Non-immune hydrops fetalis: genes and variants

Genes linked to Non-immune 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.

  2 disease-causing and 2 uncertain variants in PIEZO1 are linked to Non-immune hydrops fetalis.

• HRAS: GTPase HRas

  Its GTP-bound state activates RAF-MEK-ERK and other pathways downstream of growth-factor receptors. Somatic activating variants drive several cancers, while germline activating variants cause Costello syndrome.

  1 disease-causing and 0 uncertain variants in HRAS are linked to Non-immune hydrops fetalis.

• PTPN11: Tyrosine-protein phosphatase non-receptor type 11

  Its SHP2 phosphatase activity promotes RAS-MAPK signaling downstream of many receptor tyrosine kinases and cytokine receptors. Germline dysregulating variants cause Noonan-spectrum disorders, while somatic activating variants drive juvenile myelomonocytic leukemia and other cancers.

  1 disease-causing and 0 uncertain variants in PTPN11 are linked to Non-immune hydrops fetalis.

Weakly linked (only a few uncertain records): RIT1, KRAS and NSD1.

Known disease-causing variants in Non-immune hydrops fetalis

Same protein, different disease

• Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema is also caused by PIEZO1 variants; they fall mostly in different places as the Non-immune hydrops fetalis variants (12 disease-causing).
• Lymphatic malformation is also caused by PIEZO1 variants; they fall mostly in different places as the Non-immune hydrops fetalis variants (6 disease-causing).
• Costello syndrome is also caused by HRAS variants; they fall mostly in different places as the Non-immune hydrops fetalis variants (15 disease-causing).
• RASopathy is also caused by HRAS variants; they fall mostly in different places as the Non-immune hydrops fetalis variants (6 disease-causing).
• Large congenital melanocytic nevus is also caused by HRAS variants; they fall partly in the same places as the Non-immune hydrops fetalis variants (5 disease-causing).
• Thyroid cancer, nonmedullary, 2 is also caused by HRAS variants; they fall partly in the same places as the Non-immune hydrops fetalis variants (3 disease-causing).
• RASopathy is also caused by PTPN11 variants; they fall mostly in different places as the Non-immune hydrops fetalis variants (51 disease-causing).
• Noonan syndrome is also caused by PTPN11 variants; they fall mostly in different places as the Non-immune hydrops fetalis variants (44 disease-causing).
• Noonan syndrome and Noonan-related syndrome is also caused by PTPN11 variants; they fall mostly in different places as the Non-immune hydrops fetalis variants (29 disease-causing).
• LEOPARD syndrome 1 is also caused by PTPN11 variants; they fall mostly in different places as the Non-immune hydrops fetalis variants (16 disease-causing).
• Metachondromatosis is also caused by PTPN11 variants; they fall mostly in different places as the Non-immune hydrops fetalis variants (11 disease-causing).

Diseases related to Non-immune hydrops fetalis

• RASopathy, also linked to HRAS and PTPN11
• Noonan syndrome, also linked to HRAS and PTPN11
• Noonan syndrome and Noonan-related syndrome, also linked to HRAS and PTPN11
• Hypertrophic cardiomyopathy, also linked to HRAS
• Acute myeloid leukemia, also linked to PTPN11
• LEOPARD syndrome 1, also linked to PTPN11
• Malignant tumor of urinary bladder, also linked to HRAS
• Costello syndrome, also linked to HRAS
• Dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, also linked to PIEZO1
• Metachondromatosis, also linked to PTPN11
• Juvenile myelomonocytic leukemia, also linked to PTPN11
• Monogenic short statue, also linked to PTPN11

Frequently asked questions

Which genes are linked to Non-immune hydrops fetalis?

In CATVariant, Non-immune hydrops fetalis is linked to 3 analyzed proteins: PIEZO1 (Piezo-type mechanosensitive ion channel component 1), HRAS (GTPase HRas) and PTPN11 (Tyrosine-protein phosphatase non-receptor type 11).

How many genetic variants are linked to Non-immune hydrops fetalis?

13 variants: 4 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 3 are of uncertain significance or have conflicting reports.

Which uncertain variants in Non-immune 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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