Melorheostosis: genes and variants
Melorheostosis is linked to 1 analyzed protein (MAP2K1). 2 DNA variants are known to cause it; 12 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 Melorheostosis
MAP2K1: Dual specificity mitogen-activated protein kinase kinase 1
It phosphorylates ERK1 and ERK2 downstream of RAF and thereby propagates RAS-MAPK growth and developmental signals. Activating somatic variants occur in several cancers, while germline activating variants can cause cardio-facio-cutaneous syndrome and related RASopathies.
2 disease-causing and 12 uncertain variants in MAP2K1 are linked to Melorheostosis.
Known disease-causing variants in Melorheostosis
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| MAP2K1 K57N | 57 | Disease-causing (★★) | |
| MAP2K1 K57E | 57 | Disease-causing |
Same protein, different disease
- RASopathy is also caused by MAP2K1 variants; they fall mostly in different places as the Melorheostosis variants (14 disease-causing).
- Cardiofaciocutaneous syndrome is also caused by MAP2K1 variants; they fall mostly in different places as the Melorheostosis variants (14 disease-causing).
- Cardio-facio-cutaneous syndrome is also caused by MAP2K1 variants; they fall mostly in different places as the Melorheostosis variants (6 disease-causing).
Diseases related to Melorheostosis
- Hypertrophic cardiomyopathy, also linked to MAP2K1
- RASopathy, also linked to MAP2K1
- Noonan syndrome, also linked to MAP2K1
- Noonan syndrome and Noonan-related syndrome, also linked to MAP2K1
- Neurofibromatosis, also linked to MAP2K1
- Cardiofaciocutaneous syndrome, also linked to MAP2K1
- Cardio-facio-cutaneous syndrome, also linked to MAP2K1
- Non-small cell lung carcinoma, also linked to MAP2K1
- Costello syndrome, also linked to MAP2K1
- Vascular malformation, also linked to MAP2K1
- Male infertility with azoospermia or oligozoospermia due to single gene mutation, also linked to MAP2K1
- Noonan syndrome with multiple lentigines, also linked to MAP2K1
Frequently asked questions
Which genes are linked to Melorheostosis?
In CATVariant, Melorheostosis is linked to 1 analyzed protein: MAP2K1 (Dual specificity mitogen-activated protein kinase kinase 1).
How many genetic variants are linked to Melorheostosis?
19 variants: 2 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 12 are of uncertain significance or have conflicting reports.
Which uncertain variants in Melorheostosis 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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