MASA syndrome: genes and variants
MASA syndrome is linked to 1 analyzed protein (L1CAM). 6 DNA variants are known to cause it; 18 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 MASA 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.
6 disease-causing and 18 uncertain variants in L1CAM are linked to MASA syndrome.
Where MASA syndrome variants cluster
- L1CAM Ig-like C2-type 2 (positions 139–226): 3 of 6 disease-causing changes, 7.1× more than its size predicts.
Known disease-causing variants in MASA syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| L1CAM R473C | 473 | Ig-like C2-type 5 | Disease-causing (★★) |
| L1CAM N408D | 408 | Ig-like C2-type 4 | Disease-causing (★) |
| L1CAM R217G | 217 | Ig-like C2-type 2 | Disease-causing (★) |
| L1CAM I179S | 179 | Ig-like C2-type 2 | Disease-causing |
| L1CAM H210Q | 210 | Ig-like C2-type 2 | Disease-causing |
| L1CAM D598N | 598 | Ig-like C2-type 6 | Disease-causing |
Same protein, different disease
- X-linked hydrocephalus syndrome is also caused by L1CAM variants; they fall mostly in different places as the MASA syndrome variants (8 disease-causing).
- L1 syndrome is also caused by L1CAM variants; they fall mostly in different places as the MASA syndrome variants (7 disease-causing).
Diseases related to MASA syndrome
- X-linked hydrocephalus syndrome, also linked to L1CAM
- L1 syndrome, also linked to L1CAM
- Muscular dystrophy, limb-girdle, autosomal recessive 23, 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 MASA syndrome?
In CATVariant, MASA syndrome is linked to 1 analyzed protein: L1CAM (Neural cell adhesion molecule L1).
How many genetic variants are linked to MASA syndrome?
38 variants: 6 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 18 are of uncertain significance or have conflicting reports.
Which uncertain variants in MASA 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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