FOXG1 disorder: genes and variants

Genes linked to FOXG1 disorder

• FOXG1: Forkhead box protein G1

  It controls forebrain progenitor proliferation, neuronal differentiation, and cortical patterning during embryonic development. Haploinsufficiency or dysregulating variants cause FOXG1 syndrome, characterized by severe developmental impairment, absent or limited speech, abnormal movements, and frequent epilepsy.

  70 disease-causing and 124 uncertain variants in FOXG1 are linked to FOXG1 disorder.

Where FOXG1 disorder variants cluster

• FOXG1 Fork-head (positions 181–275): 68 of 70 disease-causing changes, 5.0× more than its size predicts.

Known disease-causing variants in FOXG1 disorder

Showing 60 of 70.

Uncertain variants in FOXG1 disorder that look disease-causing

Which prediction tools work for FOXG1 disorder

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

• AlphaMissense: 100 out of 100
• EVE: 100 out of 100
• MetaLR: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• MutPred2: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• PolyPhen-2: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 92 out of 100

Diseases related to FOXG1 disorder

• Rett syndrome, also linked to FOXG1
• Microcephaly, also linked to FOXG1

Frequently asked questions

Which genes are linked to FOXG1 disorder?

In CATVariant, FOXG1 disorder is linked to 1 analyzed protein: FOXG1 (Forkhead box protein G1).

How many genetic variants are linked to FOXG1 disorder?

288 variants: 70 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 124 are of uncertain significance or have conflicting reports.

Which uncertain variants in FOXG1 disorder look disease-causing?

5 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example FOXG1 N227K, FOXG1 S185T, FOXG1 N227D, FOXG1 S185G and FOXG1 V264A. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for FOXG1 disorder?

Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 1.00, based on 58 disease-causing and 15 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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