Hydrops fetalis: genes and variants

Genes linked to Hydrops fetalis

• FOXP3: Forkhead box protein P3

  It establishes the transcriptional program of regulatory T cells and is essential for maintaining peripheral immune tolerance. Loss-of-function variants cause IPEX syndrome with severe early-onset autoimmunity, enteropathy, eczema, and endocrine disease.

  1 disease-causing and 0 uncertain variants in FOXP3 are linked to Hydrops fetalis.

• 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.

  1 disease-causing and 0 uncertain variants in L1CAM are linked to Hydrops fetalis.

• RYR3: Ryanodine receptor 3

  An intracellular calcium-release channel that opens in response to calcium and releases more calcium from the endoplasmic or sarcoplasmic reticulum. This calcium-induced calcium release contributes to muscle contraction and broader calcium signaling in non-muscle cells.

  1 disease-causing and 0 uncertain variants in RYR3 are linked to Hydrops fetalis.

• PIEZO1: Piezo-type mechanosensitive ion channel component 1

  The protein forms a mechanically activated, nonselective cation channel that converts membrane tension into an electrical and calcium signal. It contributes to touch, blood-cell volume control, and lymphatic development, and PIEZO1 variants are associated with dehydrated stomatocytosis and lymphatic malformations.

  0 disease-causing and 5 uncertain variants in PIEZO1 are linked to Hydrops fetalis.

Known disease-causing variants in Hydrops fetalis

Same protein, different disease

• Insulin-dependent diabetes mellitus secretory diarrhea syndrome is also caused by FOXP3 variants; they fall mostly in different places as the Hydrops fetalis variants (16 disease-causing).
• X-linked hydrocephalus syndrome is also caused by L1CAM variants; they fall mostly in different places as the Hydrops fetalis variants (8 disease-causing).
• L1 syndrome is also caused by L1CAM variants; they fall mostly in different places as the Hydrops fetalis variants (7 disease-causing).
• MASA syndrome is also caused by L1CAM variants; they fall mostly in different places as the Hydrops fetalis variants (6 disease-causing).

Diseases related to Hydrops fetalis

• Insulin-dependent diabetes mellitus secretory diarrhea syndrome, also linked to FOXP3
• Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, also linked to PIEZO1
• Type 1 diabetes mellitus, also linked to FOXP3
• 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
• Lymphatic malformation, also linked to PIEZO1
• MASA syndrome, also linked to L1CAM
• Myopathy, also linked to RYR3
• Non-immune hydrops fetalis, also linked to PIEZO1
• X-linked complicated corpus callosum dysgenesis, also linked to L1CAM

Frequently asked questions

Which genes are linked to Hydrops fetalis?

In CATVariant, Hydrops fetalis is linked to 4 analyzed proteins: FOXP3 (Forkhead box protein P3), L1CAM (Neural cell adhesion molecule L1), RYR3 (Ryanodine receptor 3) and PIEZO1 (Piezo-type mechanosensitive ion channel component 1).

How many genetic variants are linked to Hydrops fetalis?

8 variants: 3 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 5 are of uncertain significance or have conflicting reports.

Which uncertain variants in Hydrops fetalis 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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