X-linked severe congenital neutropenia: genes and variants
X-linked severe congenital neutropenia is linked to 1 analyzed protein (WAS). 22 DNA variants are known to cause it; 148 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 X-linked severe congenital neutropenia
WAS: Actin nucleation-promoting factor WAS
It couples signaling from immune receptors to actin-cytoskeleton remodeling, enabling immune synapse formation, cell migration, and normal platelet production. Loss-of-function variants cause Wiskott-Aldrich syndrome or X-linked thrombocytopenia, while activating variants can cause severe congenital neutropenia.
22 disease-causing and 148 uncertain variants in WAS are linked to X-linked severe congenital neutropenia.
Where X-linked severe congenital neutropenia variants cluster
- WAS WH1 (positions 39–148): 16 of 22 disease-causing changes, 3.3× more than its size predicts.
Known disease-causing variants in X-linked severe congenital neutropenia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| WAS R86H | 86 | WH1 | Disease-causing (★★) |
| WAS R86C | 86 | WH1 | Disease-causing (★★) |
| WAS F128S | 128 | WH1 | Disease-causing (★★) |
| WAS T45M | 45 | WH1 | Disease-causing (★★) |
| WAS E31K | 31 | Disease-causing (★★) | |
| WAS L270P | 270 | Disease-causing (★★) | |
| WAS I290T | 290 | Disease-causing (★★) | |
| WAS A56V | 56 | WH1 | Disease-causing (★★) |
| WAS D224G | 224 | Disease-causing (★★) | |
| WAS F128L | 128 | WH1 | Disease-causing (★) |
| WAS F128C | 128 | WH1 | Disease-causing (★) |
| WAS E133D | 133 | WH1 | Disease-causing (★) |
| WAS A134V | 134 | WH1 | Disease-causing (★) |
| WAS F84L | 84 | WH1 | Disease-causing (★) |
| WAS G125R | 125 | WH1 | Disease-causing (★) |
| WAS S24P | 24 | Disease-causing (★) | |
| WAS T48P | 48 | WH1 | Disease-causing (★) |
| WAS W64R | 64 | WH1 | Disease-causing (★) |
| WAS S272P | 272 | Disease-causing (★) | |
| WAS L101P | 101 | WH1 | Disease-causing (★) |
| WAS Y107H | 107 | WH1 | Disease-causing (★) |
| WAS P58T | 58 | WH1 | Disease-causing (★) |
Which prediction tools work for X-linked severe congenital neutropenia
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- CATVariant: 100 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- PolyPhen-2: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 97 out of 100
Same protein, different disease
- Wiskott-Aldrich syndrome is also caused by WAS variants; they fall partly in the same places as the X-linked severe congenital neutropenia variants (28 disease-causing).
Diseases related to X-linked severe congenital neutropenia
- Wiskott-Aldrich syndrome, also linked to WAS
Frequently asked questions
Which genes are linked to X-linked severe congenital neutropenia?
In CATVariant, X-linked severe congenital neutropenia is linked to 1 analyzed protein: WAS (Actin nucleation-promoting factor WAS).
How many genetic variants are linked to X-linked severe congenital neutropenia?
210 variants: 22 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 148 are of uncertain significance or have conflicting reports.
Which uncertain variants in X-linked severe congenital neutropenia 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 X-linked severe congenital neutropenia?
Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.97, based on 21 disease-causing and 21 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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