Familial pulmonary capillary hemangiomatosis: genes and variants
Familial pulmonary capillary hemangiomatosis is linked to 1 analyzed protein (EIF2AK4). 9 DNA variants are known to cause it; 10 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 Familial pulmonary capillary hemangiomatosis
EIF2AK4: eIF-2-alpha kinase GCN2
It senses amino-acid deprivation and other stresses and reduces global translation through phosphorylation of eIF2alpha. Biallelic loss-of-function variants are a major cause of pulmonary capillary hemangiomatosis and pulmonary veno-occlusive disease.
9 disease-causing and 9 uncertain variants in EIF2AK4 are linked to Familial pulmonary capillary hemangiomatosis.
Weakly linked (only a few uncertain records): BMPR2.
Where Familial pulmonary capillary hemangiomatosis variants cluster
- EIF2AK4 Protein kinase 2 (positions 590–1001): 4 of 9 disease-causing changes, 1.8× more than its size predicts.
- EIF2AK4 Histidyl-tRNA synthetase-like (positions 1022–1493): 4 of 9 disease-causing changes, 1.6× more than its size predicts.
Known disease-causing variants in Familial pulmonary capillary hemangiomatosis
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| EIF2AK4 R585Q | 585 | Disease-causing (★) | |
| EIF2AK4 G599R | 599 | Protein kinase 2 | Disease-causing |
| EIF2AK4 L643R | 643 | Protein kinase 2 | Disease-causing |
| EIF2AK4 H1202L | 1202 | Histidyl-tRNA synthetase-like | Disease-causing |
| EIF2AK4 V607G | 607 | Protein kinase 2 | Disease-causing |
| EIF2AK4 S909R | 909 | Protein kinase 2 | Disease-causing |
| EIF2AK4 G1109R | 1109 | Histidyl-tRNA synthetase-like | Disease-causing |
| EIF2AK4 P1115L | 1115 | Histidyl-tRNA synthetase-like | Disease-causing |
| EIF2AK4 L1295R | 1295 | Histidyl-tRNA synthetase-like | Disease-causing |
Which prediction tools work for Familial pulmonary capillary hemangiomatosis
How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).
- PolyPhen-2: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- SIFT: 92 out of 100
- CATVariant: 85 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Diseases related to Familial pulmonary capillary hemangiomatosis
- Pulmonary arterial hypertension, also linked to EIF2AK4
Frequently asked questions
Which genes are linked to Familial pulmonary capillary hemangiomatosis?
In CATVariant, Familial pulmonary capillary hemangiomatosis is linked to 1 analyzed protein: EIF2AK4 (eIF-2-alpha kinase GCN2).
How many genetic variants are linked to Familial pulmonary capillary hemangiomatosis?
25 variants: 9 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 10 are of uncertain significance or have conflicting reports.
Which uncertain variants in Familial pulmonary capillary hemangiomatosis 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 Familial pulmonary capillary hemangiomatosis?
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 78 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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