Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language: genes and variants

Genes linked to Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language

• MEF2C: Myocyte-specific enhancer factor 2C

  It regulates activity-dependent and developmental gene programs in neurons, muscle, immune cells, and the cardiovascular system. Haploinsufficiency causes MEF2C-related neurodevelopmental disorder, typically with severe speech impairment, intellectual disability, epilepsy, and stereotypic movements.

  24 disease-causing and 100 uncertain variants in MEF2C are linked to Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language.

Where Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language variants cluster

• MEF2C MADS-box (positions 3–57): 20 of 24 disease-causing changes, 7.2× more than its size predicts.
• MEF2C Mef2-type (positions 58–86): 3 of 24 disease-causing changes, 2.0× more than its size predicts.

Known disease-causing variants in Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language

Which prediction tools work for Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 84 out of 100
• PolyPhen-2: 77 out of 100 (learned from overlapping clinical labels, so this is optimistic)

Frequently asked questions

Which genes are linked to Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language?

In CATVariant, Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language is linked to 1 analyzed protein: MEF2C (Myocyte-specific enhancer factor 2C).

How many genetic variants are linked to Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language?

158 variants: 24 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 100 are of uncertain significance or have conflicting reports.

Which uncertain variants in Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.84, based on 18 disease-causing and 19 harmless variants).

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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