Hereditary diffuse leukoencephalopathy with spheroids: genes and variants
Hereditary diffuse leukoencephalopathy with spheroids is linked to 1 analyzed protein (CSF1R). 9 DNA variants are known to cause it; 28 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 Hereditary diffuse leukoencephalopathy with spheroids
CSF1R: Macrophage colony-stimulating factor 1 receptor
Signals from CSF1 and IL-34 through this pathway are required for development, survival, and function of macrophages and microglia. Pathogenic variants can cause adult-onset leukoencephalopathy with cognitive, psychiatric, and motor deterioration.
9 disease-causing and 28 uncertain variants in CSF1R are linked to Hereditary diffuse leukoencephalopathy with spheroids.
Where Hereditary diffuse leukoencephalopathy with spheroids variants cluster
- CSF1R Protein kinase (positions 582–910): 9 of 9 disease-causing changes, 3.0× more than its size predicts.
Known disease-causing variants in Hereditary diffuse leukoencephalopathy with spheroids
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| CSF1R A781V | 781 | Protein kinase | Disease-causing (★★) |
| CSF1R G591E | 591 | Protein kinase | Disease-causing (★★) |
| CSF1R I794T | 794 | Protein kinase | Disease-causing (★★) |
| CSF1R A823T | 823 | Protein kinase | Disease-causing (★) |
| CSF1R T833K | 833 | Protein kinase | Disease-causing (★) |
| CSF1R A781E | 781 | Protein kinase | Disease-causing |
| CSF1R A823V | 823 | Protein kinase | Disease-causing |
| CSF1R F828S | 828 | Protein kinase | Disease-causing |
| CSF1R D837Y | 837 | Protein kinase | Disease-causing |
Which prediction tools work for Hereditary diffuse leukoencephalopathy with spheroids
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 92 out of 100
Same protein, different disease
- Leukoencephalopathy, diffuse hereditary, with spheroids 1 is also caused by CSF1R variants; they fall partly in the same places as the Hereditary diffuse leukoencephalopathy with spheroids variants (13 disease-causing).
Diseases related to Hereditary diffuse leukoencephalopathy with spheroids
- Alzheimer disease, also linked to CSF1R
- Gastrointestinal stromal tumor, also linked to CSF1R
- Leukoencephalopathy, diffuse hereditary, with spheroids 1, also linked to CSF1R
- Renal cell carcinoma, also linked to CSF1R
- Brain abnormalities, neurodegeneration, and dysosteosclerosis, also linked to CSF1R
Frequently asked questions
Which genes are linked to Hereditary diffuse leukoencephalopathy with spheroids?
In CATVariant, Hereditary diffuse leukoencephalopathy with spheroids is linked to 1 analyzed protein: CSF1R (Macrophage colony-stimulating factor 1 receptor).
How many genetic variants are linked to Hereditary diffuse leukoencephalopathy with spheroids?
68 variants: 9 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 28 are of uncertain significance or have conflicting reports.
Which uncertain variants in Hereditary diffuse leukoencephalopathy with spheroids 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 Hereditary diffuse leukoencephalopathy with spheroids?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.92, based on 9 disease-causing and 69 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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