Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome: genes and variants
Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome is linked to 1 analyzed protein (TBCD). 10 DNA variants are known to cause it; 59 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 Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome
TBCD: Tubulin-specific chaperone D
A tubulin-folding chaperone that helps assemble tubulin complexes and regulate microtubule dynamics. It also acts as a regulator of the ARL2 GTPase and supports mitotic-spindle formation and neuronal morphogenesis.
10 disease-causing and 59 uncertain variants in TBCD are linked to Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome.
Known disease-causing variants in Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| TBCD A475T | 475 | Disease-causing (★★) | |
| TBCD H77R | 77 | Disease-causing (★★) | |
| TBCD A554V | 554 | Disease-causing (★★) | |
| TBCD R772C | 772 | Disease-causing (★★) | |
| TBCD R502G | 502 | Disease-causing (★) | |
| TBCD P693T | 693 | Disease-causing (★) | |
| TBCD M387R | 387 | HEAT 1 | Disease-causing |
| TBCD R377Q | 377 | HEAT 1 | Disease-causing |
| TBCD A921T | 921 | Disease-causing | |
| TBCD P937R | 937 | Disease-causing |
Which prediction tools work for Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 92 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 90 out of 100
Frequently asked questions
Which genes are linked to Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome?
In CATVariant, Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome is linked to 1 analyzed protein: TBCD (Tubulin-specific chaperone D).
How many genetic variants are linked to Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome?
91 variants: 10 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 59 are of uncertain significance or have conflicting reports.
Which uncertain variants in Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome 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 Early-onset progressive diffuse brain atrophy-microcephaly-muscle weakness-optic atrophy syndrome?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.90, based on 10 disease-causing and 30 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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