Frontometaphyseal dysplasia: genes and variants

Genes linked to Frontometaphyseal dysplasia

• FLNA: Filamin-A

  It crosslinks actin and connects the cytoskeleton to membrane receptors and signaling proteins during cell migration and tissue morphogenesis. Pathogenic variants cause a broad spectrum including periventricular nodular heterotopia and several skeletal or connective-tissue disorders.

  12 disease-causing and 713 uncertain variants in FLNA are linked to Frontometaphyseal dysplasia.

Where Frontometaphyseal dysplasia variants cluster

• FLNA Filamin 10 (positions 1155–1249): 4 of 12 disease-causing changes, 9.3× more than its size predicts.
• FLNA Actin-binding (positions 2–274): 4 of 12 disease-causing changes, 3.2× more than its size predicts.

Known disease-causing variants in Frontometaphyseal dysplasia

Which prediction tools work for Frontometaphyseal dysplasia

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

• CATVariant: 81 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 79 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 71 out of 100

Same protein, different disease

• Oto-palato-digital syndrome, type II is also caused by FLNA variants; they fall mostly in different places as the Frontometaphyseal dysplasia variants (14 disease-causing).
• Heterotopia, periventricular, X-linked dominant is also caused by FLNA variants; they fall mostly in different places as the Frontometaphyseal dysplasia variants (14 disease-causing).
• Melnick-Needles syndrome is also caused by FLNA variants; they fall mostly in different places as the Frontometaphyseal dysplasia variants (8 disease-causing).
• Cardiac valvular dysplasia, X-linked is also caused by FLNA variants; they fall mostly in different places as the Frontometaphyseal dysplasia variants (4 disease-causing).

Diseases related to Frontometaphyseal dysplasia

• Familial thoracic aortic aneurysm and aortic dissection, also linked to FLNA
• Connective tissue disorder, also linked to FLNA
• Heterotopia, periventricular, X-linked dominant, also linked to FLNA
• Oto-palato-digital syndrome, type II, also linked to FLNA
• Melnick-Needles syndrome, also linked to FLNA
• Periventricular nodular heterotopia, also linked to FLNA
• FG syndrome, also linked to FLNA
• Cardiac valvular dysplasia, X-linked, also linked to FLNA

Frequently asked questions

Which genes are linked to Frontometaphyseal dysplasia?

In CATVariant, Frontometaphyseal dysplasia is linked to 1 analyzed protein: FLNA (Filamin-A).

How many genetic variants are linked to Frontometaphyseal dysplasia?

891 variants: 12 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 713 are of uncertain significance or have conflicting reports.

Which uncertain variants in Frontometaphyseal dysplasia 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 Frontometaphyseal dysplasia?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.71, based on 8 disease-causing and 216 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.

Download every variant as CSV · Browse all diseases · Methods · About the Center