Congenital hypothalamic hamartoma syndrome: genes and variants
Congenital hypothalamic hamartoma syndrome is linked to 1 analyzed protein (SMO). 6 DNA variants are known to cause it; 17 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 Congenital hypothalamic hamartoma syndrome
SMO: Protein smoothened
It transmits Hedgehog signals across the membrane after inhibition by PTCH1 is relieved, activating GLI-dependent developmental transcription. Activating variants or upstream pathway loss can drive basal-cell carcinoma, medulloblastoma, and other Hedgehog-dependent tumors.
6 disease-causing and 17 uncertain variants in SMO are linked to Congenital hypothalamic hamartoma syndrome.
Known disease-causing variants in Congenital hypothalamic hamartoma syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| SMO R400C | 400 | Transmembrane | Disease-causing (★) |
| SMO R576W | 576 | Required for interaction with PRKACA | Disease-causing (★) |
| SMO F252L | 252 | Transmembrane | Disease-causing (★) |
| SMO R576Q | 576 | Required for interaction with PRKACA | Disease-causing |
| SMO R261C | 261 | Cytoplasmic | Disease-causing |
| SMO I429F | 429 | Cytoplasmic | Disease-causing |
Diseases related to Congenital hypothalamic hamartoma syndrome
- Acute myeloid leukemia, also linked to SMO
- Medulloblastoma, also linked to SMO
- Basal cell carcinoma, also linked to SMO
- Curry-Jones syndrome, also linked to SMO
Frequently asked questions
Which genes are linked to Congenital hypothalamic hamartoma syndrome?
In CATVariant, Congenital hypothalamic hamartoma syndrome is linked to 1 analyzed protein: SMO (Protein smoothened).
How many genetic variants are linked to Congenital hypothalamic hamartoma syndrome?
29 variants: 6 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 17 are of uncertain significance or have conflicting reports.
Which uncertain variants in Congenital hypothalamic hamartoma 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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