Blau syndrome: genes and variants
Blau syndrome is linked to 1 analyzed protein (NOD2). 12 DNA variants are known to cause it; 141 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 Blau syndrome
NOD2: Nucleotide-binding oligomerization domain-containing protein 2
It detects bacterial muramyl dipeptide in the cytosol and activates antimicrobial and inflammatory responses. Common loss-of-function variants strongly increase Crohn-disease susceptibility, whereas distinct gain-of-function variants cause Blau syndrome.
12 disease-causing and 141 uncertain variants in NOD2 are linked to Blau syndrome.
Where Blau syndrome variants cluster
- NOD2 NACHT (positions 293–618): 11 of 12 disease-causing changes, 2.9× more than its size predicts.
Known disease-causing variants in Blau syndrome
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| NOD2 R334Q | 334 | NACHT | Disease-causing (★★) |
| NOD2 R334W | 334 | NACHT | Disease-causing (★★) |
| NOD2 N670K | 670 | Disease-causing (★★) | |
| NOD2 M513T | 513 | NACHT | Disease-causing (★★) |
| NOD2 R587C | 587 | NACHT | Disease-causing (★★) |
| NOD2 E383K | 383 | NACHT | Disease-causing (★) |
| NOD2 E383D | 383 | NACHT | Disease-causing (★) |
| NOD2 D382E | 382 | NACHT | Disease-causing (★) |
| NOD2 G481D | 481 | NACHT | Disease-causing (★) |
| NOD2 C495Y | 495 | NACHT | Disease-causing (★) |
| NOD2 L469F | 469 | NACHT | Disease-causing |
| NOD2 H496L | 496 | NACHT | Disease-causing |
Which prediction tools work for Blau syndrome
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- MetaLR: 98 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 94 out of 100
- PolyPhen-2: 88 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- EVE: 84 out of 100
- SIFT: 78 out of 100
Diseases related to Blau syndrome
- Autoinflammatory syndrome, also linked to NOD2
- Regional enteritis, also linked to NOD2
- Inflammatory bowel disease, also linked to NOD2
Frequently asked questions
Which genes are linked to Blau syndrome?
In CATVariant, Blau syndrome is linked to 1 analyzed protein: NOD2 (Nucleotide-binding oligomerization domain-containing protein 2).
How many genetic variants are linked to Blau syndrome?
181 variants: 12 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 141 are of uncertain significance or have conflicting reports.
Which uncertain variants in Blau 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 Blau syndrome?
Among tools not trained on clinical labels, AlphaMissense separates this disease's known disease-causing variants from harmless ones best (AUROC 0.94, based on 11 disease-causing and 16 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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