Nonpapillary renal cell carcinoma: genes and variants
Nonpapillary renal cell carcinoma is linked to 3 analyzed proteins (HNF1B, VHL and FLCN). 5 DNA variants are known to cause it; 125 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 Nonpapillary renal cell carcinoma
HNF1B: Hepatocyte nuclear factor 1-beta
It controls developmental and metabolic gene programs in kidney, pancreas, liver, and genital tract. Haploinsufficiency or intragenic pathogenic variants cause a multisystem disorder often featuring renal cysts or malformations, maturity-onset diabetes of the young, hypomagnesemia, and genital abnormalities.
4 disease-causing and 48 uncertain variants in HNF1B are linked to Nonpapillary renal cell carcinoma.
VHL: von Hippel-Lindau disease tumor suppressor
It targets hydroxylated HIF-alpha proteins for ubiquitin-mediated degradation when oxygen is sufficient, keeping hypoxia-response programs suppressed. Loss of function stabilizes HIF signaling and causes von Hippel-Lindau tumor-predisposition syndrome while also driving most clear-cell renal carcinomas.
1 disease-causing and 18 uncertain variants in VHL are linked to Nonpapillary renal cell carcinoma.
FLCN: Folliculin
It couples lysosomal nutrient sensing to AMPK, mTOR, and related pathways and helps regulate cell growth and metabolism. Germline loss-of-function variants cause Birt-Hogg-Dube syndrome with fibrofolliculomas, pulmonary cysts, pneumothorax, and renal-tumor predisposition.
0 disease-causing and 59 uncertain variants in FLCN are linked to Nonpapillary renal cell carcinoma.
Weakly linked (only a few uncertain records): SLC22A8.
Known disease-causing variants in Nonpapillary renal cell carcinoma
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| HNF1B S148L | 148 | POU-specific atypical | Disease-causing (★★) |
| HNF1B R165H | 165 | POU-specific atypical | Disease-causing (★★) |
| HNF1B R276Q | 276 | Homeobox | Disease-causing (★★) |
| HNF1B N289D | 289 | Homeobox | Disease-causing (★★) |
| VHL E70K | 70 | Disease-causing (★★) |
Same protein, different disease
- Renal cysts and diabetes syndrome is also caused by HNF1B variants; they fall mostly in different places as the Nonpapillary renal cell carcinoma variants (71 disease-causing).
- Maturity-onset diabetes of the young is also caused by HNF1B variants; they fall mostly in different places as the Nonpapillary renal cell carcinoma variants (4 disease-causing).
- Von Hippel-Lindau syndrome is also caused by VHL variants; they fall mostly in different places as the Nonpapillary renal cell carcinoma variants (147 disease-causing).
- Chuvash polycythemia is also caused by VHL variants; they fall mostly in different places as the Nonpapillary renal cell carcinoma variants (116 disease-causing).
- Pheochromocytoma is also caused by VHL variants; they fall mostly in different places as the Nonpapillary renal cell carcinoma variants (4 disease-causing).
Diseases related to Nonpapillary renal cell carcinoma
- Monogenic diabetes, also linked to HNF1B
- Von Hippel-Lindau syndrome, also linked to VHL
- Chuvash polycythemia, also linked to VHL
- Maturity-onset diabetes of the young, also linked to HNF1B
- Pheochromocytoma, also linked to VHL
- Renal cysts and diabetes syndrome, also linked to HNF1B
- Ovarian cancer, also linked to FLCN
- Type 2 diabetes mellitus, also linked to HNF1B
- Colorectal cancer, also linked to FLCN
- Birt-Hogg-Dube syndrome, also linked to FLCN
- Inherited phaeochromocytoma and paraganglioma excluding NF1, also linked to VHL
- Diabetes mellitus, also linked to HNF1B
Frequently asked questions
Which genes are linked to Nonpapillary renal cell carcinoma?
In CATVariant, Nonpapillary renal cell carcinoma is linked to 3 analyzed proteins: HNF1B (Hepatocyte nuclear factor 1-beta), VHL (von Hippel-Lindau disease tumor suppressor) and FLCN (Folliculin).
How many genetic variants are linked to Nonpapillary renal cell carcinoma?
143 variants: 5 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 125 are of uncertain significance or have conflicting reports.
Which uncertain variants in Nonpapillary renal cell carcinoma 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.
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