NK-cell enteropathy: genes and variants
NK-cell enteropathy is linked to 6 analyzed proteins (AURKB, AXL, CUL3, ERBB4, PIK3CB and SMARCB1). 7 DNA variants are known to cause it; 0 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 NK-cell enteropathy
AURKB: Aurora kinase B
It controls chromosome alignment, kinetochore-microtubule attachment, the spindle checkpoint, and cytokinesis as part of the chromosomal passenger complex. Excess activity is common in proliferative cancers and can contribute to aneuploidy and treatment resistance.
2 disease-causing and 0 uncertain variants in AURKB are linked to NK-cell enteropathy.
AXL: Tyrosine-protein kinase receptor UFO
Activation by GAS6 promotes cell survival, migration, immune modulation, and resistance to cellular stress. Persistent signaling is common in advanced cancers and can support epithelial-to-mesenchymal transition, metastasis, and resistance to targeted or immune therapies.
1 disease-causing and 0 uncertain variants in AXL are linked to NK-cell enteropathy.
CUL3: Cullin-3
It serves as a scaffold for multiple ubiquitin-ligase complexes that control degradation of signaling and regulatory proteins, including components of the KEAP1-NRF2 pathway. Pathogenic variants can cause pseudohypoaldosteronism type II and neurodevelopmental disorders, while somatic alterations affect cancer signaling.
1 disease-causing and 0 uncertain variants in CUL3 are linked to NK-cell enteropathy.
ERBB4: Receptor tyrosine-protein kinase erbB-4
It transduces neuregulin and other EGF-family signals important for neural, cardiac, and mammary development. Altered signaling or somatic variants occur in several cancers and have also been studied in neurodevelopmental disease.
1 disease-causing and 0 uncertain variants in ERBB4 are linked to NK-cell enteropathy.
PIK3CB: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform
It generates PIP3 downstream of growth-factor and G-protein-coupled receptors, activating AKT and other signaling pathways that regulate survival and metabolism. Some PTEN-deficient tumors become particularly dependent on p110beta activity, making it a therapeutic target.
1 disease-causing and 0 uncertain variants in PIK3CB are linked to NK-cell enteropathy.
SMARCB1: SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1
Within SWI/SNF complexes, it constrains oncogenic transcription and supports normal chromatin regulation. Biallelic tumor-cell inactivation is characteristic of malignant rhabdoid tumors, while germline variants predispose to rhabdoid tumors or schwannomatosis.
1 disease-causing and 0 uncertain variants in SMARCB1 are linked to NK-cell enteropathy.
Known disease-causing variants in NK-cell enteropathy
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| AXL L721V | 721 | Protein kinase | Disease-causing |
| ERBB4 C262Y | 262 | Extracellular | Disease-causing |
| PIK3CB E987D | 987 | PI3K/PI4K catalytic | Disease-causing |
| AURKB R283C | 283 | Protein kinase | Disease-causing |
| CUL3 G500D | 500 | Disease-causing | |
| SMARCB1 R377G | 377 | Disease-causing | |
| AURKB R284C | 284 | Protein kinase | Disease-causing |
Same protein, different disease
- Pseudohypoaldosteronism type 2E is also caused by CUL3 variants; they fall mostly in different places as the NK-cell enteropathy variants (7 disease-causing).
- Neurodevelopmental disorder with or without autism or seizures is also caused by CUL3 variants; they fall mostly in different places as the NK-cell enteropathy variants (3 disease-causing).
Diseases related to NK-cell enteropathy
- Alzheimer disease, also linked to AURKB and AXL
- Parkinson disease, also linked to AURKB and AXL
- Amyotrophic lateral sclerosis, also linked to ERBB4
- Acute myeloid leukemia, also linked to AXL
- Non-small cell lung carcinoma, also linked to ERBB4
- Coffin-Siris syndrome, also linked to SMARCB1
- Rhabdoid tumor predisposition syndrome 2, also linked to SMARCB1
- Pseudohypoaldosteronism type 2E, also linked to CUL3
- Neurodevelopmental disorder with or without autism or seizures, also linked to CUL3
Frequently asked questions
Which genes are linked to NK-cell enteropathy?
In CATVariant, NK-cell enteropathy is linked to 6 analyzed proteins: AURKB (Aurora kinase B), AXL (Tyrosine-protein kinase receptor UFO), CUL3 (Cullin-3), ERBB4 (Receptor tyrosine-protein kinase erbB-4), PIK3CB (Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform) and SMARCB1 (SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1).
How many genetic variants are linked to NK-cell enteropathy?
7 variants: 7 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 0 are of uncertain significance or have conflicting reports.
Which uncertain variants in NK-cell enteropathy look disease-causing?
None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.
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.
Download every variant as CSV · Browse all diseases · Methods · About the Center