FLNA
- Cardiac valvular dysplasia, X-linked, also linked to FLNA
Frequently asked questions
Which genes are linked to Periventricular nodular heterotopia?
In CATVariant, Periventricular nodular heterotopia is linked to 2 analyzed proteins: NEDD4L (E3 ubiquitin-protein ligase NEDD4-like) and FLNA (Filamin-A).
How many genetic variants are linked to Periventricular nodular heterotopia?
67 variants: 6 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 49 are of uncertain significance or have conflicting reports.
Which uncertain variants in Periventricular nodular heterotopia 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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