L1 syndrome: genes and variants
L1 syndrome is linked to 1 analyzed protein (L1CAM). 7 DNA variants are known to cause it; 0 more are uncertain, and 0 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to L1 syndrome
L1CAM: Neural cell adhesion molecule L1
It promotes neuronal adhesion, axon guidance, neurite growth, and fasciculation during nervous-system development. Loss-of-function variants cause L1 syndrome, encompassing X-linked hydrocephalus, MASA syndrome, spastic paraplegia, and variable intellectual disability.
7 disease-causing and 0 uncertain variants in L1CAM are linked to L1 syndrome.
Known disease-causing variants in L1 syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| L1CAM P240L | 240 | Ig-like C2-type 3 | Disease-causing (★★) |
| L1CAM P333R | 333 | Ig-like C2-type 4 | Disease-causing (★★) |
| L1CAM G452R | 452 | Ig-like C2-type 5 | Disease-causing (★★) |
| L1CAM R473C | 473 | Ig-like C2-type 5 | Disease-causing (★★) |
| L1CAM V752M | 752 | Fibronectin type-III 2 | Disease-causing (★★) |
| L1CAM S1224L | 1224 | Cytoplasmic | Disease-causing (★★) |
| L1CAM R184Q | 184 | Ig-like C2-type 2 | Disease-causing (★★) |
Same protein, different disease
- X-linked hydrocephalus syndrome is also caused by L1CAM variants; they fall mostly in different places as the L1 syndrome variants (8 disease-causing).
- MASA syndrome is also caused by L1CAM variants; they fall mostly in different places as the L1 syndrome variants (6 disease-causing).
Diseases related to L1 syndrome
- X-linked hydrocephalus syndrome, also linked to L1CAM
- Muscular dystrophy, limb-girdle, autosomal recessive 23, also linked to L1CAM
- MASA syndrome, also linked to L1CAM
- Hydrops fetalis, also linked to L1CAM
- X-linked complicated corpus callosum dysgenesis, also linked to L1CAM
Frequently asked questions
Which genes are linked to L1 syndrome?
In CATVariant, L1 syndrome is linked to 1 analyzed protein: L1CAM (Neural cell adhesion molecule L1).
How many genetic variants are linked to L1 syndrome?
10 variants: 7 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 0 are of uncertain significance or have conflicting reports.
Which uncertain variants in L1 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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